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

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Discussion
The ability to sense a reduction in blood glucose levels and the counter
regulatory mechanisms responsible of its correction are impaired in patients with
type 1 diabetes, which make them susceptible of suffering from hypoglycemia
(Becker & Ryan, 2000; Jones & Davis, 2003; Cryer, 2006). Antecedent
hypoglycemia is a primary factor in the development of hypoglycemia-associated
autonomic failure, a pathophysiological condition in diabetic patients that is
characterized by diminished hypoglycemic awareness and impaired glucose
counter regulation. During diabetes there is decrease in body weight as a result of
altered metabolic function. There was a significant decrease in the circulating
insulin level of diabetic rats when compared to control group.
Administration of 1.5 U/kg of regular insulin produced a fall in glucose
level below 50mg/dL after 1 hour in C + IIH rats. The minimum required dose to
produce irreversible severe hypoglycemia was 0.5 U/kg (Abdul-Ghani et al.,
1989). In D + IIH rats, administration of 10 U/kg of insulin decreased the blood
glucose level below 50mg/dL after 3 hours. Fluctuations in blood glucose are
known to induce changes in neuronal function and therefore be used as a tool to
investigate cognitive functioning (Deary., 1993). It is well recognized that the
glucose level is the primary determinant of the hormonal and metabolic counter
regulatory responses to insulin induced hypoglycemia. A single episode of very
mild hypoglycemia (56 mg/dL) causes a reduction of neuroendocrine counter
regulation that is readily discernible about 24 h later. A similar effect of a single
hypoglycemic episode has been shown in healthy (Hvidberg et al., 1996) and
diabetic (Dagogo et al., 1993) humans. The glycemic levels during antecedent
hypoglycemia in those studies were (46–50 mg/dL). The hypoglycemic counter
regulatory mechanisms are blunted irreversibly by disease duration or by acute
episodes of prior stress (Ertl & Davis., 2004).
Recurrent episodes of hypoglycemia have been demonstrated to reduce
subsequent endocrine counter regulation (Davis & Shamoon, 1991; Heller &
Cryer, 1991; Widom & Simonson, 1992; Veneman et al., 1993; George et al.,