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From early to later stages of Type I Diabetes Mellitus (TIDM), signalling molecules including brain indolamines and protein kinases are altered significantly, and that has been implicated in the Metabolic Disorders (MD) as well as impairment of retinal, renal, neuronal and cardiovascular systems. Considerable attention has been focused to the effects of diabetes on these signalling systems. However, the exact pathophysiological mechanisms of these signals are not completely understood in TIDM, but it is likely that hyperglycemia, acidosis, and insulin resistance play significant roles. Insulin maintains normal glycemic levels and it acts by binding to its receptor, so that it activates the receptor's tyrosine kinase activity, resulting in phosphorylation of several substrates. Those substrates provide binding/interaction sites for signalling molecules, including serine/threonine kinases and indolamines. For more than two decades, our research has been focused on the mechanisms of protein kinases, CaM Kinase and Serotonin transporter mediated alterations of indolamines in TIDM. In this review, we have also discussed how discrete areas of brain respond to insulin or some of the pharmacological agents that triggers or restores these signalling molecules, and it may be useful for the treatment of specific region wise changes/disorders of diabetic brain.

Hyperglycemia and ketoacidosis are the two most serious factors in acute metabolic complications of both type 1 and type 2 diabetes. Dysfunction of the central nervous system is a well-documented complication of diabetes. We and others have previously reported that acute or chronic diabetes in animal's results in altered brain neurotransmitter levels. In this study, we investigated the effects of acute (7 days) glucose-induced hyperglycemia and sodium acetoacetate (NaAcAc) or ammonium chloride (NH4Cl) induced acidosis on the level of indolamines (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)) as well as PKC-alpha expression/activity in discrete areas of rat brain. Glucose-induced (500 mg/kg, bw) hyperglycemic ( approximately 249 mg%) rats showed significant (p

Monoaminergic inputs to the caudal neurosecretory complex (CNc) of Poecilia latipinna have been identified using histofluorescence and immunohistochemical techniques. The present study was undertaken to identify specific monoamines and determine the relative contribution of indolamines and catecholamines in supraspinal and intrinsic innervation of the nucleus. The CNc was deafferented by transecting the spinal cord rostral to the CNc. Ten days subsequently, CNc of spinal-transected and control fish were processed for either biochemical or immunohistochemical analysis. Norepinephrine and serotonin were detected in pooled samples of control CNc. Following deafferentation, the content of both monoamines was diminished. Using immunohistochemical labeling for serotonin or for the catecholamine-synthesizing enzymes, tyrosine hydroxylase (TH) or dopamine-β-hydroxylase (DBH), the number of monoamine fibers was decreased in deafferented CNc compared to control. A substantial serotonergic innervation remains after deafferentation, as evidenced by serotonin-positive neurons and heavy, varicose fibers. Occasional TH/DBH-positive cells and fibers remain after deafferentation. These data suggest that both norepinephrine and serotonin are associated with descending supraspinal projections, while serotonin predominates as the intrinsic monoamine.