Metformin improves glycemia independently of skeletal muscle AMPK via enhanced intestinal glucose clearance

Rasmus Kjøbsted*, Jonas Møller Kristensen, Jesper Bratz Birk, Nicolas Oldenburg Jørgensen, Kohei Kido, Nicoline Resen Andersen, Jeppe K Larsen, Marc Foretz, Benoit Viollet, Flemming Nielsen, Kim Brøsen, Niels Jessen, Ylva Hellsten, Kurt Højlund, Jørgen Wojtaszewski

*Corresponding author af dette arbejde

Publikation: Working paperPreprint

Abstract

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.
OriginalsprogEngelsk
UdgiverbioRxiv
Sider1-33
Antal sider33
DOI
StatusUdgivet - 24 maj 2022

Bibliografisk note

(Preprint)

Emneord

  • Det Natur- og Biovidenskabelige Fakultet

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