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

Related Articles

Effect of Lead on Human Blood Antioxidant Enzymes and Glutathione

Human exposure to lead may alter the enzyme antioxidants level and the interaction between antioxidants and blood lead level (BLL) eventually cause oxidative stress. Therefore, the present investigation was carried out t...

Glucose-6-Phosphate Dehydrogenase Deficiency in Individuals Infected with Human Immunodeficiency Virus at the Aminu Kano Teaching Hospital Kano, North Western Nigeria

Background: Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency is the most important disorder of the pentose phosphate pathway in erythrocyte metabolism resulting in decreased activity of the enzyme. In individuals in...

Proximate and Mineral Analysis of Methanolic Leaf Extract of Napoleona imperialis (mkpodu)

Napoleona imperialis is an evergreen non-timber plant that has wound healing and antihypertensive effect. The study was undertaken to evaluate the proximate and elemental analyses of the leaf of Napoleona imperialis. The...

Effect of Enzyme Replacement Therapy on Disease Burden Biomarkers in Gaucher's Disease

Aims: We evaluate the effect of enzyme replacement therapy "ERT" on the plasma levels of some biochemical markers of the disease burden, in pediatric patients with Gaucher's disease "GD", in the form of plasma chitotrios...

Evaluation of Nephroprotective Activity of Aqueous and Hydroethanolic Extracts of Trema guineensis Leaves (Ulmaceae) against Gentamicin-Induced Nephrotoxicity in Rats

Aims: The present study investigated the potential nephroprotective activity of aqueous and hydroethanolic extracts of Trema guineensis leaves (Ulmaceae) and determined the most active extract in rat. Study Design: Trema...

Download PDF file
  • EP ID EP317091
  • DOI 10.9734/IJBCRR/2017/39028
  • Views 114
  • Downloads 0

How To Cite

A. S. V. Prasad (2017). Molecular Mechanism of Metformin in DM2- A New Hypothesis. International Journal of Biochemistry Research & Review, 20(3), 1-13. https://europub.co.uk/articles/-A-317091