PMID- 31326351 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20200622 IS - 2212-8778 (Electronic) IS - 2212-8778 (Linking) VI - 28 DP - 2019 Oct TI - Temporal plasticity of insulin and incretin secretion and insulin sensitivity following sleeve gastrectomy contribute to sustained improvements in glucose control. PG - 144-150 LID - S2212-8778(19)30433-8 [pii] LID - 10.1016/j.molmet.2019.07.003 [doi] AB - OBJECTIVE: Bariatric surgery acutely improves glucose control, an effect that is generally sustained for years in most patients. The acute postoperative glycemic reduction is at least partially mediated by enhanced incretin secretion and islet function, and occurs independent of caloric restriction, whereas the sustained improvement in glucose control is associated with increased insulin sensitivity. However, studies in humans with bariatric surgery suggest that these elevations are not static but undergo coordinated regulation throughout the postoperative time course. The studies described here test the hypothesis that incretin secretion, islet function, and peripheral insulin sensitivity undergo temporal regulation following bariatric surgery as a means to regulate glucose homeostasis. METHODS: Incretin secretion, islet function, and insulin sensitivity in mice with vertical sleeve gastrectomy (VSG) were compared to sham-operated controls that were pair-fed for 90d, matching food consumption and body-weight between groups. RESULTS: Glucose clearance and insulin secretion were enhanced in VSG mice compared to controls during mixed-meal tolerance tests (MMTT) at 12 and 80 days postoperatively, as were prandial GLP-1, GIP, and glucagon levels. Insulin sensitivity was comparable between groups 14d after surgery, but significantly greater in the VSG group at day 75, despite similar body-weight gain between groups. Glucose stimulated insulin secretion was greater in VSG mice compared to controls in vivo (I.P. glucose injection) and ex vivo (islet perifusion) indicating a rapid and sustained enhancement of beta-cell function after surgery. Notably, glycemia following a MMTT was progressively higher over time in the control animals but improved in the VSG mice at 80d despite weight regain. However, meal-stimulated incretin secretion decreased in VSG mice from 10 to 80 days postoperative, as did meal-stimulated and I.P. glucose-stimulated insulin secretion. This occurred over the same time period that insulin sensitivity was enhanced in VSG mice, suggesting postoperative islet output is tightly regulated by insulin demand. CONCLUSIONS: These data demonstrate a dynamic, multifactorial physiology for improved glucose control after VSG, whereby rapidly elevated insulin secretion is complimented by later enhancements in insulin sensitivity. Critically, the glucose lowering effect of VSG is demonstrably larger than that of caloric-restriction, suggesting these adaptations are mediated by surgical modification of gastrointestinal anatomy and not weight-loss per se. CI - Copyright (c) 2019 The Authors. Published by Elsevier GmbH.. All rights reserved. FAU - Douros, Jonathan D AU - Douros JD AD - Division of Endocrinology, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. Electronic address: jonathan.douros@duke.edu. FAU - Niu, Jingjing AU - Niu J AD - Division of Endocrinology, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. FAU - Sdao, Sophia AU - Sdao S AD - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA. FAU - Gregg, Trillian AU - Gregg T AD - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA. FAU - Merrins, Matthew J AU - Merrins MJ AD - Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin-Madison, Madison, WI, USA. FAU - Campbell, Jonathan AU - Campbell J AD - Division of Endocrinology, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. FAU - Tong, Jenny AU - Tong J AD - Division of Endocrinology, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. FAU - D'Alessio, David AU - D'Alessio D AD - Division of Endocrinology, Duke Molecular Physiology Institute, Duke University, Durham, NC, USA. LA - eng GR - R01 DK113103/DK/NIDDK NIH HHS/United States GR - R21 AG050135/AG/NIA NIH HHS/United States GR - T32 DK007012/DK/NIDDK NIH HHS/United States GR - R01 AG062328/AG/NIA NIH HHS/United States GR - F32 DK115031/DK/NIDDK NIH HHS/United States GR - R01 DK097550/DK/NIDDK NIH HHS/United States GR - R01 DK057900/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190705 PL - Germany TA - Mol Metab JT - Molecular metabolism JID - 101605730 RN - 0 (Blood Glucose) RN - 0 (Incretins) RN - 0 (Insulin) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Blood Glucose/*metabolism MH - Calcium/metabolism MH - *Gastrectomy MH - Glucose Tolerance Test MH - Incretins/*metabolism MH - Insulin/*metabolism MH - Insulin Resistance MH - Mice MH - Mice, Inbred C57BL MH - *Neuronal Plasticity PMC - PMC6822258 OTO - NOTNLM OT - Bariatric surgery OT - Incretin OT - Insulin secretion OT - Insulin sensitivity OT - Islet function EDAT- 2019/07/22 06:00 MHDA- 2020/06/23 06:00 PMCR- 2019/07/05 CRDT- 2019/07/22 06:00 PHST- 2019/05/14 00:00 [received] PHST- 2019/06/19 00:00 [revised] PHST- 2019/07/02 00:00 [accepted] PHST- 2019/07/22 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/07/22 06:00 [entrez] PHST- 2019/07/05 00:00 [pmc-release] AID - S2212-8778(19)30433-8 [pii] AID - 10.1016/j.molmet.2019.07.003 [doi] PST - ppublish SO - Mol Metab. 2019 Oct;28:144-150. doi: 10.1016/j.molmet.2019.07.003. Epub 2019 Jul 5.