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

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Discussion
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. Defects in glucose-triggered 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 for peripheral insulin resistance. In addition to its occurrence in central
nervous system, GABA and GAD have been demonstrated in pancreatic β- cells
(Garry et al,, 1986). Rorsman et al (1989) reported that GABA in pancreas is
comparable to that in the central nervous system, demonstrating the importance of
GABAergic neurotransmission in the pancreas. GABA plays an important role in
the regulation of insulin biosynthesis and functions as an alternative energy source
for the β-cell through GABA shunt.
GABA and its related enzymes have been demonstrated in pancreatic β-
cells of normal rats. GABA induced significant increase in insulin secretion from
pancreas (Adeghate & Ponery, 2002). Our study on pancreatic GABA receptor
expression showed a significant decrease in hypoglycemic rats compared to
diabetic and control rats. GAD expression decreased in hypoglycemic rats,
suggests that hypoglycemia causes decreased GABA synthesis in the pancreas.
This is in accordance with previous study which reported a significant decrease in
GABA in diabetic pancreatic cells (Adeghate & Ponery, 2002) in diabetic
pancreas. Hypoglycemia induced reduction in GABA receptors is suggested to
progressively cause deficit in insulin secretory activity of pancreas thereby
exacerbating the GABA dysfunction induced by diabetes. Thus the results throw
light on maintaining euglycemia during diabetic condition and the avoidance of
hypoglycemic episode during intensive insulin therapy. Gomez et al., (1999)
reported increased plasma insulin mediated by GABA agonists.