pituitrin and Diabetes-Mellitus--Type-1

The thymus is the unique lymphoid organ responsible for the generation of a diverse repertoire of T lymphocytes that are competent against non self-antigens while being tolerant to self-antigens. A vast repertoire of neuroendocrine-related genes is transcribed in the nonlymphoid cellular compartment of the thymus (thymic epithelial cells, dendritic cells and macrophages). The precursors encoded by these genes engage two types of interactions with developing T cells (thymocytes). First, they are not processed in a classical neuroendocrine way but as the source of self-antigens that are presented to pre-T cells by the major histocompatibility complex proteins of the thymus. This presentation could be responsible for the establishment of central T-cell self-tolerance to neuroendocrine functions. Second, they also deliver signal ligands that are able to bind to neuroendocrine-type receptors expressed by thymocytes. This interaction activates several types of intracellular signalling pathways implicated in the developmental process of T lymphocytes. Several experimental arguments support a role for thymic dysfunction as a crucial factor in the development of organ-specific autoimmune endocrinopathies, such as 'idiopathic' central diabetes insipidus and type 1 diabetes mellitus. The rational use of tolerogenic neuroendocrine self-antigens for the prevention/treatment of autoimmune endocrinopathies is currently under investigation.

Topics: Animals; Cell Differentiation; Diabetes Insipidus, Neurogenic; Diabetes Mellitus, Type 1; Gene Expression Regulation; Humans; Insulin; Oxytocin; Pituitary Hormones; Self Tolerance; T-Lymphocytes; Thymus Gland; Transcription, Genetic; 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

Advances in genetic engineering will make possible treatment of many pediatric endocrine disorders with replacement therapy. Some of these conditions include short stature, precocious puberty, and diabetes mellitus. Although the availability of such hormonal replacement offers new treatment modalities, an understanding of their mechanism of action and pharmacologic characteristics is crucial to maximize their effectiveness while minimizing possible untoward effects. The clinician must evaluate potential risks and benefits as these substances come to market without definitive answers being available as to their long-term effects.

Topics: Child; Child, Preschool; Diabetes Mellitus, Type 1; Growth Disorders; Growth Hormone; Hormones; Humans; Infant; Insulin; Pituitary Diseases; Pituitary Hormone-Releasing Hormones; Prolactin; Puberty, Precocious; Recombinant Proteins; Somatostatin; Thyrotropin-Releasing Hormone; Vasopressins

Topics: Blood Volume; Child; Craniocerebral Trauma; Deamino Arginine Vasopressin; Dehydration; Diabetes Mellitus, Type 1; Diuresis; Female; Humans; Kinetics; Male; Models, Biological; Neurophysins; Osmolar Concentration; Oxytocin; Pituitary Gland, Posterior; Postoperative Complications; Pregnancy; Pregnancy in Diabetics; Thirst; Urine; Vasopressins

Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors.. DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p = 0.02) and HC (4.8 [4.1-5.5] pmol/l, p = 0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p = 0.01) and higher renin concentration (r: 0.40, p = 0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β ± SE: -6.9 ± 3.4, p = 0.04).. In longstanding type 1 diabetes, copeptin was associated with intrarenal renin-angiotensin-aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.

Topics: Adult; Angiotensin II; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Glycopeptides; Hemodynamics; Humans; Renin; Renin-Angiotensin System; Vascular Resistance; Vasopressins

Topics: Addison Disease; Child; Diabetes Mellitus, Type 1; Humans; Hyponatremia; Male; Natriuresis; Polyendocrinopathies, Autoimmune; Rhabdomyolysis; Vasopressins

The response of arginin-vasopressin (AVP) to baroreceptor activation (tilt testing) was investigated in patients with diabetic autonomic neuropathy (DAN). The present data show that hypothension induced by upright position showed a slight increase of AVP in patients with DAN in comparison with normal subjects and diabetic patients without DAN. These findings suggest that the blunted AVP response to hypothension may be due to lesions of afferent autonomic pathways present in DAN and plays a role in the pathogenesis of postural hypothension.

Topics: Afferent Pathways; Aged; Autonomic Pathways; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Female; Hemodynamics; Humans; Hypotension, Orthostatic; Male; Middle Aged; Saline Solution, Hypertonic; Tilt-Table Test; Vasopressins

Blindness caused by ischemic optic neuropathy in the hospital setting occurs perioperatively and in critically ill patients, but its etiology remains ill defined. We describe four critically ill patients who developed blindness within 1 mo of one another. Three cases occurred outside of the operative arena. Potential risk factors for the development of ischemic optic neuropathy, such as use of vasopressors, venous congestion, and hypotension, are described.

Topics: Accidents, Traffic; Blindness; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diverticulitis; Female; Flail Chest; Hemothorax; Humans; Intensive Care Units; Lung Injury; Male; Middle Aged; Myasthenia Gravis; Myocardial Infarction; Optic Nerve Injuries; Optic Neuropathy, Ischemic; Pancreatitis; Pelvic Bones; Prone Position; Risk Factors; Sepsis; Spinal Fractures; Vasopressins

In rats with streptozotocin-induced diabetes mellitus for 10-20 days, we showed that the abundance of the major medullary transport proteins involved in the urinary concentrating mechanism, urea transporter (UT-A1), aquaporin-2 (AQP2), and the Na+-K+-2Cl- cotransporter (NKCC2/BSC1), is increased, despite the ongoing osmotic diuresis. To test whether vasopressin is necessary for these diabetes mellitus-induced changes in UT-A1, AQP2, or NKCC2/BSC1, we studied Brattleboro rats because they lack vasopressin. Brattleboro rats were given vasopressin (2.4 microg/day via osmotic minipump) for 5 or 12 days. At 5 days, vasopressin increased AQP2 protein abundance but decreased UT-A1 abundance compared with untreated Brattleboro rats. At 12 days, vasopressin increased the abundance of both UT-A1 and AQP2 proteins but did not alter NKCC2/BSC1. Next, untreated Brattleboro rats were made diabetic for 10 days by injecting them with streptozotocin (40 mg/kg). Diabetes mellitus increased the abundance of AQP2 and NKCC2/BSC1 proteins, but UT-A1 protein abundance did not increase. Third, vasopressin-treated Brattleboro rats were made diabetic with streptozotocin for 10 days. In vasopressin-treated Brattleboro rats, diabetes mellitus increased UT-A1, AQP2, and NKCC2/BSC1 protein abundances. Vasopressin significantly increased UT-A1 phosphorylation in vasopressin-treated diabetic Brattleboro rats but not in the other groups of Brattleboro rats. We conclude that 1) administering vasopressin to Brattleboro rats for 12 days, but not for 5 days, increases UT-A1 protein abundance and 2) vasopressin is necessary for the increase in UT-A1 protein in diabetic rats but is not necessary for the increase in AQP2 or NKCC2 proteins.

Topics: Animals; Aquaporin 2; Aquaporin 6; Aquaporins; Diabetes Mellitus, Type 1; Female; Kidney Concentrating Ability; Kidney Medulla; Male; Membrane Transport Proteins; Phosphorylation; Rats; Rats, Brattleboro; Rats, Sprague-Dawley; Renal Agents; Sodium-Potassium-Chloride Symporters; Solute Carrier Family 12, Member 1; Urea Transporters; Vasopressins

The use of desmopressin and vasopressors in cadaveric organ donors is considered a risk factor for graft dysfunction following pancreas transplantation by influencing the microcirculation. The aim of this study was to investigate the influence of these substances on early graft function.. This single-center retrospective trial included 59 patients who underwent simultaneous or solitary pancreas transplantation. The corresponding donor charts were reviewed for the use of vasopressors and desmopressin. Impaired graft function was determined as graft thrombosis or as insulin-dependence for more then 3 days posttransplant. Daily amylase and lipase concentrations from abdominal drains were measured to quantify reperfusion pancreatitis and fistula formation.. Overall, pancreas thrombosis was observed in 4 of 59 (6.8%) recipients. There were no significant differences in thrombosis rate whether the donors received desmopressin (3/38 vs 1/21, P >.1) or the needed vasopressors (3/53 vs 1/9, P >.1). The number of patients who required insulin for more than 3 days posttransplant was comparable whether the donors received desmopressin (9/38 vs 4/21, P >.1), or vasopressors (9/46 vs 3/8, P >.1). At present all recipients with functioning pancreatic grafts (ie, 92.7%) are free of exogenous insulin therapy at 2 to 80 months posttransplant. The amylase/lipase concentrations of peritoneal fluid were independent of the administration of desmopressin or vasopressors in the donors.. In this study donor desmopressin and vasopressor administration did not influence graft function after pancreas transplantation.

Topics: Adult; Cadaver; Cause of Death; Deamino Arginine Vasopressin; Diabetes Mellitus, Type 1; Drainage; Female; Humans; Insulin; Kidney Transplantation; Male; Middle Aged; Organ Preservation; Pancreas Transplantation; Retrospective Studies; Tissue Donors; Treatment Outcome; Vasopressins

1. Synthesis of oxytocin (OT) and arginine-vasopressin (AVP) is increased in induced models of Type I diabetes, such as the streptozotocin model. However, these parameters have not yet been evaluated in spontaneous models, such as the nonobese diabetic mouse (NOD). Therefore, we studied in the magnocellular cells of the paraventricular nucleus (PVN) of nondiabetic and diabetic 16-week-old female NOD mice and control C57B1/6 mice, the immunocytochemistry of OT and AVP peptides and their mRNA expression, using nonisotopic in situ hybridization (ISH). 2. In nondiabetic and diabetic NOD female mice, the number of OT- and AVP-immunoreactive cells were similar to those of the controls, whereas immunoreaction intensity was significantly higher for both peptides in diabetic NOD as compared with nondiabetic NOD and control C57B1/6 mice. 3. ISH analysis showed that the number of OT mRNA-containing cells was in the same range in the three groups, whereas higher number of AVP mRNA expressing cells was found in diabetic NOD mice. However, the intensity of hybridization signal was also higher for both OT and AVP mRNA in the diabetic group as compared with nondiabetic NOD and control mice. 4. Blood chemistry demonstrated that haematrocrit, total plasma proteins, urea, sodium, and potassium were within normal limits in diabetic mice. Thus, NOD mice were neither hypernatremic nor dehydrated. 5. We suggest that upregulation of OT and AVP reflects a high-stress condition in the NOD mice. Diabetes may affect neuropeptide-producing cells of the PVN, with the increased AVP and OT playing a deleterious role on the outcome of the disease.

Topics: Animals; Diabetes Mellitus, Type 1; Female; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Oxytocin; Paraventricular Hypothalamic Nucleus; RNA, Messenger; Specific Pathogen-Free Organisms; Vasopressins

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.

Topics: Adolescent; Adult; Aquaporin 2; Aquaporin 6; Aquaporins; Arginine Vasopressin; Blood Glucose; Creatinine; Diabetes Mellitus, Type 1; Drug Resistance; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Kidney; Kidney Concentrating Ability; Osmolar Concentration; Renal Agents; Urine; Vasopressins

The relationship between erythrocyte sodium lithium countertransport activity (SLC), total exchangeable sodium (NaE), and hormonal control of renal function was examined in 40 normotensive, normoalbuminuric, non-neuropathic Type 1 diabetic subjects, of whom 8 had elevated SLC (> 0.40 mmol Li h-1l-1 rbc). Eleven health controls with normal SLC, who were of comparable age, body mass, and blood pressure were also studied. By contrast with healthy controls, SLC in Type 1 diabetes was not associated with plasma renin activity (PRA), aldosterone, systolic blood pressure or lean body mass. SLC was also unrelated to atrial natriuretic peptide (ANP) (Type 1 diabetes only) and NaE. NaE was not correlated with any other variables. The relationships between PRA and aldosterone in healthy controls were retained in Type 1 diabetes (R2 0.37 supine, p = 0.00001, and 0.27 ambulant, p = 0.0005), as were respective direct and inverse relations between vasopressin and ANP and both PRA (rs 0.54 to 0.57, rs -0.43 to -0.53), and aldosterone (rs 0.78 to 0.80, rs -0.71 to -0.80). Fasting free serum insulin and vasopressin were both inversely related to ANP (rs -0.91 and -0.71, respectively). In the absence of autonomic dysfunction, hypertension or early nephropathy in Type 1 diabetes, increased SLC or exchangeable sodium were unrelated to each other or with hormonal control of sodium balance, but the homeostatic factors controlling hormonal interaction appear to be maintained. The interaction between insulin and hormonal control of sodium and water balance may be modified by circulating free insulin concentrations.

Topics: Adolescent; Adult; Aged; Albuminuria; Aldosterone; Antiporters; Blood Pressure; Body Mass Index; Cholesterol; Creatinine; Diabetes Mellitus, Type 1; Erythrocytes; Glomerular Filtration Rate; Hormones; Humans; Insulin; Middle Aged; Potassium; Reference Values; Renin; Sodium; Triglycerides; Vasopressins

Blood glucose, plasma sodium, bicarbonate (HCO3-), vasopressin, and hematocrit were monitored before and during treatment in patients with uncontrolled insulin-dependent diabetes mellitus (IDDM). These parameters were correlated with simultaneous serial cranial computed tomography readings of brain edema. Six of seven patients had positive computed tomography readings for brain edema on admission. Initial brain edema correlated directly with blood glucose (r = 0.79, P = 0.033) and inversely with HCO3- (r = -0.76, P = 0.047). At 6 h, brain edema still correlated with acidosis (HCO3-; r = -0.79, P = 0.033) but no longer with blood glucose. At that time, however, brain edema correlated with the rate of change in blood glucose (r = 0.915, P = 0.005). Results of interactive stepwise regression analysis suggest that the change in the calculated effective plasma osmolality plays a predominant role in the progression of brain edema during therapy (r = 0.995, P less than 0.001). Thus, although hyperglycemia and acidosis probably predispose to diabetic brain edema, osmotic factors may be major predictors of its evolution. No relationships were detected between brain edema and initiation of insulin therapy, plasma vasopressin, or changes in hematocrit. The factors responsible for initial brain edema and its progression, statistically identified in this study, require reassessment of common theories that attribute brain edema exclusively to therapy.

Topics: Adolescent; Arginine Vasopressin; Bicarbonates; Blood Glucose; Brain; Brain Edema; Child; Diabetes Mellitus, Type 1; Hematocrit; Humans; Osmolar Concentration; Regression Analysis; Sodium; Tomography, X-Ray Computed; Vasopressins

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH), hypothalamic hypogonadism and alopecia universalis occurred in a 31-year-old female with insulin-dependent diabetes mellitus (IDDM). Despite various clinical investigations and careful observation for 20 months, the cause and pathogenesis of SIADH and hypothalamic hypogonadism were not elucidated. The complex of these disorders had not been described. The presence of IDDM and alopecia universalis, in which an autoimmune process has been assumed to be involved, is interesting in considering the pathogenesis of the SIADH and hypothalamic hypogonadism.

Topics: Adrenocorticotropic Hormone; Adult; Alopecia; Clomiphene; Diabetes Mellitus, Type 1; Female; Follicle Stimulating Hormone; Growth Hormone; Humans; Hydrocortisone; Hypogonadism; Inappropriate ADH Syndrome; Insulin; Luteinizing Hormone; Pituitary Gland; Prolactin; Thyroid Hormones; Thyrotropin; Vasopressins

Insulin hypoglycaemia causes a rise in plasma vasopressin concentrations in man and the rat, and vasopressin stimulates glucagon secretion and increases hepatic glucose output in man. Vasopressin has also been suggested to have an important synergistic role with corticotrophin releasing factor in the release of adrenocorticotrophin hormone, and a counter-regulatory role for the hormone has been proposed. As diminished anterior pituitary hormone responses to hypoglycaemia have been reported in diabetes mellitus, we studied the plasma vasopressin responses to insulin-induced hypoglycaemia in 10 patients with established Type 1 diabetes and 10 matched control subjects. Blood glucose fell from 4.5 +/- 0.3 to 1.6 +/- 0.1 mmol l-1 (p less than 0.001) in the diabetic group and from 4.6 +/- 0.2 to 1.5 +/- 0.2 mmol l-1 (p less than 0.001) in control subjects, with delayed blood glucose recovery in the diabetic patients. Plasma vasopressin rose in the diabetic patients from 0.9 +/- 0.2 to 6.9 +/- 2.8 pmol l-1 (p less than 0.001), a significantly greater rise (p less than 0.05) than in the control subjects, 0.8 +/- 0.1 to 2.4 +/- 1.0 pmol l-1 (p less than 0.001). Plasma osmolalities remained unchanged and haemodynamic changes were similar in both groups. There is an exaggerated rise in plasma vasopressin concentrations in diabetic patients in response to insulin-induced hypoglycaemia. The putative mechanisms and potential significance of the exaggerated rise are discussed.

Topics: Adult; Blood Pressure; Diabetes Mellitus, Type 1; Growth Hormone; Hematocrit; Humans; Hydrocortisone; Hypoglycemia; Insulin; Kinetics; Pulse; Reference Values; Vasopressins

Patients with diabetes mellitus have higher levels of coagulation factor VIII than the non-diabetic population. This may be a result of poor metabolic control and could contribute to the development of microvascular complications. During ketoacidosis there are acute changes in plasma concentrations of coagulation factors, some of which may be mediated by the rise in vasopressin that occurs. We have investigated the effects of hyperglycaemia without ketosis on some aspects of haemostasis by manipulating blood glucose concentrations using a Biostator. After a 1h run-in period with the blood glucose at 5 mmol/l, the blood glucose was maintained at 5, 15 and 25 mmol/l and maintained for one hour at each level in six male patients with insulin-dependent diabetes. Insulin was infused at 0.25 mu/kg/min. Venous blood samples were taken at the beginning and end of each hour after the run-in period for assays of factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), ristocetin co-factor (FVIIIR:Co), activated partial thromboplastin time (APTT) and vasopressin (aVP). There was a slight, though statistically insignificant fall in median factor VIII:C concentration at each incremental level of increase in blood glucose. Values (at the beginning and end of each hour) were: 1.0 and 1.1 iu/ml at 5 mmol/l; 0.95 and 0.79 iu/ml at 15 mmol/l; and 0.74 and 0.84 iu/ml at 25 mmol. vWF:Ag and FVIIIR:Co were unchanged. Plasma aVP fell slightly from 1.1 to 0.5 pg/ml. The results indicate that high levels of FVIII seen in diabetes are not due to short-term increases in blood glucose and that acute hyperglycaemia does not promote pro-coagulant changes in blood.

Topics: Adolescent; Adult; Diabetes Mellitus, Type 1; Factor VIII; Humans; Hyperglycemia; Male; Partial Thromboplastin Time; Vasopressins

In rats with streptozotocin-induced diabetes an increase in arterial blood pressure was observed as early as the first week after the drug was injected. Blood pressure reached maximal values around the fourth week and remained stable for a long period of follow-up. The responsiveness of these rats to the three major vasopressor hormones, angiotensin II, norepinephrine, and vasopressin, was decreased in the early phase of diabetes and returned to normal in the late phase. Acute treatment at the third, sixth, and twelfth weeks with blockers of these vasopressor hormones resulted in a significant fall in blood pressure at the third week with captopril and at the twelfth week with propranolol plus phentolamine. No significant fall was observed when a specific vasopressin inhibitor was administered. Good control of the blood pressure was obtained when these rats were treated chronically with captopril or prazosin, and partial control was achieved when they were fed a low salt diet. An attenuation in arterial blood pressure levels was observed in rats with two-kidney, one clip hypertension when diabetes was induced by streptozotocin. Plasma creatine levels in diabetic rats were significantly higher than those in control rats only in the sixth and twelfth weeks. Electron microscopy revealed some minor glomerular lesions only at the twelfth week.

Topics: Angiotensin II; Animals; Blood Pressure; Captopril; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Humans; Hypertension; Hypertension, Renovascular; Kidney; Norepinephrine; Prazosin; Rats; Time Factors; Vasopressins

Body temperature falls during hypoglycaemia, perhaps as a protective mechanism. To test the hypothesis that the skin blood flow response to hypoglycaemia is specifically designed to facilitate heat loss we studied both nutritional blood flow and arteriovenous shunting of blood in skin during prolonged, controlled hypoglycaemia in man. We studied eight otherwise healthy, male, Type 1 (insulin-dependent) diabetic patients. Under Biostator control blood glucose was clamped at 8.0 (7.9-8.9), mmol/l (median and range) for 30 min, reduced to symptomatic hypoglycaemia, 1.7 (1.0-2.6) mmol/l for 20 min then raised to 4.9 (3.3-6.7) mmol/l. Interdigital skin web blood flow (laser doppler flowmeter, nutritional flow) fell during hypoglycaemia from 3.1 (2.2-3.8) to 2.4 (1.2-2.8) volts and remained depressed. In contrast, finger blood flow (venous occlusion plethysmography, arteriovenous shunt flow) started high at 54.7 (17.4-85.6), remained high at 52.7 (38.1-81.4) during hypoglycaemia but fell sharply to 25.3 (4.2-66.2) ml.min-1.100 ml-1 when symptoms were relieved. Plasma adrenaline and vasopressin both rose during hypoglycaemia from 0.4 (0.05-0.8) to 4.5 (2.3-20.2) nmol/l and from 0.5 (0.5-3.5) to 4.4 (2.0-13.9) pg/ml, respectively, and both fell sharply thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Body Temperature; Diabetes Mellitus, Type 1; Epinephrine; Face; Fingers; Forearm; Heart Rate; Humans; Hypoglycemia; Insulin; Insulin, Regular, Pork; Male; Regional Blood Flow; Skin; Vasopressins

Factor VIII (FVIII) and plasminogen activator activity (PAA) rise during hypoglycaemia, and this might contribute to the vascular complications of diabetes. Similar changes in haemostasis accompany raised plasma levels of vasopressin (aVP) and adrenaline. To investigate the effects of these hormones on haemostasis during hypoglycaemia and the role of plasma insulin concentrations, eight insulin-dependent diabetic patients underwent controlled hypoglycaemia for 20 min and 13 diabetic patients were investigated during hyperinsulinaemia with blood glucose maintained at 8.0 mmol/l. During hypoglycaemia, insulin levels increased to median values of 114 mU/l, a VP rose from 0.5 to 4.4 (p less than 0.005) pg/ml and adrenaline from 0.4 to 4.4 nmol/l (p less than 0.005). FVIII coagulant activity (FVIII:C) rose from 0.75 to 1.09 IU/ml (p less than 0.01) and the ristocetin co-factor (FVIIIR:Co) and von Willebrand factor antigen (vWF:Ag) showed similar responses. PAA increased from 156 to 745 units (p less than 0.005). During hyperinsulinaemia, insulin rose following infusion from 24 to 52 and 118 mU/l, maintained for an hour at each level. Despite this, plasma aVP, FVIII:C, FVIIIR:Co, vWF:Ag and PAA remained unchanged. This study indicates that the marked changes in FVIII, vWF and PAA concentrations which accompany hypoglycaemia depend on low blood glucose and not raised plasma insulin. The response in probably mediated by increases in adrenaline and aVP, which are part of the physiological response to hypoglycaemia.

Topics: Adolescent; Adult; Antigens; Diabetes Mellitus, Type 1; Epinephrine; Factor VIII; Hemostasis; Hormones; Humans; Hypoglycemia; Insulin; Male; Middle Aged; Plasminogen Activators; Vasopressins; von Willebrand Factor

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be completely accounted for by recognized stimuli. To determine whether insulin deficiency per se increases plasma vasopressin, we investigated the effect of acute insulin depletion on the osmoregulation of plasma vasopressin in insulin-dependent diabetics. When intravenous insulin infusion was stopped, plasma vasopressin, osmolality, and glucose increased over the ensuing 5 h, whereas plasma sodium decreased, and blood volume and pressure did not change. This increase in vasopressin was not due to a loss of osmoregulation, because changes in plasma osmolality and sodium, induced by infusion of hypertonic saline or water loading, induced appropriate vasopressin responses under insulin deplete as well as replete conditions. However, when plasma osmolality and glucose were raised by infusion of hypertonic dextrose, plasma vasopressin increased significantly in diabetic patients under insulin-deplete but not under insulin-replete conditions and actually decreased in healthy controls. These results indicate that acute insulin depletion increases vasopressin secretion by sensitizing the osmoreceptor to stimulation by hyperglycemia. This change in osmoreceptor specificity may be explained by postulating that glucose transport by osmoreceptor neurons as insulin dependent.

Topics: Adult; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 1; Female; Glucose; Heart Rate; Humans; Insulin; Male; Potassium; Sodium; Urea; Vasopressins; Water-Electrolyte Balance

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be accounted for totally by recognized osmotic or nonosmotic stimuli. To investigate the possibility that regulation of vasopressin secretion is abnormal in this disease, we characterized the vasopressin response to osmotic and hemodynamic stimuli in five uncomplicated, well-controlled insulin-dependent diabetics, and compared the results with those found in nondiabetic volunteers. During osmotic stimulation with hypertonic saline, plasma vasopressin increased in close linear correlation with plasma osmolality or sodium in both groups. However, in the diabetics, the lines describing the relationships between plasma sodium and vasopressin were shifted significantly to the left of normal, suggesting resetting of the osmostat. This shift was not due to abnormal stimulation by hyperglycemia, because increasing plasma glucose and osmolality by intravenous infusion of hypertonic dextrose produced no increase in plasma vasopressin in diabetics or normals. Tilt tests produced a slightly exaggerated increase in plasma vasopressin in diabetics, but their basal and upright pulse rate, blood pressure, plasma renin activity, norepinephrine, and hematocrit were all normal. The results indicate that in diabetic patients the osmoreceptor for osmotic regulation of vasopressin secretion is reset in such a way that higher plasma vasopressin levels are observed at comparable levels of plasma sodium. The exact cause and consequence of this abnormality remain to be determined.

Topics: Blood Pressure; Diabetes Mellitus, Type 1; Hematocrit; Humans; Insulin; Osmolar Concentration; Reference Values; Sodium; Urea; Vasopressins

Topics: Adolescent; Blood Glucose; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Humans; Lipids; Potassium; Sodium; Vasopressins

We report on two children with both Addison's disease and diabetes mellitus, a rare occurrence in children. One of the children first developed Addison's disease and later developed diabetes mellitus, while the other had the onset of diabetes mellitus first and later Addison's disease. In the latter patient a direct relationship was shown between the insulin dose and adrenal cortical hormone. Organ-specific antibody studies are reported and the diagnosis and management of these combined endocrinopathies are discussed.

Topics: Addison Disease; Adrenal Cortex; Adrenocorticotropic Hormone; Autoantibodies; Child; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Organ Specificity; Thyroid Gland; Vasopressins

Three children with diabetes insipidus, diabetes mellitus, optic atrophy, and high-tone deafness were shown to lack vasopressin, indicative of degeneration of the cells of the hypothalamic supraoptic nuclei. The syndrome being due to a single gene defect, inherited as an autosomal recessive, is therefore likely to be the result of an inborn error of metabolism with variable periods of latency in those affected.

Topics: Adolescent; Child; Deafness; Diabetes Insipidus; Diabetes Mellitus, Type 1; Humans; Male; Optic Atrophy; Syndrome; Vasopressins

Topics: Child; Consanguinity; Diabetes Insipidus; Diabetes Mellitus; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Vasopressins

Topics: Adolescent; Chlorpropamide; Diabetes Insipidus; Diabetes Mellitus, Type 1; Genes, Recessive; Humans; Hypertonic Solutions; Male; Optic Atrophy; Osmolar Concentration; Sodium Chloride; Specific Gravity; Urine; Vasopressins

Topics: Adolescent; Adult; Child; Diabetes Insipidus; Diabetes Mellitus, Type 1; Female; Hearing Disorders; Humans; Karyotyping; Male; Optic Atrophy; Vasopressins

Topics: Diabetes Insipidus; Diabetes Mellitus, Type 1; Diagnosis, Differential; Female; Humans; Hypertonic Solutions; Thirst; Vasopressins

Topics: Adult; Animals; Child; Diabetes Insipidus; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Humans; Infant; Male; Middle Aged; Polyuria; Rats; Vasopressins

Topics: Adolescent; Cortisone; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Geriatrics; Gonadal Steroid Hormones; Humans; Hypophysectomy; Insulin; Kidney Diseases; Thyroxine; Vasopressins