pituitrin and Diabetes-Mellitus--Type-2

Arginine vasopressin (AVP), which is also called antidiuretic hormone (ADH), is a neurohormone synthetized from a pre-pro-hormone precursor in the supraoptic and paraventricular nuclei of the hypothalamus in response to increased plasma osmolality and decreased blood volume. AVP exerts several effects by binding to three different receptors: V1aR, V1bR, and V2R. In recent years, it has been suggested that increased plasma concentration of AVP may play a causal role in the development of type 2 diabetes, the metabolic syndrome, renal dysfunction and cardiovascular disease by influencing glucose homeostasis and lipid metabolism through several possible mechanisms involving V1aR and V1bR. V1aR located in the liver is involved in hepatic glycogenolysis and gluconeogenesis. V1bR, found in the pituitary gland and pancreas, mediates secretion of adrenocorticotrophic hormone (ACTH), insulin, and glucagon. However, AVP's clinical use as a biomarker is limited due to its short half-life in plasma (16-20 minutes), small size, and poor stability, which make direct measurement difficult. Copeptin, the biologically inactive, stable, C-terminal part of pro-vasopressin, is co-secreted with AVP in equimolar amounts and thus is considered an adequate and clinically useful surrogate marker of AVP. The aim of this review is to assess the current state of knowledge about the potential role of copeptin as a novel biomarker of cardiometabolic syndrome on the basis of recent scientific literature published up to December 2020 and searches of the PubMed, Google Scholar, and Web of Science databases.

Topics: Arginine Vasopressin; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glycopeptides; Humans; Metabolic Syndrome; Neurophysins; Predictive Value of Tests; Protein Precursors; Vasopressins

The neurohypophysial endocrine system is identified here as a potential target for therapeutic interventions toward improving obesity-related metabolic dysfunction, given its coinciding pleiotropic effects on psychological, neurological and metabolic systems that are disrupted in obesity.. Copeptin, the C-terminal portion of the precursor of arginine-vasopressin, is positively associated with body mass index and risk of type 2 diabetes. Plasma oxytocin is decreased in obesity and several other conditions of abnormal glucose homeostasis. Recent data also show non-classical tissues, such as myocytes, hepatocytes and β-cells, exhibit responses to oxytocin and vasopressin receptor binding that may contribute to alterations in metabolic function. The modulation of anorexigenic and orexigenic pathways appears to be the dominant mechanism underlying the effects of oxytocin and vasopressin on body weight regulation; however, there are apparent limitations associated with their use in direct pharmacological applications. A clearer picture of their wider physiological effects is needed before either system can be considered for therapeutic use.

Topics: Animals; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Eating; Energy Metabolism; Gastrointestinal Microbiome; Glucose; Hepatocytes; Homeostasis; Humans; Insulin Resistance; Lipid Metabolism; Muscle Cells; Obesity; Oxytocin; Vasopressins

Diabetic nephropathy has become the most common cause of chronic kidney disease (CKD). Despite the progress accomplished in therapy, the prevalence of renal disorders remains high. Some modifiable factors driving the increase in incidence of CKD, in diabetes and other settings, might have been overlooked. Consistent evidence supports a role for vasopressin, hydration state, and urine concentration in kidney health.. Plasma vasopressin is elevated in diabetes, even if metabolic control is good. Several epidemiological studies have pointed to a positive association between markers of vasopressin secretion (24-h fluid intake, urine volume, plasma copeptin concentration) and renal function decline in both the community and populations at high risk of CKD, namely, diabetic patients. Research involving animal models also supports a critical causal role of the V2 receptor antidiuretic effects of vasopressin in the early signs of kidney disease associated with type 1 or type 2 diabetes. Key Messages: Data supporting the detrimental effects of chronic vasopressin action on the kidney is consistent in animal models and human observational studies. Since vasopressin secretion can be modulated by water intake, and its actions by selective receptor antagonists, the vasopressin-hydration system could be a potential therapeutic target for the prevention and treatment of diabetic nephropathy. Intervention studies are needed to examine the relevance of lifestyle or pharmacological interventions.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Models, Animal; Drinking; Glycopeptides; Humans; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Vasopressins

In both diabetic subjects and animal models high levels of vasopressin (AVP) have beendetected. The relationship between AVP and glucose metabolism is mediated through several direct andindirect effects and most of them are still unknown.. We have reviewed 100 manuscripts retrieved from Cochrane Library, Embase and Pubmeddatabases in order to highlight a possible relationship between copeptin and type 2 diabetes and to provideinsights on the molecular mechanism that could explain this association.. AVP potentiates CRH action at pituitary level resulting in an increased ACTH secretion and in turn in an increased cortisol secretion that escapes the negative feedback loop. Further, AVP regulates insulin and glucagon secretion through V1b receptor and promotes hepatic glycogenolysis and gluconeogenesis through V1a receptor. In addition to worsen glucose metabolism, AVP has been reported to have a role in the pathogenesis of diabetic complications such as cardiovascular diseases, kidney and ocular complications. Due to the very low concentration of AVP in the blood, the small size and poor stability, the assay of AVP is very difficult to perform. Thus, copeptin, the stable C-terminal portion of the prepro-vasopressin peptide has been identified as an easier assay to be measured and that mirrors AVP activity. Although there are promising evidence that copeptin could be involved in the pathogenesis of type 2 diabetes, further studies need to demonstrate the importance of copeptin as clinical marker to predict glucose metabolism derangements.

Topics: Animals; Arginine Vasopressin; Biomarkers; Diabetes Mellitus, Type 2; Drinking; Glucagon; Glycopeptides; Humans; Insulin; Vasopressins

In diabetes mellitus (DM), the urine flow rate is increased, and the fluid turnover in the body is accelerated because of the glucose-induced osmotic diuresis. On the other hand, plasma vasopressin (VP) is elevated in both type 1 and type 2 DM. This elevation seems to be due to a resetting of the osmostat. A high VP level is beneficial in the short term because it limits to some extent the amount of water required for the excretion of a markedly enhanced load of osmoles (mainly glucose). However, in the long run, it may have adverse effects by favoring the development of diabetic nephropathy. VP has been shown in normal rats to induce kidney hypertrophy, glomerular hyperfiltration, and an increase in urinary albumin excretion (features also occurring in association in the period preceding diabetic nephropathy). Moreover, VP has been shown to participate in the progression of renal failure in rats with five-sixths reduction in renal mass. In recent studies, we have shown (1) that creatinine clearance, albuminuria and renal mass increased much less during experimental DM in Brattleboro rats unable to secrete VP than in their VP-replete Long-Evans controls, and (2) that albuminuria was prevented during experimental DM in Wistar rats when a VP nonpeptidic, highly selective V2 receptor antagonist was administered chronically for 9 weeks. Taken together, these results strongly suggest that VP plays a crucial role in the onset and aggravation of the renal complications of DM. The mechanisms by which VP exerts these adverse V2-dependent effects are not yet elucidated. They are most likely indirect and may involve several intermediate steps comprising VP-induced changes in the composition of the tubular fluid in the loop of Henle (due to solute recycling in the renal medulla associated with improved concentrating activity of the kidney), inhibition of the tubuloglomerular feedback control of glomerular function, and alterations in glomerular hemodynamics by the intrarenal renin-angiotensin system.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Vasopressins

Arterial hypertension and, less often, postural hypotension are frequently associated with diabetes mellitus, and with diabetic complications and death.. To review data on the relationship between hypertension and nephropathy in diabetes mellitus.. We reviewed data on both retinopathy and nephropathy in hypertensive diabetic patients. Data suggesting that vasopressin levels might affect blood pressure in upright patients with postural hypotension due to cardiocirculatory diabetic neuropathy were also examined. Antihypertensive treatment during different phases of diabetic nephropathy in insulin-dependent diabetes was reviewed.. The data showed that hydrochlorothiazide and nitrendipine reduce urinary protein excretion in parallel with a reduction in blood pressure. However, the decreases in urinary protein excretion induced by captopril are not correlated with a reduction in blood pressure and may be related to decreases in intraglomerular pressure found in patients with mild renal failure taking furosemide. Domperidone, a peripherally acting dopaminergic antagonist is an additional therapeutic option for the treatment of diabetic postural hypotension.

Topics: Antihypertensive Agents; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Hypertension, Renal; Hypotension, Orthostatic; Male; Vasopressins

Because elevated copeptin, a marker of vasopressin, is linked to low water intake and high diabetes risk, we tested the effect of water supplementation on copeptin and fasting glucose.. Thirty-one healthy adults with high copeptin (>10.7 pmol · L-1 in men and >6.1 pmol·L-1 in women) identified in a population-based survey from 2013 to 2015 and with a current 24-hour urine osmolality of >600 mOsm · kg-1 were included.. Addition of 1.5 L water daily on top of habitual fluid intake for 6 weeks.. Pre- and postintervention fasting plasma copeptin concentrations.. Reported mean water intake increased from 0.43 to 1.35 L · d-1 (P < 0.001), with no other observed changes in diet. Median (interquartile range) urine osmolality was reduced from 879 (705, 996) to 384 (319, 502) mOsm · kg-1 (P < 0.001); urine volume increased from 1.06 (0.90, 1.20) to 2.27 (1.52, 2.67) L · d-1 (P < 0.001); and baseline copeptin decreased from 12.9 (7.4, 21.9) pmol · L-1 to 7.8 (4.6;11.3) pmol · L-1 (P < 0.001). Water supplementation reduced fasting plasma glucose from a mean (SD) of 5.94 (0.44) to 5.74 (0.51) (P = 0.04). The water-associated reduction of both fasting copeptin and glucose concentration in plasma was most pronounced in participants in the top tertile of baseline copeptin.. Water supplementation in persons with habitually low water consumption and high copeptin levels is effective in lowering copeptin. It appears a safe and promising intervention with the potential of lowering fasting plasma glucose and thus reducing diabetes risk. Further investigations are warranted to support these findings.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drinking; Fasting; Female; Glycopeptides; Healthy Volunteers; Humans; Male; Middle Aged; Osmolar Concentration; Pilot Projects; Treatment Outcome; Urine; Vasopressins; Water; Young Adult

To investigate whether sitagliptin affects copeptin and osmolality, suggesting arginine vasopressin activation and a potential for fluid retention, compared with placebo, in patients with a recent acute coronary syndrome and newly discovered type 2 diabetes or impaired glucose tolerance. A second aim was to confirm whether copeptin correlated with insulin-like growth factor binding protein-1.. Fasting blood samples were used from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction trial, in which patients recently hospitalized due to acute coronary syndrome and with newly detected abnormal glucose tolerance were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37). Copeptin, osmolality and insulin-like growth factor binding protein-1 were analysed at baseline and after 12 weeks.. Copeptin and osmolality were unaffected by sitagliptin. There was no correlation between copeptin and insulin-like growth factor binding protein-1.. Sitagliptin therapy does not appear to be related to activation of the arginine vasopressin system.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Biomarkers; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Administration Schedule; Female; Glycopeptides; Hospitalization; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Secreting Cells; Male; Middle Aged; Myocardial Infarction; Neurophysins; Osmolar Concentration; Protein Precursors; Sitagliptin Phosphate; Sweden; Time Factors; Treatment Outcome; Vasopressins; Water-Electrolyte Balance

Statins have beneficial effects on cardiovascular morbidity and mortality independently of reduction of plasma cholesterol.. In patients with type 2 diabetes and nephropathy, chronic kidney disease stage II-III, we tested the hypothesis that atorvastatin increased systemic and renal nitric oxide (NO) availability using L-NMMA as an inhibitor of NO production. We performed a randomized, placebo-controlled, crossover study, using atorvastatin/placebo treatment for five days with a standardized diet and fluid intake. We measured brachial BP (bBP), central BP (cBP), GFR, urinary output (OU), free water clearance (CH2O), fractional excretion of sodium (FENa), urinary excretion of albumin (UAER and UACR), AQP2 (u-AQP2) and ENaC (u-ENaCγ) and plasma concentrations of vasoactive hormones: renin, angiotensin II, aldosterone, arginine vasopressin, endothelin-1 and brain natriuretic peptide.. During atorvastatin and placebo treatment, L-NMMA infusion, changed the effect variables significantly, but to the same extent, i.e. an increase in bBP and cBP, and a decrease in GFR, OU, CH2O, FENa, u-AQP2 and u-ENaCγ. In addition, renin and angiotensin II was reduced, aldosterone increased, and vasopressin, endothelin-1 and brain natriuretic hormone unchanged.. During, atorvastatin and placebo treatment, inhibition of nitric oxide synthesis induced the same response in brachial and central blood pressure, GFR, renal tubular function and vasoactive hormones. Thus, atorvastatin did not change nitric oxide availability in type 2 diabetics with nephropathy.

Topics: Aged; Arginine Vasopressin; Atorvastatin; Atrial Natriuretic Factor; Blood Pressure; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glomerular Filtration Rate; Heart Rate; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Tubules; Male; Middle Aged; Natriuretic Peptide, Brain; Nitric Oxide; omega-N-Methylarginine; Pulse Wave Analysis; Pyrroles; Renal Insufficiency, Chronic; Treatment Outcome; Vascular Stiffness; Vasopressins

Short sleep is linked to disturbances in glucose metabolism and may induce a prediabetic condition. The biological clock in the suprachiasmatic nucleus (SCN) regulates the glucose rhythm in the circulation and the sleep-wake cycle. SCN vasopressin neurons (SCN

Topics: Animals; Circadian Rhythm; Diabetes Mellitus, Type 2; Glucose; Glucose Transporter Type 1; Hyperglycemia; Rats; Sleep; Suprachiasmatic Nucleus; Vasopressins

Arginine vasopressin (AVP) plays an important role in the pathophysiology of Diabetes Mellitus (DM) and its related complications like diabetic nephropathy. Copeptin is considered as a reliable surrogate biomarker of AVP. If raised levels of copeptin in diabetic patients are detected earlier, prognosis of DM can be improved by timely modulating the treatment strategy.. The study is therefore planned to assess copeptin levels in different groups of DM and in healthy controls to suggest a better and reliable biomarker for progressive stages of DM.. Subjects were recruited as controls, pre diabetes, DM without nephropathy and diabetic nephropathy. Serum copeptin levels were measured by ELISA. While, Blood Urea Nitrogen (BUN), creatinine, Glycosylated Hemoglobin (HbA1c) and spot urinary albumin creatinine ratio (UACR) were done using spectrophotometry. Statistical analysis was done using ANOVA and Pearson's correlation tests on SPSS.. The average copeptin levels were 215.096 pg/mL. Copeptin levels were significantly elevated in subjects with positive family history of DM (p = 0.025), levels were also raised in pre diabetes kpatients (252.85 pg/mL) as compared to other groups. Copeptin levels were also correlated with HbA1c r = 0.171 (p = 0.101), BUN r = 0.244 (p = 0.007), creatinine r = 0.215 (p = 0.018), UACR r = 0.375 (p = <0.001) and GFR r = 0.215 (p = <0.019).. The significant correlation of copeptin with diabetic and renal biomarkers, along with its positive association with family history of DM support its' role as an early and reliable biomarker of DM and its associated nephropathy.

Topics: Adolescent; Adult; Aged; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycopeptides; Humans; Kidney; Kidney Function Tests; Male; Middle Aged; Neurophysins; Prognosis; Protein Precursors; Vasopressins; Young Adult

The central pacemaker of the mammalian biological timing system is located within the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. Together with the peripheral clocks, this central brain clock ensures a timely, up-to-date and proper behaviour for an individual throughout the day-night cycle. A mismatch between the central and peripheral clocks results in a disturbance of daily rhythms in physiology and behaviour. It is known that the number of rhythmically expressed genes is reduced in peripheral tissue of individuals with type 2 diabetes mellitus. However, it is not known whether the central SCN clock is also affected in the pathogenesis of type 2 diabetes. In the current study, we compared the profiles of the SCN neurons and glial cells between type 2 diabetic and control individuals.. We collected post-mortem hypothalamic tissues from 28 type 2 diabetic individuals and 12 non-diabetic control individuals. We performed immunohistochemical analysis for three SCN neuropeptides, arginine vasopressin (AVP), vasoactive intestinal polypeptide (VIP) and neurotensin (NT), and for two proteins expressed in glial cells, ionised calcium-binding adapter molecule 1 (IBA1, a marker of microglia) and glial fibrillary acidic protein (GFAP, a marker of astroglial cells).. The numbers of AVP immunoreactive (AVP-ir) and VIP-ir neurons and GFAP-ir astroglial cells in the SCN of type 2 diabetic individuals were significantly decreased compared with the numbers in the SCN of the control individuals. In addition, the relative intensity of AVP immunoreactivity was reduced in the individuals with type 2 diabetes. The number of NT-ir neurons and IBA1-ir microglial cells in the SCN was similar in the two groups.. Our data show that type 2 diabetes differentially affects the numbers of AVP- and VIP-expressing neurons and GFAP-ir astroglial cells in the SCN, each of which could affect the daily rhythmicity of the SCN biological clock machinery. Therefore, for effectively treating type 2 diabetes, lifestyle changes and/or medication to normalise central biological clock functioning might be helpful.

Topics: Arginine Vasopressin; Circadian Rhythm; Diabetes Mellitus, Type 2; Humans; Life Style; Microglia; Neuroglia; Neurons; Neuropeptides; Neurophysins; Protein Precursors; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

Chronic kidney disease (CKD) is a leading complication of type 2 diabetes mellitus (T2DM) and is considered as a public health problem. Copeptin is a surrogate marker of arginine vasopressin (AVP) system and is proposed as a biomarker of decline renal function.. Evaluate whether plasma copeptin levels may be used as a biomarker of decline renal function in patients with T2DM.. A total of 480 patients with T2DM and different stages of CKD were included. Plasma levels of copeptin, cystatin-C, and other biochemical parameters were measured. The correlation between copeptin and glomerular filtration rate (GFR), estimated based on plasma cystatin-C levels, was investigated.. Plasma copeptin levels were gradually increased from the stage 1-5 of CKD in the patients with T2DM. In univariate linear regression analysis, high plasma levels of copeptin were associated with lower GFR (Standardized β = -0.535, R. The results show that high plasma copeptin levels are associated with the decline of renal function in patients with T2DM and, therefore, copeptin may be considered as a biomarker of renal function. Further evaluation of plasma copeptin levels to predict morbidity and mortality of T2DM patients, with or without CKD, has been taken into our consideration.

Topics: Arginine Vasopressin; Biomarkers; Cystatin C; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Glycopeptides; Humans; Male; Middle Aged; Neurophysins; Protein Precursors; Renal Insufficiency, Chronic; Vasopressins

Type 2 diabetes, chronic kidney disease (CKD) and its cardiovascular complications are increasing as health problems worldwide. These diseases are interrelated with overlapping occurrence and once diabetes is established, the risk of cardiorenal disease is dramatically elevated. Thus, a search for unifying modifiable risk factors is key for effective prevention.. Elevated fasting plasma concentration of vasopressin, measured with the marker copeptin, predicts new onset type 2 diabetes as well as renal function decline. Furthermore, we recently showed that increased plasma copeptin concentration independently predicts the development of both CKD and other specified kidney diseases. In consequence, high copeptin is an independent risk factor for cardiovascular disease and premature mortality in both diabetes patients and in the general population. Vasopressin is released when plasma osmolality is high, and the easiest way to lower plasma vasopressin and copeptin concentration is to increase water intake. In a human water intervention experiment with 1 week of 3 L/day increased water intake, the one third of the participants with the greatest copeptin reduction (water responders) were those with a phenotype of low water intake (high habitual plasma copeptin and urine osmolality, and low urine volume). The water-responders had a copeptin reduction of 41% after 1 week of increased water intake compared to a control week; in contrast, a 3% reduction occurred in the other two thirds of the study participants. Among water responders, increased water intake also induced a reduction in fasting glucagon concentration. Key Messages: Elevated copeptin, a measure of vasopressin, is a risk marker of metabolic and cardiorenal diseases and may assist in the detection of individuals at higher risk for these diseases. Furthermore, individuals with high copeptin and other signs of low water intake may experience beneficial glucometabolic effects of increased water intake. Future randomized control trials investigating effects of hydration on glucometabolic and renal outcomes should focus on individuals with signs of low water intake including high plasma copeptin concentration.

Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drinking; Glycopeptides; Humans; Life Style; Osmolar Concentration; Renal Insufficiency, Chronic; Risk Factors; Vasopressins

Acetylsalicylic acid (ASA) treatment in diabetic patients is very important owing to the increasing hyperactivity of thrombocytes and atherosclerosis. In several investigations, it was reported that diabetes caused increased coronary artery disease, cerebrovascular disease, and death. In this study, we aimed to investigate the effect of ASA on osmoregulation, glycemic control, and some biochemical parameters in rats induced with experimental diabetes type 2.. Twenty-four rats were randomly divided in four groups: control (I), ASA control (II), diabetic (III), and ASA diabetic (IV). Diabetes was induced by streptozotocin treatment (30 mg/kg, twice, intraperitoneal injection) in obese rats. ASA (150 mg/kg body weight, orally) was administered for 5 weeks in the ASA control and ASA diabetic groups. Serum electrolytes, creatinine, albumin, and total protein levels were analyzed with an autoanalyzer. Arginine vasopressin (AVP) and insulin were analyzed by ELISA techniques.. At the end of the study ASA treatments had decreased the fasting blood glucose levels but had interestingly increased the serum AVP levels in diabetics rats.. AVP levels were increased 2-fold by ASA treatment in diabetic rats. For the first time in this study, the hypoglycemic effect of ASA was attributed to an increase in blood volume by AVP levels. This explanation may be a new approach to the literature on this topic.

Topics: Animals; Aspirin; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Insulin; Insulin Resistance; Male; Osmoregulation; Random Allocation; Rats; Rats, Wistar; Vasopressins

A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metformin-associated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.

Topics: Acidosis, Lactic; Aged; Diabetes Mellitus, Type 2; Fatal Outcome; Female; Fluid Therapy; Hemodiafiltration; Humans; Hypoglycemic Agents; Metformin; Vasoconstrictor Agents; Vasopressins

Type 2 diabetes and its cardiovascular disease complications are the major public health threats of our century. Although physical activity and dietary changes are the cornerstones in prevention of diabetes, their broad implementation is not elementary and other complementary lifestyle regimens are needed.. Vasopressin (VP) is the main regulator of body water homeostasis, and at insufficient water intake, normal plasma osmolality can be maintained by increased pituitary VP secretion through VP-2 receptor mediated renal water reabsorption. During the last 6 years several independent studies have shown that high circulating VP, measured by the stable VP marker copeptin, predicts development of type 2 diabetes as well as the metabolic syndrome, cardiovascular disease and premature mortality. Interestingly, VP stimulates adrenocorticotrophic hormone, and as a consequence cortisol secretion, through pituitary VP-1B receptors, which could explain why the 25% of the middle-aged population with high circulating VP have a mild Cushing's syndrome-like phenotype. In rats, high VP results in deterioration of glucose tolerance whereas low VP, obtained by high water intake, ameliorates the VP associated dysmetabolic state, suggesting that the relationship between high VP and risk of diabetes and cardiometabolic disease in humans may be causal and reversible by increasing water intake.. With the emerging evidence that high VP, which is present in 25% of the population, is an independent risk factor for diabetes and cardiometabolic disease, VP reduction through water supplementation appears as an attractive candidate intervention to prevent diabetes and its cardiovascular complications.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Drinking; Glycopeptides; Humans; Metabolic Syndrome; Osmolar Concentration; Pituitary Gland, Posterior; Receptors, Vasopressin; Risk Factors; Vasopressins; Water-Electrolyte Balance

We herein present the case of a 53-year-old patient with adrenocorticotropin-independent macronodular adrenocortical hyperplasia (AIMAH), which is a rare form of Cushing syndrome. He had hypercortisolemia and bilateral macronodular adrenal glands with a left side predominance. The administration of vasopressin significantly increased the plasma cortisol level (1.9-fold). Following left adrenalectomy, the patient's hypercortisolemia significantly improved and vasopressin responsiveness was lost, suggesting that the responsiveness originated from the resected left adrenal gland. The marked difference in vasopressin responsiveness between the adrenals corresponded with their asymmetrical size and function. Evaluating the differences in the vasopressin sensitivity may therefore be helpful for understanding the progression of AIMAH.

Topics: Adenoma; Adrenal Cortex; Adrenal Cortex Neoplasms; Adrenalectomy; Adrenocorticotropic Hormone; Cushing Syndrome; Deamino Arginine Vasopressin; Dexamethasone; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Hypertriglyceridemia; Laparoscopy; Male; Middle Aged; Organ Size; Receptors, Vasopressin; Thyrotropin-Releasing Hormone; Vasopressins

Polyuria is a symptom that appears in association with diabetes mellitus. Because sustained polyuria causes serious dehydration, it is believed that the body has a compensating mechanism to alleviate dehydration. In the present study, the role of renal aquaporin 2 (AQP2) in the compensating mechanism was investigated in KKAy mice, a type 2 diabetes model.. The renal AQP2 expression levels in KKAy mice aged between 5 and 24 weeks were determined using Western blotting. The hypothalamic vasopressin mRNA expression levels also were measured by real-time RT-PCR. Insulin was subcutaneously administered to 11-week-old KKAy mice twice a day for 7 days. After insulin treatment, the renal AQP2 protein expression and the hypothalamic vasopressin mRNA expression were measured.. The urinary volumes of 5- and 12-week-old KKAy mice were 1.5 ± 0.3 mL and 9.5 ± 1.2 mL, respectively. The inner medullary AQP2 protein expression of 12-week-old KKAy mice was approximately 2.5-fold higher than that of 5-week-old KKAy mice. The hypothalamic vasopressin mRNA expression of 12-week-old KKAy mice was approximately twice that of 5-week-old KKAy mice. Insulin treatment in KKAy mice resulted in a significant reduction in the plasma glucose level, urinary volume, and inner medullary AQP2 protein and hypothalamic vasopressin mRNA expression.. The present study demonstrated that AQP2 is a renal functional molecule of vasopressin that controls urinary volume and that AQP2 in the kidney increases to alleviate dehydration due to type 2 diabetes with polyuria.

Topics: Animals; Aquaporin 2; Blood Glucose; Blotting, Western; Dehydration; Diabetes Mellitus, Type 2; Disease Models, Animal; Gene Expression Regulation; Hypoglycemic Agents; Insulin; Male; Mice; Polyuria; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vasopressins

Renal resistance to vasopressin has been demonstrated in type 1 diabetes and in type 2 diabetes with nephropathy. However, renal response to vasopressin in type 2 diabetes without nephropathy has not been studied. We studied 10 subjects with poorly controlled type 2 diabetes (PCDS; Hb A(1c) >9%), 10 subjects with well-controlled type 2 diabetes (WCDS; Hb A(1c) <7%), and 10 matched nondiabetic control subjects (NDCS) during a euglycemic 8-h water deprivation test. None of the subjects had nephropathy. Water deprivation caused similar rises in plasma vasopressin concentrations in all three groups, but the rise in urine osmolality in PCDS (280.3 +/- 49.7 to 594.4 +/- 88.5 mosmol/kgH(2)O) was lower than in WCDS (360.7 +/- 142.8 to 794.1 +/- 77.3 mosmol/kgH(2)O, P < 0.001) or NDCS (336.0 +/- 123.3 to 786.5 +/- 63.3 mosmol/kgH(2)O, P = 0.019). Total urine output was higher in the PCDS than in WCDS and NDCS (P < 0.05). Linear regression analysis showed that, in PCDS, the osmotic thresholds for thirst (291.9 +/- 4.6 mosmol/kgH(2)O) and vasopressin release (291.1 +/- 2.9 mosmol/kgH(2)O) were higher compared with WCDS (286.6 +/- 1.8 and 286.0 +/- 3.6 mosmol/kgH(2)O, respectively) and NDCS (286.0 +/- 2.4 and 284.1 +/- 4.7 mosmol/kgH(2)O, respectively) (between groups P < 0.001 for both variables). Under conditions of euglycemia, PCDS have impaired renal response to vasopressin and elevated osmotic threshold for thirst and vasopressin release in response to dehydration. Under conditions of chronic hyperglycemia, these abnormalities may significantly contribute to the development of dehydration in PCDS.

Topics: Aged; Arginine Vasopressin; Diabetes Mellitus, Type 2; Diuresis; Female; Glycated Hemoglobin; Humans; Kidney; Linear Models; Male; Middle Aged; Osmolar Concentration; Sensory Thresholds; Thirst; Urine; Vasopressins; Water Deprivation; Water-Electrolyte Balance

We evaluated how renal vascular reactivity to vasopressin changes when nitric oxide (NO) synthesis varies, as has been reported to occur in the course of insulin-dependent diabetes mellitus. Renal vasoconstrictor responses to vasopressin were obtained in young and older Sprague-Dawley control rats (3 and 10 months old) and in age-matched diabetic rats that had been treated with streptozotocin (60 mg/kg i.v.) at the age of 2 months. In young rats, vasopressin (3-1000 ng/kg/min i.v.) induced in vivo a dose-dependent decrease in renal blood flow, which was diminished in streptozotocin diabetic rats (P<0.05). Similarly, in in vitro perfused kidneys, the concentration-response curve for vasopressin (0.03-10 nM) was shifted 3-fold to the right in kidneys isolated from young diabetic rats (P<0.05). This shift was abolished in the presence of an inhibitor of nitric oxide synthesis, N(G)-nitro-L-arginine (100 microM), in the perfusate. In 10-month-old rats, the in vivo renal vasoconstrictor dose-response curve to vasopressin was shifted 10-fold to the left as compared to that for young rats (P<0.001). This shift was similar in both control and diabetic rats. In conclusion, the present study documented the existence of hyporesponsiveness to vasopressin in the early stage of diabetes, possibly related to nitric oxide overproduction. In contrast, renal vascular hyperreactivity to vasopressin occurs with aging, whether the rats are diabetic or not.

Topics: Aging; Animals; Blood Pressure; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; In Vitro Techniques; Injections, Intravenous; Kidney; Male; Organ Size; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Time Factors; Vasoconstriction; Vasopressins

To test the hypothesis that subnormal thirst sensation could contribute to the development of the hypernatraemia characteristic of hyperosmolar coma, we studied osmoregulation in survivors of hyperosmolar coma.. Eight survivors of hyperosmolar coma, eight control subjects with Type II (non-insulin-dependent) diabetes mellitus and eight healthy control subjects underwent water deprivation during which measurements of thirst, plasma osmolality and vasopressin were taken.. Water deprivation caused greater peak plasma osmolality in the hyperosmolar coma group (301.7 +/- 2.7 mmol/kg) than in Type II diabetic (294.3 +/- 3.2 mmol/kg, p < 0.01) or control group (296.9 +/- 3.0 mmol/kg, p < 0.01) and a greater increase in plasma vasopressin concentration (hyperosmolar coma, 5.8 +/- 1.3 pmol/l, Type II diabetes, 1.8 +/- 1.3 pmol/l, p < 0.001, control subjects, 2.2 +/- 1.8 pmol/l, p < 0.001). Thirst ratings were lower following water deprivation in the hyperosmolar coma group (3.5 +/- 0.8 cm) than in Type II diabetes (7.7 +/- 1.6 cm, p < 0.001) or control subjects (7.4 +/- 1.3 cm, p <0.001), and the hyperosmolar group patients drank less in 30 min following water deprivation (401 +/- 105 ml) than Type II diabetic (856 +/- 218 ml, p < 0.001) or control subjects (789 +/- 213 ml, p < 0.001).. Survivors of hyperosmolar coma have subnormal osmoregulated thirst and fluid intake, which might contribute to the hypernatraemic dehydration typical of the condition.

Topics: Aged; Aged, 80 and over; Arginine Vasopressin; Blood; Dehydration; Diabetes Mellitus, Type 2; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Hypernatremia; Linear Models; Male; Middle Aged; Osmolar Concentration; Thirst; Vasopressins; Water Deprivation; Water-Electrolyte Balance

Vasopressin (VP) hypersecretion is known to occur in diabetes mellitus. Using magnetic resonance (MR) imaging, we evaluated the VP content of the posterior lobe of the pituitary gland in 22 patients with uncontrolled noninsulin-dependent diabetes mellitus. The mean VP level and hemoglobin A1c value were elevated; 6.8 +/- 6.8 pg/mL (normal, 0.3-3.5) and 11.7 +/- 2.1% (normal, < 6%). The signal intensity ratio of the posterior lobe to the pons was calculated on a MR T1-weighted image where the signal intensity reflects VP content and the posterior lobe has a characteristic hyperintense signal under normal conditions. The mean signal intensity ratio (1.34 +/- 0.22) was lower than that in 20 healthy subjects (1.56 +/- 0.13; P < 0.01). In 7 cases, the signal intensity ration was markedly decreased, and the hyperintense signal was absent. The hyperintense signal appeared after diabetic control in all 6 subjects who underwent follow-up MR examinations within 1-2 months. The VP content in the posterior lobe was decreased in patients with uncontrolled diabetes mellitus, which was thought to be caused by persistent VP hypersecretion. The persistent elevation of plasma VP might have some role in the initiation and progression of diabetic complications.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Gland, Posterior; Reference Values; Vasopressins

The present case was a 44-year-old man who had been diagnosed as having noninsulin-dependent diabetes mellitus 2 years before admission. He gradually showed severe neuropathy and emaciation because of poor control of his blood glucose levels. He was admitted to our hospital because of disturbance of consciousness with hyponatremia. The endocrinological findings including thyroid and adrenal functions revealed no abnormalities. Insufficiency of water diuresis was noted in the water loading test. Severe orthostatic hypotension was noted during the standing up test, and an excessive response in the plasma ADH level was also noted. These findings demonstrated that excessive ADH secretion occurred to compensate for the fall in blood pressure because of the breakdown of homeostatic regulation in blood pressure due to diabetic neuropathy. It is suggested that hyponatremia seemed to be subsequently induced by hypersecretion of ADH.

Topics: Adult; Blood Pressure; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Diuresis; Emaciation; Humans; Hyponatremia; Hypotension, Orthostatic; Male; Osmotic Pressure; Saline Solution, Hypertonic; Vasopressins

Evidence that an increase in plasma atrial natriuretic peptide (ANP) concentrations mediates, at least in part, glomerular hyperfiltration in diabetic rats prompted us to study the relationship between ANP and renal haemodynamics in hyperfiltering type 2 diabetic patients in association with other hormones implicated in the control of glomerular filtration rate (GFR) (catecholamines, vasopressin, renin) and in sodium tubular transport (aldosterone, ouabain-displacing factor, ODF). Since hyperglycaemia is also associated to hyperfiltration, diabetic patients who presented with secondary drug failure were studied both in hyperglycaemic and in normoglycaemic condition. For this purpose, 11 normotensive non-macroproteinuric hyperfiltering patients with type 2 diabetes were treated with an 8-day continuous insulin infusion (days 0-7). Dehydration was prevented or corrected and natriuresis was on day 0 above 100 mmol/day. The following parameters were determined on days 0 and 7: GFR and renal plasma flow (RPF) by 99mTc-DTPA and 131I-hippuran clearances; the extracellular volume, assimilated to the DTPA diffusion volume; urinary ODF by receptor-binding assay and urinary as well as plasma catecholamines by HPLC after extraction on alumin. Plasma ANP and antidiuretic hormone (ADH) were measured by radioimmunoassay after extraction on phenyl-silylsilica (ANP) and with ether (ADH). Unextracted plasma was used for radioimmunological measurement of plasma renin activity and aldosterone. When correcting hyperglycaemia to normoglycaemia GFR decreased from high to normal mean value (138 +/- 27 and 115 +/- 6 ml/min, p < 0.001), RPF followed the same trend, and the DTPA diffusion volume did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Atrial Natriuretic Factor; Diabetes Mellitus, Type 2; Female; Glomerular Filtration Rate; Hormones; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Renal Circulation; Vasopressins

Topics: Adenosine Triphosphate; Biological Transport, Active; Diabetes Mellitus, Type 2; Electrophysiology; Galanin; Insulin; Insulin Secretion; Islets of Langerhans; Peptides; Potassium Channels; Somatostatin; Vasopressins

We have characterized a plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and a cytosolic phosphatidylinositol (PI)-specific PLC in human liver. Epinephrine, 1 x 10(-5) M, and vasopressin, 1 x 10(-8) M, stimulated PIP2-PLC which was enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). PI-PLC stimulation was not observed by these agents. Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes. Furthermore, serendipitly we found that PIP2-PLC activity was increased in liver membranes from obese patients with type II diabetes when compared to obese and lean controls. We conclude that in human liver, insulin and IGFs are not members of the family of hormones generating inositol trisphosphate (IP3) as a second messenger. Furthermore, the increased PIP2-PLC in diabetic liver may result in: (a) increased intracellular concentrations of IP3 and thus increased Ca2+, which has been postulated to induce insulin resistance; and (b) increased diacylglycerol and thus increased protein kinase C which phosphorylates the insulin receptor at serine residues inactivating the insulin receptor kinase. While the mechanism of increased PIP2-PLC activity in diabetes is unknown, it may initiate a cascade of events that result in insulin resistance.

Topics: Calcium; Cell Membrane; Cytosol; Diabetes Mellitus, Type 2; Epinephrine; Guanine Nucleotides; Hydrogen-Ion Concentration; Insulin; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Liver; Obesity; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Somatomedins; Time Factors; Type C Phospholipases; Vasopressins