Insulin resistance: Review of the underlying molecular mechanisms

• Published in: Journal of cellular physiology Vol. 234; no. 6; pp. 8152 - 8161
• Main Authors: Yaribeygi, Habib, Farrokhi, Farin Rashid, Butler, Alexandra E., Sahebkar, Amirhossein
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.06.2019
• Subjects: Adipocytes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Glucose; Glucose - metabolism; GLUT‐4; Humans; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Insulin; Insulin - metabolism; insulin receptor substrate; Insulin resistance; Insulin Resistance - genetics; insulin sensitivity; insulin signaling; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - genetics; Metabolic Syndrome - metabolism; Metabolic Syndrome - pathology; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondria - pathology; Molecular modelling; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscles; Mutation; Oxidative stress; Oxidative Stress - genetics; Signal Transduction - genetics; Signaling; Skeletal muscle; Substrates; TNF‐α; insulin sensitivity; insulin signaling; TNF-α; GLUT-4; diabetes mellitus; insulin receptor substrate; insulin resistance; oxidative stress
• ISSN: 0021-9541; 1097-4652; 1097-4652
• DOI: 10.1002/jcp.27603

Most human cells utilize glucose as the primary substrate, cellular uptake requiring insulin. Insulin signaling is therefore critical for these tissues. However, decrease in insulin sensitivity due to the disruption of various molecular pathways causes insulin resistance (IR). IR underpins many metabolic disorders such as type 2 diabetes and metabolic syndrome, impairments in insulin signaling disrupting entry of glucose into the adipocytes, and skeletal muscle cells. Although the exact underlying cause of IR has not been fully elucidated, a number of major mechanisms, including oxidative stress, inflammation, insulin receptor mutations, endoplasmic reticulum stress, and mitochondrial dysfunction have been suggested. In this review, we consider the role these cellular mechanisms play in the development of IR.