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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Senolytics improve physical function and increase lifespan in old age

Nature Medicine, Journal Year: 2018, Volume and Issue: 24(8), P. 1246 - 1256

Published: July 6, 2018

Language: Английский

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The multifaceted contributions of mitochondria to cellular metabolism

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(7), P. 745 - 754

Published: June 22, 2018

Language: Английский

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Adipogenesis and metabolic health

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(4), P. 242 - 258

Published: Jan. 4, 2019

Language: Английский

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Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease

Cell Metabolism, Journal Year: 2019, Volume and Issue: 30(4), P. 656 - 673

Published: Aug. 22, 2019

Language: Английский

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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men

Physiological Reviews, Journal Year: 2017, Volume and Issue: 98(1), P. 117 - 214

Published: Dec. 6, 2017

The pancreatic β-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering blood concentration. Impaired insulin secretion results chronic hyperglycemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. healthy acts as sensor matching its output to circulating It does so via metabolically induced changes electrical activity, culminate an increase cytoplasmic Ca2+ concentration and initiation Ca2+-dependent exocytosis insulin-containing secretory granules. Here, we review recent advances our understanding transcriptome, exocytosis. We highlight salient differences between mouse human β-cells, provide models how different ion channels contribute their activity secretion, conclude discussing these processes become perturbed T2DM.

Language: Английский

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Causes, Characteristics, and Consequences of Metabolically Unhealthy Normal Weight in Humans

Cell Metabolism, Journal Year: 2017, Volume and Issue: 26(2), P. 292 - 300

Published: Aug. 1, 2017

Language: Английский

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The obese adipose tissue microenvironment in cancer development and progression

Nature Reviews Endocrinology, Journal Year: 2018, Volume and Issue: 15(3), P. 139 - 154

Published: Nov. 20, 2018

Language: Английский

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Metabolic-associated fatty liver disease and lipoprotein metabolism

Molecular Metabolism, Journal Year: 2021, Volume and Issue: 50, P. 101238 - 101238

Published: April 20, 2021

Non-alcoholic fatty liver disease, or as recently proposed 'metabolic-associated disease' (MAFLD), is characterized by pathological accumulation of triglycerides and other lipids in hepatocytes. This common disease can progress from simple steatosis to steatohepatitis, eventually end-stage diseases. MAFLD closely related disturbances systemic energy metabolism, including insulin resistance atherogenic dyslipidemia. The the central organ lipid metabolism secreting very low density lipoproteins (VLDL) and, on hand, internalizing acids lipoproteins. review article discusses recent research addressing hepatic synthesis, VLDL production, lipoprotein internalization well exchange between adipose tissue context MAFLD. Liver triggered excessive triglyceride synthesis utilizing derived white (WAT), de novo lipogenesis (DNL) endocytosed remnants triglyceride-rich In consequence high content, secretion enhanced, which primary cause complex dyslipidemia typical for subjects with Interventions reducing secretory capacity attenuate while they exacerbate MAFLD, indicating that balance storage versus hepatocytes a critical parameter determining outcome. Proof concept studies have shown promoting combustion tissues reduces load thus ameliorates Moreover, hepatocellular DNL WAT-derived be targeted treat However, more needed understand how individual transporters, enzymes, their isoforms affect vivo, whether these two aspects selectively treated. Processing cholesterol-enriched appears less important steatosis. It may, however, modulate inflammation consequently progression.

Language: Английский

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The science of plant‐based foods: Constructing next‐generation meat, fish, milk, and egg analogs

Comprehensive Reviews in Food Science and Food Safety, Journal Year: 2021, Volume and Issue: 20(4), P. 4049 - 4100

Published: May 30, 2021

Abstract Consumers are increasingly demanding foods that more ethical, sustainable and nutritious to improve the health of themselves planet. The food industry is currently undergoing a revolution, as both small large companies pivot toward creation new generation plant‐based products meet this consumer demand. In particular, there an emphasis on production mimic those omnivores familiar with, such meat, fish, egg, milk, their products. main challenge in area simulate desirable appearance, texture, flavor, mouthfeel, functionality these using ingredients isolated entirely from botanical sources, proteins, carbohydrates, lipids. molecular, chemical, physical properties plant‐derived usually very different animal‐derived ones. It therefore critical understand fundamental how they can be assembled into structures resembling found animal This review article provides overview current status scientific understanding highlights areas where further research required. it focuses physical, functional ingredients; processing operations used convert products; and, science behind formulation vegan eggs, milk alternatives.

Language: Английский

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