General aspects of muscle glucose uptake

Abstract

Glucose uptake in peripheral tissues is dependent on the translocation of GLUT4 glucose transporters to the plasma membrane. Studies have shown the existence of two major signaling pathways that lead to the translocation of GLUT4. The first, and widely investigated, is the insulin activated signaling pathway through insulin receptor substrate-1 and phosphatidylinositol 3-kinase. The second is the insulin-independent signaling pathway, which is activated by contractions. Individuals with type 2 diabetes mellitus have reduced insulin-stimulated glucose uptake in skeletal muscle due to the phenomenon of insulin resistance. However, those individuals have normal glucose uptake during exercise. In this context, physical exercise is one of the most important interventions that stimulates glucose uptake by insulin-independent pathways, and the main molecules involved are adenosine monophosphate-activated protein kinase, nitric oxide, bradykinin, AKT, reactive oxygen species and calcium. In this review, our main aims were to highlight the different glucose uptake pathways and to report the effects of physical exercise, diet and drugs on their functioning. Lastly, with the better understanding of these pathways, it would be possible to assess, exactly and molecularly, the importance of physical exercise and diet on glucose homeostasis. Furthermore, it would be possible to assess the action of drugs that might optimize glucose uptake and consequently be an important step in controlling the blood glucose levels in diabetic patients, in addition to being important to clarify some pathways that justify the development of drugs capable of mimicking the contraction pathway.

Structure of, and functional insight into the GLUT family of membrane transporters

“…210 In many studies, GLUT4 was also found to be associated with type 2 diabetes. 142 While the expression level of GLUT4 did not change in type 2 diabetic rodents, trafficking of GLUT4 was affected in these animals. 210,211 It has also been reported that the pattern of GLUT expression in cartilage changes in the presence of joint disease, offering a possible tool for diagnosis and ultimately treatment.…”

“…6,98,131,[140][141][142] Consequently, we will simply outline some of the key features of the GLUT4 trafficking process. Cushman and Wardzala 143 proposed the first schematic mechanism of how insulin stimulates GLUT translocation to and from the membrane in the rat adipose cell in 1980.…”

“…Subsequently, numerous potential pathways involved in the insulin-dependent pathway have been identified. 140,142 They include insulin receptor substrate, PI3K …”

Obesity and related consequences to ageing

“…Changes in skeletal muscle are important because muscle is essential for locomotion and is the major site of insulin-mediated glucose uptake (Alvim et al 2015). Although physical exercise is considered to be an anti-ageing therapy, weight loss in obese older adults is still heavily debated due to the potential loss of skeletal muscle or bone mass.…”

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

“…It serves to stimulate glucose uptake and metabolism in peripheral tissues. Skeletal muscle is one of the important tissues for whole-body insulin-mediated glucose disposal in the postprandial state [6,7], and is, therefore, the most important site for whole-body glucose homeostasis. It is known that in subjects with T2DM, essentially all the impairment in insulin-mediated glucose disposal is caused by inadequate glucose uptake by muscle [8].…”