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

and gluconeogenesis (Unger & Orci, 1977). 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 insulin therapy.
Insulin receptor and post-receptor signaling mechanisms are required for
pancreatic β- cell function (Kulkarni, 2002). Current study on insulin receptor
expression in pancreas showed down regulation in diabetic rats. Decrease in
insulin receptor mRNA expression is characteristic of the diabetic state. In
hypoglycemic rats, the insulin receptor expression further down regulated which
showed that insulin levels below and above homeostatic condition affects the
functional regulation of neuronal cells. Strategies have shown that β-cell deletion
of the insulin receptor reduces first-phase insulin release and β-cell insulin content
and causes a progressive deterioration in glucose tolerance (Kulkarni et al., 2002).
Previous studies showed impaired insulin synthesis and marked β-cell failure
during deletion of the insulin receptor gene (Ueki et al., 2006). Recurrent
hypoglycemia causes insulin insensitivity which adversely affects further insulin
signalling in diabetic rats. This contributes to impairment in insulin receptor
synthesis required for insulin signalling in pancreas. The study on the receptor
shows the importance of maintaining euglycemia during diabetes treatment and
the need of avoiding hypoglycemia. Insulin is known to inhibit its own release and
reduce glucagon secretion.
Glucose stimulation of β cells in culture has been shown to result in the
activation of the IR as does the application of exogenous insulin, suggesting that
insulin secreted from β cells binds to its receptor eliciting a physiological response
(O’Neill et al., 2007). Insulin signaling has been shown to be associated with
enhanced proliferation and reduced apoptosis in insulin target tissues (Datta et al.,
1999). Insulin signaling in the pancreas regulates mitochondrial function and has
implications for β cell dysfunction in diabetes (Liu & Chang., 2009). Diabetes in
itself cause β cell dysfunction affecting insulin receptor expression and
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