The interrelation between aPKC and glucose uptake in the skeletal muscle during contraction and insulin stimulation

Abstract

Contraction and insulin increase glucose uptake in skeletal muscle. While the insulin pathway, better characterized, requires activation of phosphoinositide 3-kinase (PI3K) and atypical protein kinase (aPKC), muscle contraction seems to share insulin-activated components to increase glucose uptake. This study aimed to investigate the interrelation between the pathway involved in glucose uptake evoked by insulin and muscle contraction. Isolated muscle of rats was treated with solvent (control), insulin, wortmannin (PI3K inhibitor) and the combination of insulin plus wortmannin. After treatment, muscles were electrically stimulated (contracted) or remained at rest. Glucose transporter 4 (GLUT4) localization, glucose uptake and phospho-aPKC (aPKC activated form) were assessed. Muscle contraction and insulin increased glucose uptake in all conditions when compared with controls not stimulating an effect that was accompanied by an increase in GLUT4 and of phospho-aPKC at the muscle membrane. Contracted muscles treated with insulin did not show additive effects on glucose uptake or aPKC activity compared with the response when these stimuli were applied alone. Inhibition of PI3K blocked insulin effect on glucose uptake and aPKC but not in the contractile response. Thus, muscle contraction seems to stimulate aPKC and glucose uptake independently of PI3K. Therefore, aPKC may be a convergence point and a rate limit step in the pathway by which, insulin and contraction, increase glucose uptake in skeletal muscle.

The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective

“…In fact, studies from the last three decades have demonstrated the benefits of exercise and muscle contraction on improving insulin sensitivity [33,40,41]. It is also well known that acute muscle contraction increases glucose uptake by activating GLUT4 translocation in a pathway partially independent to insulin cascade [11] (Figure 3). Two main intracellular mechanisms have been suggested to explain the acute effect of contraction-induced glucose transport.…”

“…It have been suggested in skeletal muscle that the pathway activated by exercise/contraction 10 converge at insulin pathway by activating AS160 and aPKC to facilitate the translocation of GLUT4 ( Figure 3) [11,33,42].…”

“…Insulin controls glucose homeostasis by regulating the translocation of GLUT4, key glucose transporter in skeletal muscle, from the intracellular pool to the plasma membrane [11,30,31]. Insulininduced glucose uptake is a complex mechanism initiated by insulin binding with insulin receptor (IR) that activates the insulin substrate receptor (IRS).…”

“…In fact, studies suggest that exercise could diminish high caloric food intake improving metabolic profile [8,9] and skeletal muscle contraction can increase glucose uptake and lipid peroxidation [10][11][12]. However, the global factors regulating physical exercise-induced changes in skeletal muscle of obese and insulin resistance individuals are unknown.…”

Effects of Type 2 Diabetes Mellitus Induction and of Moderate Physical Exercise on the Hepatic Metabolism and Oxidative Stress in Wistar Rats

“…Diabetes is a growing epidemic expected to reach half of billion worldwide subjects (WHO, 2018). Type 2 Diabetes Mellitus (T2DM) accounts for 90-95% of the de diabetes cases, is a multifactorial disease linked with combined obesity, hyperlipidemia, physical inactivity that leads to the development of insulin resistance (SANTOS et al, 2014). Long periods of hyperglycemia, a common condition of diabetic patients, induces a great number of diabetes complications such as nephropathy, retinopathy, liver diseases and neuropathy (LIU et al, 2017).…”