PMID- 26324180 OWN - NLM STAT- MEDLINE DCOM- 20160428 LR - 20181202 IS - 1939-327X (Electronic) IS - 0012-1797 (Print) IS - 0012-1797 (Linking) VI - 65 IP - 1 DP - 2016 Jan TI - Mechanism by Which Caloric Restriction Improves Insulin Sensitivity in Sedentary Obese Adults. PG - 74-84 LID - 10.2337/db15-0675 [doi] AB - Caloric restriction (CR) improves insulin sensitivity and reduces the incidence of diabetes in obese individuals. The underlying mechanisms whereby CR improves insulin sensitivity are not clear. We evaluated the effect of 16 weeks of CR on whole-body insulin sensitivity by pancreatic clamp before and after CR in 11 obese participants (BMI = 35 kg/m(2)) compared with 9 matched control subjects (BMI = 34 kg/m(2)). Compared with the control subjects, CR increased the glucose infusion rate needed to maintain euglycemia during hyperinsulinemia, indicating enhancement of peripheral insulin sensitivity. This improvement in insulin sensitivity was not accompanied by changes in skeletal muscle mitochondrial oxidative capacity or oxidant emissions, nor were there changes in skeletal muscle ceramide, diacylglycerol, or amino acid metabolite levels. However, CR lowered insulin-stimulated thioredoxin-interacting protein (TXNIP) levels and enhanced nonoxidative glucose disposal. These results support a role for TXNIP in mediating the improvement in peripheral insulin sensitivity after CR. CI - (c) 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. FAU - Johnson, Matthew L AU - Johnson ML AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Distelmaier, Klaus AU - Distelmaier K AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Lanza, Ian R AU - Lanza IR AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Irving, Brian A AU - Irving BA AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Robinson, Matthew M AU - Robinson MM AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Konopka, Adam R AU - Konopka AR AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN. FAU - Shulman, Gerald I AU - Shulman GI AD - Howard Hughes Medical Institute and the Departments of Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT. FAU - Nair, K Sreekumaran AU - Nair KS AD - Division of Endocrinology and Metabolism, Mayo Clinic College of Medicine, Rochester, MN nair@mayo.edu. LA - eng GR - R01 DK049230/DK/NIDDK NIH HHS/United States GR - R01 DK041973/DK/NIDDK NIH HHS/United States GR - R01 DK059615/DK/NIDDK NIH HHS/United States GR - UL1-TR-000135/TR/NCATS NIH HHS/United States GR - T32-DK-007352/DK/NIDDK NIH HHS/United States GR - R24-DK-090963/DK/NIDDK NIH HHS/United States GR - T32 DK007198/DK/NIDDK NIH HHS/United States GR - R24 DK090963/DK/NIDDK NIH HHS/United States GR - P30 DK050456/DK/NIDDK NIH HHS/United States GR - DK-50456/DK/NIDDK NIH HHS/United States GR - KL2 TR000136/TR/NCATS NIH HHS/United States GR - KL2 RR024151/RR/NCRR NIH HHS/United States GR - U24 DK100469/DK/NIDDK NIH HHS/United States GR - R01-DK-41973/DK/NIDDK NIH HHS/United States GR - T32-DK-007198/DK/NIDDK NIH HHS/United States GR - UL1 TR000135/TR/NCATS NIH HHS/United States GR - Howard Hughes Medical Institute/United States GR - R01-DK-49230/DK/NIDDK NIH HHS/United States GR - T32 DK007352/DK/NIDDK NIH HHS/United States GR - KL2-RR-024151/RR/NCRR NIH HHS/United States GR - U24-DK-100469/DK/NIDDK NIH HHS/United States GR - KL2-TR-000136-07/TR/NCATS NIH HHS/United States GR - R56 DK041973/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150831 PL - United States TA - Diabetes JT - Diabetes JID - 0372763 RN - 0 (Amino Acids) RN - 0 (Blood Glucose) RN - 0 (Carrier Proteins) RN - 0 (Ceramides) RN - 0 (Diglycerides) RN - 0 (TXNIP protein, human) RN - BBX060AN9V (Hydrogen Peroxide) SB - IM CIN - Diabetes. 2016 Jan;65(1):16-8. PMID: 26696635 MH - Amino Acids/metabolism MH - Blood Glucose/*metabolism MH - Blotting, Western MH - *Caloric Restriction MH - Calorimetry, Indirect MH - Carrier Proteins/genetics/metabolism MH - Case-Control Studies MH - Ceramides/metabolism MH - Diglycerides/metabolism MH - Energy Metabolism MH - Female MH - Glucose Clamp Technique MH - Humans MH - Hydrogen Peroxide/metabolism MH - *Insulin Resistance MH - Male MH - Middle Aged MH - Mitochondria, Muscle/*metabolism MH - Muscle, Skeletal/*metabolism MH - Obesity/diet therapy/genetics/*metabolism MH - Oxidation-Reduction MH - *Sedentary Behavior PMC - PMC4686951 EDAT- 2015/09/02 06:00 MHDA- 2016/04/29 06:00 PMCR- 2017/01/01 CRDT- 2015/09/02 06:00 PHST- 2015/05/20 00:00 [received] PHST- 2015/08/26 00:00 [accepted] PHST- 2015/09/02 06:00 [entrez] PHST- 2015/09/02 06:00 [pubmed] PHST- 2016/04/29 06:00 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - db15-0675 [pii] AID - 0675 [pii] AID - 10.2337/db15-0675 [doi] PST - ppublish SO - Diabetes. 2016 Jan;65(1):74-84. doi: 10.2337/db15-0675. Epub 2015 Aug 31.