Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity

Abstract

Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis. A single bout of exercise has long been known to increase glucose disposal in skeletal muscle in response to physiological insulin concentrations. While this effect is identified to be restricted to the previously exercised muscle, the molecular basis for an apparent convergence between exercise- and insulin-induced signaling pathways is incompletely known. In recent years, we and others have identified the Rab GTPase-activating protein, TBC1 domain family member 4 (TBC1D4) as a target of key protein kinases in the insulin- and exercise-activated signaling pathways. Our working hypothesis is that the AMP-activated protein kinase (AMPK) is important for the ability of exercise to insulin sensitize skeletal muscle through TBC1D4. Here, we aim to provide an overview of the current available evidence linking AMPK to post-exercise insulin sensitivity.

Effect of a Low-Carbohydrate High-Fat Diet and a Single Bout of Exercise on Glucose Tolerance, Lipid Profile and Endothelial Function in Normal Weight Young Healthy Females

“…The positive effect of exercise on fasting glucose and AUC glucose seen 14 h after a bout of exercise was not accompanied by significant changes in fasting insulin, or in AUC insulin. This might be linked to AMPK, which is thought to be important for the ability of exercise to increase GLUT4 translocation and insulin sensitivity in skeletal muscle (Cartee, 2015a;Kjøbsted et al, 2016), as exercise increases glucose disposal in response to physiological insulin concentrations.…”

Dicarbonyl Stress and Glyoxalase-1 in Skeletal Muscle: Implications for Insulin Resistance and Type 2 Diabetes

“…Furthermore, individuals at risk for developing T2DM (obese, insulin-resistant individuals) can reduce the risk of progression to T2DM by over 50% with a lifestyle intervention that focuses on reducing calorie intake and increasing exercise ( 2 ). At this time, the signaling mechanisms that underline these metabolic improvements are not well understood but may involve regulation of GLO1 such as exercise-induced stimuli increase NRF2 ( 64 ), including oxidative stress ( 107 ) and AMPK signaling ( 108 ). It is reasonable to infer that NRF2 directs upregulation of skeletal muscle GLO1 gene in response to these or other exercise-mediated skeletal muscle stimuli.…”

Serine/threonine protein phosphatase 5 is a potential therapeutic target in cholangiocarcinoma

“…Under stress and energy deprivation, AMP and ADP bind to AMPK, causing phosphorylation at Thr 172 and leading to AMPK activation . Moreover, AMPK activation is negatively controlled by phosphatases, namely, PP2A and PP2C, by dephosphorylation at Thr 172 . The data presented here suggest that PP5 also dephosphorylates AMPK at Thr 172.…”