Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease
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INVITED REVIEW
Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease Alexandra Chadt 1,2 & Hadi Al-Hasani 1,2 Received: 21 February 2020 / Revised: 1 June 2020 / Accepted: 5 June 2020 # The Author(s) 2020
Abstract A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific glucose uptake and metabolism in the liver, skeletal muscle, and adipose tissue to ensure homeostatic control of blood glucose levels. Reduced glucose transport activity results in aberrant use of energy substrates and is associated with insulin resistance and type 2 diabetes. It is well established that GLUT2, the main regulator of hepatic hexose flux, and GLUT4, the workhorse in insulin- and contraction-stimulated glucose uptake in skeletal muscle, are critical contributors in the control of whole-body glycemia. However, the molecular mechanism how insulin controls glucose transport across membranes and its relation to impaired glycemic control in type 2 diabetes remains not sufficiently understood. An array of circulating metabolites and hormone-like molecules and potential supplementary glucose transporters play roles in fine-tuning glucose flux between the different organs in response to an altered energy demand. Keywords Crosstalk . Exercise . Insulin resistance . NAFLD . Type 2 diabetes
Introduction Glucose represents the major source of energy for most tissues of the body. Thus, maintenance of whole-body glucose homeostasis is the result of a complex regulatory system involving various tissues. Inter-organ crosstalk via a diversity of circulating factors such as hormones and neuropeptides ensures distribution of nutritional components according to the respective need of the specific organ [84]. At present, three classes of eukaryotic sugar transporters have been characterized: glucose transporters (GLUTs) belonging to the SLC2A gene family, sodium-glucose symporters (SGLTs), and SWEETs [32]. The large family of GLUTs, evolutionary conserved facilitative glucose transporters, is involved in all Contribution to the Special Issue on “Glucose transporters in health and disease,” edited by Hermann Koepsell and Volker Vallon * Hadi Al-Hasani [email protected] 1
Medical Faculty, Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany
2
German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
critical steps of handling glucose and other hexoses, including absorption, distribution, and excretion/recovery. Intake of carbohydrates leads to an immediate increase in circulating blood glucose levels after absorption of the glucose from the intestine. As a direct response, pancreatic beta cells sense the elevated blood glucose concentrations via a GLUT2-dependent process and increase secretion of insulin. Consequently, insulin binding to its receptors leads to enhanced glucose transport into skeletal mu
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