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

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Discussion
exacerbated by recurrent hypoglycemia. Our result is in accordance with early
reports by Biessels et al., (2004) which shows alterations in circulating insulin
levels and insulin signaling pathways due to diabetes and its treatment;
hypoglycemia, directly affecting the brain.
The profound benefits of intensive therapy, such as a decreased
occurrence of neuropathy and microvascular complications reported by the
Diabetes Control and Complications Trial (1993) demonstrate a clear need to
improve long-term glycemic control in insulin-dependent diabetes mellitus.
Unfortunately, this form of therapy results in more frequent episodes of severe
hypoglycemia, which then lead to altered counter regulatory glycemic thresholds
and hypoglycemia unawareness, provoking still more hypoglycemia. In addition,
as the duration of IDDM increases, defects in the counter regulatory pathways
themselves emerge, making hypoglycemia even more likely. In particular, the
release of glucagon, which normally functions as a primary defense against
hypoglycemia (Gerich et al., 1974) is lost in diabetic patients (Santiago et al.,
1980). This plus an impairment in epinephrine release that develops later (Dagogo
et al., 1993) act in concert to limit the diabetic patient's ability to prevent serious
hypoglycemic events that may adversely affect brain function (Ziegler et al.,
1992).
SOD EXPRESSION IN BRAIN AND PANCREAS
Oxidative stress has been suggested as a mechanism contributing to
neuronal death. Early production of reactive species (RS) during the
hypoglycemic episode has been reported. Recent investigations have suggested
that oxidative stress is associated with hypoglycemic neuronal damage (Suh et al.,
2008; Haces et al., 2008, 2010). The deleterious actions of diabetes and its
complication; hypoglycemia, increase oxidative stress in the brain, leading to
increases in neuronal vulnerability. The presence of oxidative stress during
hypoglycemia has been recently suggested (Patocková et al., 2003; Singh et al.,