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

mediated by these receptors and contribute to defective counter regulatory
response to hypoglycemia. In the present study, localization of muscarinic M1,
M3 receptors using confocal laser scanning microscopy showed a decreased mean
pixel value in pancreatic islets of hypoglycemic and diabetic rats. The presence of
ACh in pancreas suggests a physiological role for acetylcholine in pancreatic
function. ACh elicited a significant increase in glucagon secretion in the normal
pancreas. Holst et al (1981) demonstrated that ACh stimulates glucagon secretion
from the isolated canine and porcine pancreases. The response was completely
resistant to hexamethonium and abolished by atropine. This indicates that the
action of ACh on glucagon secretion is via muscarinic receptors. The inability of
ACh to stimulate glucagons release from diabetic pancreas suggests that the
mechanism of action of ACh in diabetes has been impaired. This is in accordance
with our study on muscarinic receptors which showed decreased expression in
diabetic rats.
Our results showed hypofunction of muscarinic receptors in the pancreas
exposed to recurrent hypoglycemia. Havel, (1997) reported that muscarinic
receptors blockade lowered the glucagon response to the insulin-induced
hypoglycemia. Effects of cholinergic mechanisms on glucagon and epinephrine
responses to insulin-induced hypoglycemia showed that glucagon response to
insulin hypoglycemia in normal and short-term diabetic rats increased during
cholinergic receptor activation. Patel (1984) demonstrates that the parasympathetic
nervous system plays an important role in the glucagon release in response to
insulin hypoglycemia in rats. The lack of glucagon response to insulin
hypoglycemia observed in long-term diabetic rats could be due to deteriorated
parasympathetic nervous system and also could be corrected with carbachol, drug
that binds and activates the acetylcholine receptor (Patel, 1984).
Choline increased the acetylcholine content of the pancreas and enhanced
acetylcholine release from minced pancreas, which suggests that choline
stimulates insulin secretion indirectly by enhancing acetylcholine synthesis and
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