Molecular Mechanism of Metformin in DM2- A New Hypothesis | Chapter 07 | Current Trends in Medicine and Medical Research Vol. 1
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.
Biography of author(s)
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/ctmmr/v1
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