Mechanisms of Insulin Action and Insulin Resistance

Physiological Reviews, Journal Year: 2018, Volume and Issue: 98(4), P. 2133 - 2223

Published: Aug. 1, 2018

The 1921 discovery of insulin was a Big Bang from which vast and expanding universe research into action resistance has issued. In the intervening century, some discoveries have matured, coalescing solid fertile ground for clinical application; others remain incompletely investigated scientifically controversial. Here, we attempt to synthesize this work guide further mechanistic investigation inform development novel therapies type 2 diabetes (T2D). rational such necessitates detailed knowledge one key pathophysiological processes involved in T2D: resistance. Understanding resistance, turn, requires normal action. review, both physiology pathophysiology are described, focusing on three target tissues: skeletal muscle, liver, white adipose tissue. We aim develop an integrated physiological perspective, placing intricate signaling effectors that carry out cell-autonomous response context tissue-specific functions generate coordinated organismal response. First, section II, effects direct, tissue reviewed, beginning at receptor working downstream. Section III considers critical underappreciated role crosstalk whole body action, especially essential interaction between lipolysis hepatic gluconeogenesis. is then described IV. Special attention given pathways become resistant setting chronic overnutrition, alternative explanation phenomenon ‟selective resistanceˮ presented. Sections V, VI, VII critically examine evidence against several putative mediators V reviews linking bioactive lipids diacylglycerol, ceramide, acylcarnitine resistance; VI impact nutrient stresses endoplasmic reticulum mitochondria discusses non-cell autonomous factors proposed induce including inflammatory mediators, branched-chain amino acids, adipokines, hepatokines. Finally, VIII, propose model links these final common metabolite-driven gluconeogenesis ectopic lipid accumulation.

Language: Английский

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AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance

Molecular Cell, Journal Year: 2017, Volume and Issue: 66(6), P. 789 - 800

Published: June 1, 2017

Language: Английский

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Metabolism of inflammation limited by AMPK and pseudo-starvation

Nature, Journal Year: 2013, Volume and Issue: 493(7432), P. 346 - 355

Published: Jan. 15, 2013

Language: Английский

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Adipose tissue browning and metabolic health

Nature Reviews Endocrinology, Journal Year: 2013, Volume and Issue: 10(1), P. 24 - 36

Published: Oct. 22, 2013

Language: Английский

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Adapting to obesity with adipose tissue inflammation

Nature Reviews Endocrinology, Journal Year: 2017, Volume and Issue: 13(11), P. 633 - 643

Published: Aug. 11, 2017

Language: Английский

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AMPK: Sensing Glucose as well as Cellular Energy Status

Cell Metabolism, Journal Year: 2017, Volume and Issue: 27(2), P. 299 - 313

Published: Nov. 16, 2017

Language: Английский

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Regulation and function of AMPK in physiology and diseases

Experimental & Molecular Medicine, Journal Year: 2016, Volume and Issue: 48(7), P. e245 - e245

Published: July 15, 2016

5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine that was originally identified as the key player in maintaining cellular energy homeostasis. Intensive research over last decade has diverse molecular mechanisms and physiological conditions regulate AMPK activity. regulates metabolic processes dysregulated major chronic diseases, such obesity, inflammation, diabetes cancer. On basis of its critical roles physiology pathology, emerging one most promising targets for both prevention treatment these diseases. In this review, we discuss current understanding regulation functions. addition, underlying versatile Therapies based on enzyme involved balance may help prevent treat cancer, obesity diabetes. Sang-Min Jeon at Ajou University Suwon, South Korea, reviewed ‘5’-AMP-activated kinase' (AMPK), potential to Among other tasks, maintains cells by regulating glucose levels oxidizing fatty acids. Research indicates are suppressed over-eating, triggering insulin resistance hence Reducing can also induce a component diseases like Jeon's review finds evidence activating patients could progression A similar technique fight early-stage carcinogenesis. However, warns exacerbate later-stage carcinogenesis established cancer tumors.

Language: Английский

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TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop

Nature Cell Biology, Journal Year: 2013, Volume and Issue: 15(6), P. 647 - 658

Published: April 19, 2013

Language: Английский

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Spermidine in health and disease

Science, Journal Year: 2018, Volume and Issue: 359(6374)

Published: Jan. 25, 2018

Having your longevity and eating too Although caloric restriction has clear benefits for maximizing health span life span, it is sufficiently unpleasant that few humans stick to it. Madeo et al. review evidence increased intake of the polyamine spermidine appears reproduce many healthful effects restriction, they explain its cellular actions, which include enhancement autophagy protein deacetylation. Spermidine found in foods such as wheat germ, soybeans, nuts, some fruits vegetables produced by microbiota. Increased uptake protective against cancer, metabolic disease, heart neurodegeneration. Science , this issue p. eaan2788

Language: Английский

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AMPK, insulin resistance, and the metabolic syndrome

Journal of Clinical Investigation, Journal Year: 2013, Volume and Issue: 123(7), P. 2764 - 2772

Published: June 30, 2013

Insulin resistance (IR) and hyperinsulinemia are hallmarks of the metabolic syndrome, as central adiposity, dyslipidemia, a predisposition to type 2 diabetes, atherosclerotic cardiovascular disease, hypertension, certain cancers. Regular exercise calorie restriction have long been known increase insulin sensitivity decrease prevalence these disorders. The subsequent identification AMP-activated protein kinase (AMPK) its activation by fuel deprivation led studies effects AMPK on both IR syndrome–related diseases. In this review, we evaluate body literature, with special emphasis hypothesis that dysregulation is pathogenic factor for disorders in humans target their prevention therapy.

Language: Английский

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