Central Adrenergic Suppression Augments the Insulin and Glucagon Secretory, and the Glycogenolytic Responses in Streptozotocin-Diabetic Rats

Abstract

It has been suggested that the increased activity of the sympathetic nervous system and the resultant increase in the tissue catecholamine levels contribute to the pathogenesis of diabetes. In this study we evaluated the effect of clonidine, a central adrenergic agonist that decreases sympathetic tone, on the serum levels of glucose, insulin, glucagon and norepinephrine and on the hepatic glycogen content in normal and streptozotocin-diabetic rats. The animals were treated with clonidine 25 µg/kg/day interperitoneally for 3 weeks to suppress the central adrenergic impulses. Clonidine treatment significantly increased the weight gain, but did not affect plasma glucose, insulin, glucagon and norepinephrine in the diabetic animals. Pancreatic insulin and liver glycogen contents were significantly higher in the clonidine-treated than in the untreated diabetic rats. However, clonidine did not affect pancreatic insulin and liver glycogen content of nondiabetic animals. The intravenous administration of glucagon increased plasma glucose in the clonidine-treated, but not in the saline-treated diabetic rats. Insulin-induced hypoglycemia significantly enhanced glucagon release in clonidine-treated but not in saline-treated diabetic rats. We conclude that the suppression of central adrenergic activity may ameliorate the effects of insulin insufficiency on pancreatic hormone secretion and hepatic glycogen content.

Adrenergic Blockade in Diabetic and Uninephrectomized Rats: Effects on Renal Size and on Renal and Urinary Contents of Epidermal Growth Factor

“…Tissue and circulating levels of catecholamines, mainly noradrenaline, are increased in poorly metabolically controlled insulin-dependent diabetes mellitus [18, 19, 20, 21]. The activity of the sympathetic nervous system depends on the degree of metabolic control.…”

“…Increased secretion of the catecholamines may be the result of glucopenia in the central nervous system which then, by increased sympathetic tone, elevates plasma glucose and hepatic glucose production [37]. Other investigators have suggested that the increased sympathetic tone in insulin-dependent diabetes mellitus is caused by impaired sensitivity of the hypothalamus to glucose and insulin [18, 38]. …”

“…Diabetic rats have an increased activity of the sympathetic nervous system [18, 19, 20, 21], and, therefore, an adrenergic effect on the renal excretion of EGF is likely in experimental diabetic rats. In order to investigate whether increased tone of the sympathetic nervous system affects the renal excretion of EGF and the diabetes-induced renal growth, experimental diabetic rats were long-term treated with adrenergic antagonists.…”

Effect of Insulin and Clonidine on the Evoked Release of Norepinephrine and Serotonin from the Nucleus tractus solitarius of the Diabetic Rat

“…Enzyme changes associated with monoamine metabolism and neurotransmitter receptors have been pro posed as reasons for these alterations in neu rotransmitter levels and turnover rates [16. 29-32], For example a r and a2-adrenergic receptor densities of central nervous system centers such as amygdala, hypothalamus, and medulla were increased in experimental dia betes, whereas the p-adrenergic receptor den sity was decreased in diabetic mice [ 17], Alterations in regional blood flow have also been a consistent finding in diabetes, pos sibly at the level of the NTS where reflex con trol of blood pressure and many other auto nomic functions are mediated [33][34][35][36][37], Brain stem nuclei are also known to have a relative ly high density of insulin receptor binding sites in specific medullary regions such as the NTS vagal complex and cells of the pontine nuclei [38], Because of previous studies from our laboratory demonstrating that {^-adrener gic mechanisms are altered in diabetes [33], and since the NTS is so closely involved in cardiovascular and respiratory reflex neuro modulation of autonomic function, we chose to examine the stimulated evoked release of [3H]NE and [3H]5-HT from superfused NTS brain slices from both normal and diabetic rats. More specifically, we examined the ef fects of the a?-adrenoceptor antagonist yo himbine and of the agonist clonidine as well as insulin superfusion on the electrically evoked release of [3H]NE and [3H]5-HT.…”