International Journal of Biochemistry Research & Review, ISSN: 2231-086X,Vol.: 20, Issue.: 3
Molecular Mechanism of Metformin in DM2- A New Hypothesis
A. S. V. Prasad1* 1Department of Internal Medicine, G.I.T.A.M Dental Collage, Rishikonda, Visakhapatnam, Andhra Pradesh, India.
A. S. V. Prasad1*
1Department of Internal Medicine, G.I.T.A.M Dental Collage, Rishikonda, Visakhapatnam, Andhra Pradesh, India.
(1) Halit Demir, Professor, Department of Chemistry, Faculty of Art and Science Yuzuncu, Yil University, Turkey.
(1) Arthur Chuemere, University of Port Harcourt, Nigeria.
(2) Dhastagir Sheriff, Benghazi University, North Africa.
(3) César Luiz Da Silva Guimarães, Brazilian Institute of Environment and Natural Renewable Resources, Brazil.
Complete Peer review History: http://www.sciencedomain.org/review-history/23051
Metformin, the antihyperglycaemic drug, though in use since 1957 eluded as to its mechanism of action till date. There is some truth but not the whole truth, in even the much-favoured mechanisms of AMP-stimulated protein kinase (AMPK) stimulation and inhibition of complex 1 of Electron Transport Chain (ETC), as there are objections, unresolved, as yet. Subsequent innovative mechanisms, like gut- mediated responses-involving glucagon-like peptide (GLP 1) and sodium-glucose transporter protein (SGLT 1) or signalling pathways involving transcription factors like a mammalian target of repamycine (mTOR C2), sirtuin 1 (SIRT 1) etc., and the recently proposed brain-gut- liver axis fared no better. The obvious truth to be accepted is that probably no single mechanism can explain all the observed phenomena. An attempt is made to rope in all mechanisms into one, invoking the glucagon signalling pathway, by a non-AMPK, non-Complex1 inhibitory mechanism by the proposed hypothesis. To this extent, new concepts like gate control concept and Warburg- like effect in diabetes mellitus type2 (DM2) are proposed. It is conceptualised that deranged glycolysis is at the root cause of the disturbed energy metabolism in DM 2 and the answer to restore the same lies in a reversal of the factors that lead to derailed glycolysis. Besides, a brief recapitulation of what is known is attempted, with emphasis on the bottlenecks of each of these mechanisms.
AMPK (AMP-stimulated kinase); ETC (Electron Transport Chain); glucagon signalling pathway; GLP 1 (Glucagon-like polypeptide 1); C AMP (Cyclic amp).
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