Metformin

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Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. See also [https://en.wikipedia.org/wiki/Metformin].
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. See also [https://en.wikipedia.org/wiki/Metformin].
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The molecular mechanism of metformin is not completely understood. Multiple potential mechanisms of action have been proposed: inhibition of the mitochondrial respiratory chain ([[complex I]]), activation of [[AMP-activated protein kinase]] (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of [[protein kinase A]] (PKA), complex IV–mediated inhibition of the GPD2 variant of mitochondrial glycerol-3-phosphate dehydrogenase (thereby reducing glycerol-derived hepatic gluconeogenesis), and an effect on gut microbiota.<ref name="a23">PMID:35238637</ref><ref name="a99">PMID:23835523</ref><ref name="a100">PMID:23840042</ref><ref name="a101">PMID:24847880</ref>
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The molecular mechanism of metformin is not completely understood. Multiple potential mechanisms of action have been proposed: inhibition of the mitochondrial respiratory chain ([[complex I]]), activation of [[AMP-activated protein kinase]] (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of [[protein kinase A]] (PKA), [[complex IV]]–mediated inhibition of the GPD2 variant of mitochondrial glycerol-3-phosphate dehydrogenase (thereby reducing glycerol-derived hepatic [[gluconeogenesis]]), and an effect on gut microbiota.<ref name="a23">PMID:35238637</ref><ref name="a99">PMID:23835523</ref><ref name="a100">PMID:23840042</ref><ref name="a101">PMID:24847880</ref>
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== References ==
== References ==
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Revision as of 12:49, 6 July 2023

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References

  1. ↑ LaMoia TE, Butrico GM, Kalpage HA, Goedeke L, Hubbard BT, Vatner DF, Gaspar RC, Zhang XM, Cline GW, Nakahara K, Woo S, Shimada A, Hüttemann M, Shulman GI. Metformin, phenformin, and galegine inhibit complex IV activity and reduce glycerol-derived gluconeogenesis. Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2122287119. PMID:35238637 doi:10.1073/pnas.2122287119
  2. ↑ Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013 Sep;56(9):1898-906. PMID:23835523 doi:10.1007/s00125-013-2991-0
  3. ↑ Burcelin R. The antidiabetic gutsy role of metformin uncovered? Gut. 2014 May;63(5):706-7. PMID:23840042 doi:10.1136/gutjnl-2013-305370
  4. ↑ Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542-6. PMID:24847880 doi:10.1038/nature13270

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