Muscarinic M1, M3, Nicotinic,GABAA and GABAB Receptor ...

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Discussion
release (Ilcol et al., 2003). Muscarinic M3 receptor appears to be the predominant
subtype expressed by pancreatic β-cells (Gilon & Henquin, 2001). Earlier study
demonstrated that muscarinic stimulation of pancreatic insulin and glucagon
release is mediated by the muscarinic M3 receptor subtype (Duttaroy et al., 2004).
Acute hypoglycemia is associated with stimulation of the pancreatic α-cells and a
concurrent, prolonged suppression of insulin secretion by the β- cells. The islets
receive a rich autonomic innervation and may therefore be subject to control by
adrenergic and cholinergic mechanisms (Roger, 1981). Acetylcholine mediates
insulin release through vagal stimulation. Insulin secretion is stimulated by
parasympathetic nerves and inhibited by sympathetic nerves (Ahren, 2000).
Insulin signaling is important for the regulation of glucagon secretion in both
normoglycemic and hypoglycemic states in vivo (Kawamori et al., 2009).
Glucagon, secreted from the pancreatic α cells, counters the actions of insulin and
corrects hypoglycemia by enhancing hepatic glucose output and gluconeogenesis
(Exton et al., 1966; Maruyama et al., 1984). Inappropriate glucagon secretion is
often observed in patients with diabetes and a defective glucagon response to
hypoglycemia in hyperinsulinemic states frequently exacerbates hypoglycemic
attacks and limits intensive therapy (Amiel et al., 1998). Reduction of the glucose
counter regulatory hormonal responses during prolonged hypoglycemia affecting
the glucagon response and reduced counter regulation to hypoglycemia could
predispose to low plasma glucose concentrations (Guldstrand et al., 2003).
Present study showed the effect of insulin induced hypoglycemia on
pancreatic muscarinic receptors which plays an important role in counter
regulatory mechanisms in response to hypoglycemia. Recurrent hypoglycemia
caused cholinergic hypofunction in pancreas which contributes to defective
counter regulatory response which in turn affects the insulin secretion and
sensitivity of pancreatic cells.