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

Abstract

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.

Grape seed extract supplementation modulates hepatic lipid metabolism in rats. Implication of PPARβ/δ

“…Thus, the effects in AMPK and PPARβ/δ activation levels elicit by GSE might be derived by generation of endogenous PPARβ/δ ligands in the liver that might protect against IR, type 2 diabetes mellitus, and its associated disorders. 74 Nevertheless, additional metabolic studies are required in liver and other tissues affected by PPARβ/δ activity (brain, skeletal muscle, adipose tissues, and intestines) to better understand what effects of GSE extract are mediated by PPARβ/δ and what implication have the GSE extract on the AMPK-PPARβ/δ pathway in animal models of IR and metabolic disturbances.…”

“…Thus, the effects in AMPK and PPARβ/δ activation levels elicit by GSE might be derived by generation of endogenous PPARβ/δ ligands in the liver that might protect against IR, type 2 diabetes mellitus, and its associated disorders. 74…”

Specific RNA m6A modification sites in bone marrow mesenchymal stem cells from the jawbone marrow of type 2 diabetes patients with dental implant failure

“… 63 Aguilar-Recarte et al reported that metformin lowers glucose through by inhibiting mitochondrial respiratory chain complex 1 and activating AMP-activated protein kinase (AMPK), which has been recognised as a potential IR-related pathway. 64 Similarly, Entezari et al also showed that AMPK signalling improves insulin sensitivity and prevents oxidative stress and cell death in cells. Entezari et al also showed that AMPK signalling improves insulin sensitivity and prevents oxidative stress and cell death in β cells.…”

Characterization of DNA methylation as well as mico-RNA expression and screening of epigenetic markers in adipogenesis

“…For instance, hsa-miR-455-3p can bind abundant target genes, such as APOBEC3F, BAIAP2, CDKN2A, CLCC1, PFKP, PLPP4, POFUT2, SYT7, and TMEM43. Hsa-miR-455 enhances adipogenic differentiation of 3T3-L1 cells by targeting uncoupling protein-1 [ 29 ]. Hsa-miR-455 activates AMPKα1 by targeting HIF1, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis.…”