Molecular Mechanism of Metformin in DM2- A New Hypothesis
Journal Title: International Journal of Biochemistry Research & Review - Year 2017, Vol 20, Issue 3
Abstract
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.
Authors and Affiliations
A. S. V. Prasad
Keywords
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- EP ID EP317091
- DOI 10.9734/IJBCRR/2017/39028
- Views 106
- Downloads 0
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