Molecular Mechanisms of Insulin Resistance in Humans and Their Potential Links With Mitochondrial Dysfunction

By K. Morino, K. Petersen, Gerald I. Shulman. Diabetes, 2006

879 citations recorded by the source corpus.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/4f617c6bd8ba5003e5beff690644ecec83d580de

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Citations in the corpus

Pathogenesis of Insulin Resistance in Skeletal Muscle (2010, background): “The recent studies have reported the existence of a defect in mitochondrial oxidative phosphorylation in skeletal muscle in insulin resistance states [16–20] and suggest that this mitochondrial defect contributes to the increased intramyocellar fat content.”
The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome (2010, background): “Furthermore, the intermediate diacylglycerol, which accumulates during de novo lipogenesis activates hepatic protein kinase C e type (PKCe)”
A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin Resistance (2009, background): “…via glutamate transamination to alanine. contributing to accumulation of lipid-derived metabolites such as diacylglyerols, ceramides, ketones, prostaglandins, and incompletely oxidized lipids that can impact insulin signaling (Muoio and Newgard, 2008; Morino et al., 2006; Summers, 2006).”
PPARs are a unique set of fatty acid regulated transcription factors controlling both lipid metabolism and inflammation (2011, background): “The lipotoxicity theory [14] proposes that when the fat storing capacity of the adipose tissue is chronically overloaded, fatty molecules will be deposited in other tissues, including muscle and liver.”
AMP-Activated Protein Kinase–Deficient Mice Are Resistant to the Metabolic Effects of Resveratrol (2009, background): “Insulin-resistant states are associated with increased production of ROS, and reduction of ROS with antioxidants improves insulin sensitivity (39,40).”
SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function (2012, background): “Skeletal muscle is one of the primary tissues responsible for insulin stimulated glucose uptake and reduced mitochondrial function has been shown to play an important role in the development of insulin resistance with obesity (Morino et al., 2006; Wallace, 2005).”
The Major Green Tea Polyphenol, (−)-Epigallocatechin-3-Gallate, Inhibits Obesity, Metabolic Syndrome, and Fatty Liver Disease in High-Fat–Fed Mice, (2008, background): “These effects may be mediated through the activation of protein kinase C, which is stimulated by fatty acids and contributes to the phosphorylation of the insulin receptor substrate at Ser-307, resulting in inhibition of normal insulin signaling (32,33).”
Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. (2009, background): “We propose that the increased hepatic lipid resulting from fructose-induced DNL leads to hepatic insulin resistance (49, 50), possibly by increasing levels of diacylglycerol (49).”