Molecular Basis of Pathogenesis of Diabetes Mellitus Type 2- a New Perspective
Decreased insulin secretion due to beta cell dysfunction of the pancreas and defective utilization of insulin due to insulin resistance / Hyperinsulinemia are two important issues in the pathogenesis of DM2. There are many explanations in the literature to account for these two observed phenomena and their interrelationship. DM2 is believed to occur due to a complex interplay of environmental and Behavioural factors in genetically predisposed persons. Among the theories explaining the pathogenesis of DM2, the viscera- Portal hypothesis, the Ectopic fat hypothesis and the adipose tissue as an endocrinal gland are prominent. Besides, the role played by oxidative stress, metabolic stress, mitochondrial dysfunction, endoplasmic reticulum stress, etc. are also advanced. It is felt that basic to and at the core of all the observed facts, is the shift of energy metabolism from normal glycolysis to B- oxidation of fats. Hence, how B – oxidation prevails over glycolysis is the fundamental issue to be addressed together with its interrelationships with insulin resistance, as to which is the cause and which is the effect. At the molecular level, an attempt to find answers to the above questions is made in this paper.
To this extent, the Randle fatty acid cycle (Substrate competition theory of Randle) is suitably modified and applied to explain the switch of Energy metabolisms in DM2. Defective disulfide bond formation of the insulin receptor which makes it physiologically ineffective, is suggested as the cause of the insulin resistance where as the prevailing molecular mechanisms stress on post-receptor signaling defect. The cause and effect of both are discussed. This line is considered to be a departure from traditional approaches broached above and briefly outlined in this article.
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A. S. V. Prasad
Department of Internal Medicine, G.I.T.A.M Dental Collage, Rishikonda, Visakhapatnam, Andhra Pradesh, India.
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Beta cell dysfunction Book hyperinsulinemia Insulin resistance randle cycle and disulfide bonds Science