Mechanism of ghrelin-evoked glucagon secretion from the pancreas of diabetic rats.
OBJECTIVE
Ghrelin is a newly discovered peptide, which was first demonstrated in the epithelium of rat stomach. The purpose of the study was to examine the effect of ghrelin on glucagon secretion from pancreatic tissue fragments of normal and diabetic rats.


METHODS
Diabetes was induced by streptozotocin (60 mg Kg body weight 1) given intraperitoneally. Four weeks after the onset of diabetes, pancreatic fragments of normal and diabetic rats were incubated with different concentrations (10 12 10 6 M) of ghrelin. Glucagon release was measured using radioimmunoassay technique.


RESULTS
Ghrelin failed to stimulate or inhibit glucagon secretion from normal rat pancreas. However, it induced significant increases in glucagon secretion from pancreatic tissue fragments of diabetic rats. Either atropine (muscarinic cholinergic receptor antagonist) or propranolol (beta-adrenergic receptor antagonist) or yohimbine (alpha2-adrenergic receptor antagonist) or diltiazem (calcium channel antagonist) did not affect ghrelin-glucagon interaction. Moreover, a combination of atropine, propranolol and yohimbine had no significant effect on the interaction of ghrelin with glucagon.


CONCLUSIONS
The ghrelin-induced glucagon secretion in diabetic rats is not controlled via cholinergic or adrenergic pathways. In conclusion, it appears that the main target of ghrelin in the rat endocrine pancreas is not glucagon-producing cells but rather insulin secreting cells which are more involve in weight gain and body growth.
Adeghate
Ernest
E
Department of Anatomy, Faculty of Medicine and Health Sciences, United Arab Emirates University, PO Box 17666, Al Ain, United Arab Emirates. eadeghate@uaeu.ac.ae
Parvez
Hasan
H
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin; D005934:Glucagon / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism*; D036361:Peptide Hormones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D054439:Ghrelin; D018727:Muscarinic Antagonists; D036361:Peptide Hormones; D005934:Glucagon