The mechanisms of action of metformin

Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, ye...

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Vydáno v:Diabetologia Ročník 60; číslo 9; s. 1577 - 1585
Hlavní autoři: Rena, Graham, Hardie, D. Grahame, Pearson, Ewan R.
Médium: Journal Article
Jazyk:angličtina
Vydáno: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2017
Springer Nature B.V
Témata:
AMP
AMP-activated protein kinase
AMP-Activated Protein Kinases - metabolism
Animals
Antidiabetics
Biguanides - therapeutic use
Blood glucose
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - drug therapy
Diabetes Mellitus, Type 2 - enzymology
Electron transport
Gastrointestinal tract
Glucose
Glucose metabolism
Human Physiology
Humans
Hypoglycemic Agents - therapeutic use
Internal Medicine
Kinases
Liver
Medicine
Medicine & Public Health
Metabolic Diseases
Metformin
Metformin - therapeutic use
Mitochondria
Review
AMPK
Biguanide
Diabetes
Metformin
Review
ISSN:0012-186X, 1432-0428, 1432-0428
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Shrnutí:Metformin is a widely-used drug that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The mechanisms underlying these benefits are complex and still not fully understood. Physiologically, metformin has been shown to reduce hepatic glucose production, yet not all of its effects can be explained by this mechanism and there is increasing evidence of a key role for the gut. At the molecular level the findings vary depending on the doses of metformin used and duration of treatment, with clear differences between acute and chronic administration. Metformin has been shown to act via both AMP-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms; by inhibition of mitochondrial respiration but also perhaps by inhibition of mitochondrial glycerophosphate dehydrogenase, and a mechanism involving the lysosome. In the last 10 years, we have moved from a simple picture, that metformin improves glycaemia by acting on the liver via AMPK activation, to a much more complex picture reflecting its multiple modes of action. More work is required to truly understand how this drug works in its target population: individuals with type 2 diabetes.
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ISSN:0012-186X
1432-0428
1432-0428
DOI:10.1007/s00125-017-4342-z