Christopher E Shannon1,2, Aurora Merovci1, Marcel Fourcaudot1, Devjit Tripathy1,3, Muhammad Abdul-Ghani1, Hu Wang4, Xianlin Han1,4, Luke Norton1, Ralph A DeFronzo1. 1. Division of Diabetes, Department of Medicine, UT Health San Antonio, San Antonio, TX, USA. 2. UCD Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland. 3. Audie L Murphy VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA. 4. Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, TX, USA.
Abstract
CONTEXT: Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (ie, glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear. OBJECTIVE: To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids. DESIGN: Single group pretest-posttest. PARTICIPANTS: Healthy males and females with normal glucose tolerance. INTERVENTIONS: 72-hour glucose infusion raising plasma glucose by ~50 mg/dL. MAIN OUTCOME MEASURES: Skeletal muscle lipids, insulin sensitivity, lipid oxidation. RESULTS: Despite impairing insulin-mediated glucose disposal and suppressing fasting lipid oxidation, hyperglycemia did not alter either the content or composition of skeletal muscle triglycerides, diacylglycerides, or phospholipids. Skeletal muscle ceramides decreased after glucose infusion, likely in response to a reduction in free fatty acid concentrations. CONCLUSIONS: Our results demonstrate that the major lipid pools in skeletal muscle are unperturbed by sustained increases in glucose availability and suggest that glucotoxicity and lipotoxicity drive insulin resistance through distinct mechanistic pathways.
CONTEXT: Sustained increases in plasma glucose promote skeletal muscle insulin resistance independent from obesity and dyslipidemia (ie, glucotoxicity). Skeletal muscle lipids are key molecular determinants of insulin action, yet their involvement in the development of glucotoxicity is unclear. OBJECTIVE: To explore the impact of mild physiologic hyperglycemia on skeletal muscle lipids. DESIGN: Single group pretest-posttest. PARTICIPANTS: Healthy males and females with normal glucose tolerance. INTERVENTIONS: 72-hour glucose infusion raising plasma glucose by ~50 mg/dL. MAIN OUTCOME MEASURES: Skeletal muscle lipids, insulin sensitivity, lipid oxidation. RESULTS: Despite impairing insulin-mediated glucose disposal and suppressing fasting lipid oxidation, hyperglycemia did not alter either the content or composition of skeletal muscle triglycerides, diacylglycerides, or phospholipids. Skeletal muscle ceramides decreased after glucose infusion, likely in response to a reduction in free fatty acid concentrations. CONCLUSIONS: Our results demonstrate that the major lipid pools in skeletal muscle are unperturbed by sustained increases in glucose availability and suggest that glucotoxicity and lipotoxicity drive insulin resistance through distinct mechanistic pathways.
Authors: L H Storlien; D A Pan; A D Kriketos; J O'Connor; I D Caterson; G J Cooney; A B Jenkins; L A Baur Journal: Lipids Date: 1996-03 Impact factor: 1.880
Authors: Giuseppe Daniele; Juan Xiong; Carolina Solis-Herrera; Aurora Merovci; Roy Eldor; Devjit Tripathy; Ralph A DeFronzo; Luke Norton; Muhammad Abdul-Ghani Journal: Diabetes Care Date: 2016-08-25 Impact factor: 19.112
Authors: Chris Shannon; Aurora Merovci; Juan Xiong; Devjit Tripathy; Felipe Lorenzo; Donald McClain; Muhammad Abdul-Ghani; Luke Norton; Ralph A DeFronzo Journal: Diabetes Date: 2018-09-13 Impact factor: 9.461