Metformin a well known agent having multiple uses including the diabetes as a major use various effects has been mentioned in various books but the scientific justification is lacking can any body explain in details?
1.Sensitization of insulin receptors
2.Decreasing glucagon levels
3. Increasing conversion of glucose into lactic acid
4. Increasing glycolysis etc
See these two papers:
Article Metformin Inhibits Gluconeogenesis by a Redox-Dependent Mech...
Article Metformin suppresses gluconeogenesis by inhibiting mitochond...
-Brandon
You can benefit from the following links.
1. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clinical Science (London, England : 1979). 2012;122(6):253-270. doi:10.1042/CS20110386.
2. C Ortega-González, L Cardoza, B Coutiño, R Hidalgo, G Arteaga-Troncoso and A Parra .Insulin sensitizing drugs increase the endogenous dopaminergic tone in obese insulin-resistant women with polycystic ovary syndrome . Journal of Endocrinology (2005) 184, 233–239
3. Shweta Sharma, Hemant Singh, Nabeel Ahmad, Priyanka Mishra, Archana Tiwari. The role of melatonin in diabetes: therapeutic implications. Arch Endocrinol Metab. 2015;59/5.
4. Graham Rena & Ewan R. Pearson & Kei Sakamoto .Molecular mechanism of action of metformin: old or new insights? Diabetologia (2013) 56:1898–1906
5. L. Nesti,A. Natali .Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data. 201727( 8), 657–669
6. Andrew James Mulherin.Mechanisms underlying metformin-induced secretion of glucagon-like peptide-1 from the intestinal L-cell . University of Toronto, 2011
7. Dumitrescu et al.Metformin-Clinical Pharmacology in PCOs. Journal of Medicine and Life Vol. 8, Issue 2, April-June 2015, pp.187-192
Dear Ashique Ali
Good day. Generally you have explained the mechanism by your self. Rest have been explained by others. I will add to this discussion is a simple slide with a reference from a tutorial. It will simply the whole mode of insulin and metformin effect in reducing glucose in the body.
Check out the attachment. It simplifies.
However, with the emergence of genomics very detailed signaling networks for metformin have been elucidated along with genes and the down stream pathways have been discovered but i guess the diagram over simplifies the understanding and hopefully clarifies the question to some extent.
Reference for detailed genomic level understanding is as below:
Article Deciphering Signaling Pathway Networks to Understand the Mol...
Warm regards
Dr Sikandar
Interesting... While metformin facilitates GLUT-4 translocation via AMPk pathway, does metformin actually reduces glucagon levels too, Dr.Ashique Ali?!
Dear Venugopal
Good day. You definitely have a point here. While the effects of metformin on reducing insulin resistance, decreasing hepatic gluconeogneisis and cellular level effects in the shape of increase uptake thru GLUT-4 translocation and by stimulating AMPK (the energy sensor)., glucoagon is also inhibited by metformin and may be an important one.
Article Metformin-Mode of action and clinical implications for diabe...
So this all seem quite contrasting and difficult to interpret . But as for as type-2 diabetes is concerned, the relationship between insulin (decreasing glucose in blood) and glucagon (increasing glucose in blood) seems altered. Probably due to insulin resistance the insulin secretion remains high but least effective while the glucagon still seems to pushing more glucose into blood. So metformin tries to reverse the situation to normal by also affecting glucagon.
So this is my interpretation and of the insulin-glucagon contrast happening in type-2 diabetes due to insulin resistance and the way metformin attempts to bring it back to normal.
Regards
Dr Sikandar
Dear Dr.Sikandar,
Thats awesome.
Thank you for your reply. The fine balance required between insulin and glucagon is very much getting established of late, and it is really interesting to know that metformin ticks all the boxes of T2DM, very much smilar to GLP-1 analogs.
Thank you for sharing the article too.
Many thanks,
Dr Venugopal V
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