The Role of Glucose and Fatty Acid Metabolism in the Development of Insulin Resistance in Skeletal Muscle

Abstract

The rapid rise in the prevalence of obesity and diabetes has significantly contributed to the increasing global burden of noncommunicable diseases. Insulin resistance is a major underpinning etiology of both obesity and type 2 diabetes. Insulin resistance is characterized by a reduced response of skeletal, liver, and fat tissues to the actions of insulin hormone. Although detailed mechanisms implicated in the development of insulin resistance remain plausible, skeletal muscles have been identified to play an integral role in the improvement of insulin sensitivity in the diseased state. The effective modulation of glucose and fatty acid metabolism in the skeletal muscle through exercise or by certain therapeutics has been associated with reversal of insulin resistance and amelioration of diabetes associated complications such as inflammation and oxidative stress. This chapter will briefly discuss the role of glucose and fatty acid metabolism in the development of insulin resistance in the skeletal muscle.

Bioactive compounds of African star apple (Chrysophyllum albidumG. Don) and its modulatory effect on metabolic activities linked to type 2 diabetes in isolated rat psoas muscle

“…It is characterized by insulin resistance leading to impaired glucose uptake and utilization by the skeletal muscles. Skeletal muscles utilize glucose and free fatty acids (FFAs) as its main source of energy (Mazibuko‐Mbeje et al., 2018). In the fasting state, glucose uptake is diminished in skeletal muscles owing to the downregulation of GLUT‐4 which leads to a switch to FFAs for ATP production (Salau et al., 2020).…”

“…In the fasting state, glucose uptake is diminished in skeletal muscles owing to the downregulation of GLUT‐4 which leads to a switch to FFAs for ATP production (Salau et al., 2020). This is reversed on increased blood glucose level in the fed state, owing to the pancreatic secretion of insulin leading to the upregulation of GLUT‐4 (Mazibuko‐Mbeje et al., 2018). However, in T2D muscle‐glucose uptake is impaired owing to downregulation of GLUT‐4 arising from insulin resistance.…”

A Review on the Antidiabetic Properties of Moringa oleifera Extracts: Focusing on Oxidative Stress and Inflammation as Main Therapeutic Targets

“…Literature suggests that effective modulation of energy metabolism and insulin signaling through the regulation of AMP-activated protein kinase (AMPK) or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathways appears to reverse some devastating outcomes of diabetes ( Long and Zierath, 2006 ; Huang et al, 2018 ; Mazibuko-Mbeje et al, 2018 ). In fact, plants and their related bioactive compounds are increasingly screened for their antidiabetic properties.…”

Overweight and Obese Adult Patients Show Larger Benefits from Concurrent Training Compared with Pharmacological Metformin Treatment on Insulin Resistance and Fat Oxidation

“…Physical inactivity and a poor diet (e.g., excessive content of fat and carbohydrates) have been associated with an increased risk of developing IR [ 6 ]. One of the characteristics of IR is attributed to metabolic inflexibility, a concept related to the poor utilization of glucose and fatty acids [ 6 , 7 ].…”

“…Physical inactivity and a poor diet (e.g., excessive content of fat and carbohydrates) have been associated with an increased risk of developing IR [ 6 ]. One of the characteristics of IR is attributed to metabolic inflexibility, a concept related to the poor utilization of glucose and fatty acids [ 6 , 7 ]. Kelley et al (1999) reported that with obesity, IR derives not only from the absorption of fatty acids, but also from the metabolic inflexibility for fat oxidation, which favors the accumulation of triglycerides in the skeletal muscle [ 7 ].…”