Metformin improves glycemia independently of skeletal muscle AMPK via enhanced intestinal glucose clearance
Research output: Working paper › Preprint › Research
Metformin is an inexpensive oral anti-hyperglycemic agent used worldwide as a first-choice drug for the prevention of type 2 diabetes mellitus (T2DM). Although current view suggests that metformin exerts its anti-hyperglycemic effect by lowering hepatic glucose production, it has been proposed that metformin also reduce hyperglycemia by increasing glucose uptake in skeletal muscle via activation of AMP-activated protein kinase (AMPK). Herein, we demonstrate in lean and diet-induced obese (DIO) male and female mouse models that the antihyperglycemic effect of metformin occurs independently of muscle AMPK, and instead relies on elevated intestinal glucose clearance. Furthermore, we report that the AMPK activity is elevated in skeletal muscle from patients with T2DM following chronic metformin treatment, but this is not associated with enhanced peripheral insulin sensitivity. These results argue against existing paradigms and emphasize the non-essential role of muscle AMPK but important
role of the intestine for the anti-hyperglycemic effect of metformin.
role of the intestine for the anti-hyperglycemic effect of metformin.
Original language | English |
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Publisher | bioRxiv |
Pages | 1-33 |
Number of pages | 33 |
DOIs | |
Publication status | Published - 24 May 2022 |
- Faculty of Science - Metformin, Anti-hyperglycemic effect, Intestinal glucose clearance
Research areas
Links
- https://www.biorxiv.org/content/10.1101/2022.05.22.492936v1.full.pdf
Submitted manuscript
ID: 328694811