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

106
Discussion
Pancreas
Insulin secretion from pancreatic islet β-cells is a tightly regulated
process, under the close control of blood glucose concentrations and several
hormones and neurotransmitters. Insulin secretion from the pancreatic islets are
stimulated by parasympathetic nerves and inhibited by sympathetic nerves (Ahren,
2000). Acetylcholine mediates insulin release through vagal stimulation. ACh is
released from cholinergic synapses on β-cells during the cephalic phase of
digestion causing a transient increase in insulin secretion. Defects in glucosetriggered
insulin secretion are ultimately responsible for the development of type
II diabetes, a condition in which the total β-cell mass is essentially unaltered, but
β-cells become progressively “glucose blind” and unable to meet the enhanced
demand for insulin resulting in peripheral insulin resistance (Rutter, 2001). The
pancreas is innervated by cholinergic fibers (Brunicardi et al., 1995) with ample
amounts of choline acetyltransferase and acetylcholinesterase in islets (Godfrey &
Matschinsky, 1975). Muscarinic M1 and M3 receptors are expressed on islet β -
cells (Iismaa et al., 2000). It is well established that parasympathetic stimulation
of the pancreas potentiates insulin secretion both before and after glucose
absorption from the gut (Strubbe & Steffens, 1993) reinforcing the physiological
importance of this system in 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). 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 reported in long-term diabetic rats could be due to deteriorated