pituitrin and Insulin-Resistance

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

Topics: Animals; Diagnosis, Differential; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Membrane Proteins; Mutation; Prognosis; Sarcoplasmic Reticulum; Stress, Physiological; Vasopressins; Wolfram Syndrome

Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia. This review analyses the relationship of cortisol excess, both locally and at tissue level, to these cardiovascular risk factors, and to putative mechanisms for hypertension. Previous studies have examined correlations between cortisol, blood pressure, and other parameters in the general population and in Cushing's syndrome. This review also details changes induced by short-term cortisol administration in normotensive healthy men.

Topics: Blood Pressure; Cardiac Output; Cardiovascular Diseases; Cushing Syndrome; Female; Humans; Hydrocortisone; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin Resistance; Male; Obesity; Plasma Volume; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System; Vascular Resistance; Vasodilation; Vasopressins

Topics: Adrenocorticotropic Hormone; Diabetes Mellitus; Dose-Response Relationship, Drug; Drug Resistance; Endocrine System Diseases; Gonadotropins; Hormones; Humans; Insulin Resistance; Neuromuscular Diseases; Obesity; Parathyroid Hormone; Receptor, Insulin; Receptors, Cell Surface; Syndrome; Thyrotropin; Vasopressins

The clinical features, genetics, pathophysiology, and management of endocrine diseases in which primary hormone resistance is the fundamental defect have been reviewed. Primary hormone resistance has been documented for nearly all hormones--vasopressin, parathyroid hormone, growth hormone, adrenocroticotropin, thyrotropin, gonadotropins, insulin, androgens, cortisol, aldosterone, progesterone, thyroid hormones, and vitamin D. A striking exception is estradiol, a steroid that may be vital for early embryonic development. Most of the hormone unresponsiveness syndromes represent only partial defects, and it is likely that most such patients go unrecognized. Therefore, hormone resistance should be suspected not only when a patient presents with hypofunction of particular endocrine system combined with high endogenous hormone levels but also whenever apparently normal function of an endocrine system is associated with inappropriately elevated levels of the corresponding hormone. The value of these defects in hormone responsiveness as a natural laboratory for the study of the normal mechanisms of hormone action is discussed.

Topics: Adrenocorticotropic Hormone; Diabetes Insipidus; Endocrine System Diseases; Gonadal Steroid Hormones; Growth Hormone; Hormones; Humans; Insulin; Insulin Resistance; Parathyroid Hormone; Thyrotropin; Vasopressins

Reciprocal interactions closely connect energy metabolism with circadian rhythmicity. Altered clockwork and circadian desynchronization are often linked with impaired energy regulation. Conversely, metabolic disturbances have been associated with altered autonomic and hormonal rhythms. The effects of high-energy (HE) diet on the master clock in the suprachiasmatic nuclei (SCN) remain unclear.This question was addressed in the Sand rat (Psammomys obesus), a non-insulin-dependent diabetes mellitus (NIDDM) animal model. The aim of this work was to determine whether enriched diet in Psammomys affects locomotor activity rhythm, as well as daily oscillations in the master clock of the SCN and in an extra-SCN brain oscillator, the piriform cortex. Sand rats were fed during 3 months with either low or HE diet. Vasoactive intestinal peptide (VIP), vasopressin (AVP) and CLOCK protein cycling were studied by immunohistochemistry and running wheel protocol was used for behavioral analysis. High energy feeding dietary triggered hyperinsulinemia, impaired insulin/glucose ratio and disruption in pancreatic hormonal rhythms. Circadian disturbances in hyper-insulinemic animals include a lengthened rest/activity rhythm in constant darkness, as well as disappearance of daily rhythmicity of VIP, AVP and the circadian transcription factor CLOCK within the suprachiasmatic clock. In addition, daily rhythmicity of VIP and CLOCK was abolished by HE diet in a secondary brain oscillator, the piriform cortex. Our findings highlight a major impact of diabetogenic diet on central and peripheral rhythmicity. The Psammomys model will be instrumental to better understand the functional links between circadian clocks, glucose intolerance and insulin resistance state.

Topics: Animals; Biological Clocks; Body Weight; Brain; CLOCK Proteins; Diet; Dietary Fats; Dietary Fiber; Eating; Gene Expression Regulation; Gerbillinae; Insulin Resistance; Somatostatin; Vasoactive Intestinal Peptide; 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

Nesfatin-1, derived from nucleobindin-2 (NUCB2), is expressed in the hypothalamus, including the paraventricular nucleus (PVN), an integrative center for energy homeostasis. However, precise role of the NUCB2/nesfatin-1 in PVN remains less defined. The present study aimed to clarify physiological and/or pathophysiological roles of endogenous NUCB2/nesfatin-1 in PVN by using adeno-associated virus vectors encoding short hairpin RNAs targeting NUCB2 in mice. PVN-specific NUCB2 knockdown primarily increased food intake and decreased plasma oxytocin level specifically in light phase, leading to increased body weight gain without affecting energy expenditure. Furthermore, high-salt diet increased the systolic blood pressure, plasma arginine vasopressin (AVP) and AVP mRNA expression in PVN, and all these changes were blunted by PVN-specific NUCB2 knockdown. These results reveal that the endogenous NUCB2/nesfatin-1 in PVN regulates PVN AVP and oxytocin and consequently the fluid and energy balance.

Topics: Adiposity; Animals; Blotting, Western; Calcium-Binding Proteins; Calorimetry; DNA-Binding Proteins; Feeding Behavior; Immunohistochemistry; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Neurons; Nucleobindins; Oxytocin; Paraventricular Hypothalamic Nucleus; RNA, Small Interfering; Vasopressins

The discovery of apelin, an endogenous ligand of the orphan APJ receptor, constitutes an important advance in both fundamental research and clinical medicine. Experimental data have shown that apelin has a diuretic effect via its central and renal actions: by inhibiting the phasic activity of vasopressinergic neurons and systemic secretion of vasopressin and its direct effect on the renal microcirculation and probably tubular function. Besides its diuretic action, when injected into the blood stream, apelin decreases blood pressure and increases the contractile force of the myocardium while decreasing pre- and post-load, actions opposing those of vasopressin and angiotensin II. Taken together, these data show that this new circulating vasoactive (neuro)peptide could play a crucial role in maintaining water and electrolyte balance and cardiovascular functions. Finally, a systemic injection of apelin in insulin-resistant mice decreases glycemia and enhances glucose uptake in skeletal muscle and adipose tissue, contributing to homeostatic control of blood glucose. Clinically, the development of non-peptide analogs of the apelin receptor could provide new therapeutic tools potentially useful for the treatment of heart failure, states of water and/or electrolyte retention, and type 2 diabetes mellitus.

Topics: Adipose Tissue; Amino Acid Sequence; Angiotensin II; Animals; Apelin; Blood Glucose; Blood Pressure; Cattle; Diuresis; Diuretics; Heart; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Kidney; Male; Mice; Molecular Sequence Data; Muscle, Skeletal; Rats; Vasopressins; Water-Electrolyte Balance

The hormonal control of glycogen synthase and phosphorylase interconversion was investigated in hepatocytes isolated from lean and genetically obese (fa/fa) rats. In cells from obese animals, the inactivation of synthase by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), phospholipase C, vasopressin and the alpha 1-adrenergic agonist phenylephrine was markedly impaired, and the property of PMA to counteract phosphorylase activation by phenylephrine was attenuated. The maximal response of phosphorylase activation to phenylephrine and vasopressin was increased in obese-rat hepatocytes, but the sensitivity to these hormones was similar to that in lean-rat hepatocytes. These observations indicate that the defect in protein kinase C that we reported previously in heart of insulin-resistant fa/fa rats [van de Werve, Zaninetti, Lang, Vallotton & Jeanrenaud (1987) Diabetes 36, 310-319] is probably also expressed in liver.

Topics: Animals; Enzyme Activation; Female; Glycogen Synthase; Insulin Resistance; Liver Glycogen; Obesity; Phenylephrine; Phorbol Esters; Phosphorylases; Protein Kinase C; Rats; Stimulation, Chemical; Type C Phospholipases; Vasopressins