Influence of Acute and Chronic Exercise on Glucose Uptake

Abstract

Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role.

Figure 1

Interaction of important key players in exercise mediated glucose uptake of human muscle cells. A proposed model for the key players in glucose transport after physical exercise. αPKC, atypical PKC; AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; AS160, Akt substrate of 160 kDa; Ca, calcium; CaMKII, Ca²⁺/calmodulin-dependent protein kinase 2; Cr, creatine; GLUT-4, glucose transporter 4; HDAC4/5, histone deacetylase 4/5; IL-6, interleukin 6; IRS-1, insulin receptor substrate 1; LKB-1, liver kinase B1; MEF2, myocyte enhancer factor-2; MAPK, mitogen-activated protein kinases; mTOR, mammalian target of rapamycin (C1 complex 1 and C2 complex 2); PDK, phosphoinositide-dependent kinase; PI3-K, phosphoinositide 3-kinase; PKB, protein kinase B; Rac1, ras-related C3 botulinum toxin substrate 1; TBC1D1, TBC1 domain family member 1; TNF-α, tumor necrosis factor alpha; WAT, white adipose tissue.