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Role of oxytocin in glucose homeostasis and weight gain
The overall aim of this thesis was to study metabolic functions of oxytocin in particular in relation to glucose, insulin and glucagon.
Application of oxytocin locally in the pancreas (microdialysis technique) increased insulin (RIA) and glucagon (RIA) release. Furthermore, specific binding-sites for oxytocin were demonstrated on the glucagon producing cc-cells (autoradiography). Oxytocin administered intracerebroventricularly (i.c.v., 2ng) increased plasma levels of insulin but not of glucagon.
The effect on insulin was blocked by atropine. These data show that oxytocin may increase glucagon and insulin secretion by a local mechanism possibly linked to activation of cholinergic neurons in the dorsal motor nucleus of the vagal nerv (DMX). In support of a physiological role for oxytocin in glucose homeostasis, the increase of glucagon and glucose caused by suckling in lactating rats was blocked by a specific oxytocin receptor antagonist l-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin (Img/kg, s.c. Ferring, Malmö, Sweden). In addition, blood glucose levels were decreased in nonlactating female rats after injections (i.p) of the antagonist . Furthermore, 24 h of starvation in lactating rats, as well as insulin-induced hypoglycemia in male and in nonlactating female rats caused an increase in plasma levels of oxytocin.
I.c.v. administration of oxytocin (2 ng) lowered CCK (RIA) and somatostatin (RIA) levels, an effect that was blocked by atropine pretreatment, indicating that vagal cholinergic fibers are involved.
Oxytocin administered i.c.v. (5 µg) increased daily weight gain and food intake in female rats from a Sprague Dawley substrain, characterized by low spontaneus weight gain. The weight gain may not only be due to the increased food intake but also to an increased anabolic metabolism e.g. induced by the changed pattern of pancreatic and gastrointestinal hormones.
The 5-HT1A receptor agonist 8-OH-DPAT (0.5 mg/kg s.c.) increased insulin and decreased CCK and somatostatin secretion. These effects were abolished by pretreatment with the oxytocin antagonist. The 8-OH-DPAT-induced effects on insulin, CCK and somatostatin could be mediated by a 5-HT1A receptor mediated activation of oxytocinergic fibers projecting from the paraventricular nucleus in the hypothalamus to the DMX and consequent activation of vagal cholinergic neurons.
Oxytocin (HPLC and RIA) as well as mRNA for oxytocin (solution hybridization technique) were demonstrated in pancreatic tissue. This suggests that oxytocin may by produced in the pancreas. Streptozotocin treatment did not affect pancreatic content of oxytocin or oxytocin mRNA which indicates that B-cells are not the source of pancreatic oxytocin. The localization as well as the role of pancreatic oxytocin remains to be established.
History
Defence date
1995-11-23Department
- Department of Physiology and Pharmacology
Publication year
1995Thesis type
- Doctoral thesis
ISBN-10
91-628-1813-9Language
- eng