4.7 Review

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

Journal

Publisher

MDPI
DOI: 10.3390/ijms22168555

Keywords

PPAR beta/delta; AMPK; GDF15; insulin resistance; type 2 diabetes mellitus

Funding

  1. Ministerio de Economia y Competitividad of the Spanish Government [RTI2018-093999-B-100]
  2. CIBER de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM)

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Activators of PPAR beta/delta show promise in preventing and treating type 2 diabetes mellitus, mainly through AMPK activation. Further understanding of the mechanisms underlying the effects of the PPAR beta/delta-AMPK pathway may provide a basis for the development of new therapies.
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)beta/delta show promise. Remarkably, most of the antidiabetic effects of PPAR beta/delta agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPAR beta/delta-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 PPAR beta/delta-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.

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