Int J Mol Sci.: co-auth.: W.Wahli

Int J Mol Sci. 2021 Aug 9;22(16):8555. doi: 10.3390/ijms22168555.

The PPARβ/δ-AMPK Connection in the Treatment of Insulin Resistance

David Aguilar-Recarte 1 2 3Xavier Palomer 1 2 3Walter Wahli 4 5 6Manuel Vázquez-Carrera 1 2 3


The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.

Keywords: AMPK; GDF15; PPARβ/δ; insulin resistance; type 2 diabetes mellitus.