Molecular Basis of Pathogenesis of Diabetes Mellitus Type 2- a New Perspective | Chapter 01 | New Insights into Disease and Pathogen Research Vol. 1
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.
Author(s) Details
Dr. A. S. V. Prasad
Department of Internal
Medicine, G.I.T.A.M Dental Collage, Rishikonda, Visakhapatnam, Andhra Pradesh,
India.
View Volume: https://doi.org/10.9734/bpi/nidpr/v1
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