NEUROENDOCRINOLOGY
LETTERS
including
Psychoneuroimmunology, Neuropsychopharmacology,
Reproductive Medicine, Chronobiology
and Human Ethology, ISSN 0172–780X
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 (b-adrenergic receptor
antagonist) or yohimbine (a2-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.
CONCLUSION:
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.
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Introduction
Ghrelin
is a newly discovered endogenous ligand for the growth hormone
receptor. Ghrelin can stimulate food intake [1] and growth hormone
release in lower vertebrates [2] as well as in humans [3]. Ghrelin
can stimulate gastric acid secretion [4] as well as adiposity
[5] in mammals. Ghrelin has been shown to be present in the
pancreas and other peripheral tissues [6]. Ghrelin is present
in the arcuate nucleus of the human hypothalamus and pituitary
gland [7]. Moreover, ghrelin has also been demonstrated in the
anterior medial hypothalamus; nucleus magnocellularis preopticus
pars medialis and nucleus chiasmatis of the hypothalamus of
the domestic fowl [8]. This indicates that ghrelin may have
several physiological actions in the peripheral as well as in
the central nervous systems. Since ghrelin has been shown to
stimulate insulin secretion [6] and increase food intake and
body weight [9] acting in part upon hypothalamic neurons regulating
food intake and body composition [10–12] and in part by
interaction at the pituitary [13], we hypothesize that ghrelin
could have an effect on glucagon, a pancreatic hormone involved
in glucose metabolism.
Glucagon-producing
cells are the second largest cell type in the endocrine pancreas.
Moreover, the number of glucagon-producing cells is increased
in experimental diabetes [14]. This increase in the number of
glucagon-producing cells is associated with severe hyperglucagonaemia.
In addition to this, profound weight loss is seen in rats with
streptozotocin-induced diabetes [14].
The purpose of this study was to determine whether ghrelin has
a role in the regulation of glucagon secretion from the pancreas
of diabetic rats. The study also examine the possible mechanisms
by which ghrelin may interact with glucagon in the rat pancreas.
