Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

By V. Samuel, Gerald I. Shulman. Cell, 2012

2,256 citations recorded by the source corpus.

Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance.

Subfields: Biochemistry, Cell Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/112ff0dc873d1cd99e0f214cfb9540ccfec40f23

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Citations in the corpus

Inflammation, Defective Insulin Signaling, and Mitochondrial Dysfunction as Common Molecular Denominators Connecting Type 2 Diabetes to Alzheimer Disease (2014, background): “Knowledge of the molecular mechanism(s) of defective insulin signaling has increased tremendously during the past decades (24,25).”
Metabolic Inflammation and Insulin Resistance in Obesity (2020, background): “DOI: 10.1161/CIRCRESAHA.119.315896 May 22, 2020 1559 Anti-Inflammatory Thrombosis Outcomes Study) did not show long-term benefits in reducing HbA1c and reductions in incident T2DM.186 The potential of other therapies targeting the NLRP3 inflammasome pathway in treating T2DM remains to be assessed.”
Non-Alcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases (2017, positive): “Following a meal, the relatively high concentrations of insulin within the portal vein ( 33 peripheral vein) directly activate hepatic insulin receptor tyrosine kinase (IRTK) activity, initiating a coordinated relay of intracellular signals (Figure 1) (Samuel and Shulman, 2012).”
Chronic Adipose Tissue Inflammation Linking Obesity to Insulin Resistance and Type 2 Diabetes (2020, background): “Frontiers in Physiology | www.frontiersin.org 6 January 2020 | Volume 10 | Article 1607 They are suggested to be the major source of pro-inflammatory cytokines (Samuel and Shulman, 2012), which can cause IR (Xu et al., 2003).”
Mechanisms of Hepatic Triglyceride Accumulation in Nonalcoholic Fatty Liver Disease (2013, neutral): “Studies in human NAFLD patients have yielded mixed results with respect to alterations in rates of fatty acid oxidation [38].”
Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes (2015, neutral): “Fasting hyperglycemia, due to increased rates of hepatic gluconeogenesis, and the inability of insulin to suppress this process are the hallmark of T2D, but the molecular mechanism for this alteration is unknown (Kahn et al., 2014; Olefsky and Glass, 2010; Robbins et al., 2014; Samuel and Shulman, 2”