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

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Discussion
glycemic control is also associated with an increased incidence of therapy-induced
hypoglycemic events (Cryer, 1994). The pancreatic islets are richly innervated by
parasympathetic, sympathetic and sensory nerves. Neurotransmitters are stored
within the terminals of these nerves, both acetylcholine and noradrenalin and
several neuropeptides. ACh has been shown to be present in normal and diabetic
pancreas (Luiten et al., 1986). Expression of muscarinic receptors in rat islets was
established by reverse transcriptase-polymerase chain reaction and quantified by
RNase protection. Both methods indicated that muscarinic M1 and M3 receptors
were expressed approximately equally in the various cellular preparations (Lismaa
et al., 2000) which signify the importance of muscarinic receptors in maintaining
glucose homeostasis. During hypoglycemia, low circulating levels of glucose are
detected by central and/or peripheral glucoreceptors. This information is relayed
via central autonomic circuits that quickly correct this potentially dangerous
condition causing the release of glucogenic hormones – glucagon from the α-cells
of the pancreas and adrenaline from the adrenal medulla and inhibition of insulin
secretion (Yamaguchi, 1992; Havel & Taborsky, 1994). Neuroglucopenia
stimulates the secretion of counter-regulatory hormones, among which exists
glucagon secretion by the pancreatic β-cells through activation of autonomic
neurons (Flechtner et al., 2006). Cholinergic input to the islets plays a particularly
important role in the regulation of circulating insulin levels (Walter et al., 2004).
The ability of α cell to respond appropriately to hypoglycemia and to
arginine during hyperglycemia is dependent on normal β-cells function
(McCulloch et al., 1989). Present study on pancreatic muscarinic receptor binding
and gene expression along with immunocytochemistry revealed a significant
decreased expression of muscarinic receptors. During hypoglycemic condition,
total muscarinic, muscarinic M1 and M3 receptor binding parameters decreased
when compared to diabetic and control. Gene expression studies also showed the
down regulation of muscarinic M1, M3 receptors in hypoglycemic rats compared
to diabetic rats. These muscarinic receptor alterations impair the functions