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

Conclusion
Hypoglycemia is the major problem to blood glucose homeostasis in
treatment of diabetes. The CNS neurotransmitters play an important role in the
regulation of glucose homeostasis. These neurotransmitters mediate rapid
intracellular communications not only within the central nervous system but also
in the peripheral tissues. They exert their function through receptors present in
both neuronal and non-neuronal cell surface that trigger second messenger
signaling pathways. Our findings demonstrated a prominent functional disturbance
in cholinergic and GABAergic system in the hypoglycemic and hyperglycemic
brain which contributes to neuronal damage and reduced behavioural, cognitive
and motor function. Disorders in the transport and metabolism of glucose through
GLUT3 in hypo and hyperglycemia, contributes to neuronal dysfunction and
triggers apoptotic cascade. Bax, apoptotic protein expression, increased in
hypoglycemic rat brain regions and pancreas which demonstrated the central and
peripheral nervous system damage induced by recurrent hypoglycemia during
diabetes treatment. Altered CREB expression shows derangement of CREB
related intracellular signal transduction which closely parallels neuronal
dysfunction. Cholinergic and GABA receptors alteration affected normal
neurotransmission through second messenger enzyme – Phospholipase C and
transcription factor – CREB protein. It was also apparent from the present results
that biochemical alterations produced by hyperglycemia was exacerbated by
recurrent hypoglycemia and adversely affected neurological functions of CNS and
PNS. Higher brain functions cannot adapt to recurrent hypoglycemia which shows
that hypoglycemic condition has more functional damage at the molecular level
than hyperglycemia. It is suggested that the corrective measures for the brain
functional damage caused during diabetes and anti-diabetic treatment, through
cholinergic and GABAergic receptors, have therapeutic role in the management of
hypoglycemia and hyperglycemia.