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

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

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signals (Zawalich & Rasmussen, 1990). While the preeminent nutrient fuel that<br />

regulates secretion is glucose, it is also clear that the vagally derived signal<br />

acetylcholine plays an important role (Shiota et al., 2002). The underlying<br />

explanation for impaired insulin secretion in diabetes resides, in the inability of<br />

glucose to activate information flow in the phospholipase C/protein kinase C<br />

(PLC/PKC) signal transduction system to the same quantitative extent in mouse<br />

islets as it does in rat <strong>and</strong>, presumably, human islets as well. Our study showed a<br />

decreased expression of phospholipase C expression in the pancreatic islets of<br />

hypoglycemia <strong>and</strong> diabetic rats which shows that hypoglycemia <strong>and</strong> the<br />

subsequent glucose deprivation adversely affects the pancreatic second messenger<br />

enzyme regulation. The impact of acetylcholine on the β cell is initiated by the<br />

interaction of the neurotransmitter with the muscarinic cholinergic receptor, the<br />

activation of phospholipase C <strong>and</strong> the subsequent generation of inositol<br />

phosphates <strong>and</strong> diacylglycerol (Berridge, 1987; Gilon &. Henquin, 2001). The<br />

decreased phospholipase C expression is associated with impaired cholinergic <strong>and</strong><br />

GABAergic eceptor signaling during hypoglycemia <strong>and</strong> hyperglycemia.<br />

Cholinergic stimulation of the β cell activates the insulin secretory<br />

process, a response that is mediated by PLC (Kelley et al., 1995). The nature of<br />

the receptor type that couples the activation of PLC to release has yet to be<br />

precisely determined <strong>and</strong> both the muscarinic <strong>M1</strong> <strong>and</strong> <strong>M3</strong> receptor types appear to<br />

be expressed in the β cell (Lismaa et al., 2000). Our study on PLC expression<br />

shows that glucose deprivation is detrimental to innate insulin secreting function<br />

<strong>and</strong> other functions associated with pancreas. Thus, hypoglycemia exacerbates the<br />

dysfunction caused by diabetes.<br />

CREB PROTEIN EXPRESSION IN BRAIN OF EXPERIMENTAL RATS<br />

The cAMP responsive element binding protein (CREB) is a nuclear<br />

protein that modulates the transcription of genes with cAMP responsive elements<br />

in their promoters. CREB is a basally expressed, post-translationally activated<br />

143

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