PMID- 31870938 OWN - NLM STAT- MEDLINE DCOM- 20210208 LR - 20210208 IS - 1873-5169 (Electronic) IS - 0196-9781 (Linking) VI - 125 DP - 2020 Mar TI - Endogenously released GIP reduces and GLP-1 increases hepatic insulin extraction. PG - 170231 LID - S0196-9781(19)30209-8 [pii] LID - 10.1016/j.peptides.2019.170231 [doi] AB - GIP was proposed to play a key role in the development of non- alcoholic fatty liver disease (NAFLD) in response to sugar intake. Isomaltulose, is a 1,6-linked glucose-fructose dimer which improves glucose homeostasis and prevents NAFLD compared to 1,2-linked sucrose by reducing glucose-dependent insulinotropic peptide (GIP) in mice. We compared effects of sucrose vs. isomaltulose on GIP and glucagon-like peptide-1 (GLP-1) secretion, hepatic insulin clearance (HIC) and insulin sensitivity in normal (NGT), impaired glucose tolerant (IGT) and Type 2 diabetes mellitus (T2DM) participants. A randomized crossover study was performed in 15 NGT, 10 IGT and 10 T2DM subjects. In comparison to sucrose, peak glucose concentrations were reduced by 2.3, 2.1 and 2.5 mmol/l (all p < 0.05) and insulin levels were 88% (p < 0.01, NGT), 32% (p < 0.05, IGT) and 55% (T2DM) lower after the isomaltulose load. Postprandial GIP(iAUC) concentrations were decreased (56%, p < 0.01 in NGT; 42%, p < 0.05 in IGT and 40%,p < 0.001 in T2DM) whereas GLP-1(iAUC) was 77%, 85% and 85% higher compared to sucrose (p < 0.01), respectively. This resulted in approximately 35 - 50% improved insulin sensitivity and reduced insulinogenic index after isomaltulose, which correlated closely with improved HIC, respectively (r = 0.62, r=-0.70; p < 0.001). HIC was inversely related to GIP (r=-0.44, p < 0.001) and positively related to GLP-1 levels (r = 0.40, p = 0.001). CONCLUSION: Endogenously released GIP correlated with reduced, and GLP-1 with increased hepatic insulin extraction. Increased peripheral insulin levels may contribute to insulin resistance and obesity. We propose that the unfavorable effects of high glycemic index Western diets are related to increased GIP-release and reduced HIC. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Keyhani-Nejad, Farnaz AU - Keyhani-Nejad F AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany. FAU - Barbosa Yanez, Renate Luisa AU - Barbosa Yanez RL AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany; German Center for Diabetes Research, Partner Potsdam, Berlin, Germany. FAU - Kemper, Margrit AU - Kemper M AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany; German Center for Diabetes Research, Partner Potsdam, Berlin, Germany. FAU - Schueler, Rita AU - Schueler R AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany. FAU - Pivovarova-Ramich, Olga AU - Pivovarova-Ramich O AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany; German Center for Diabetes Research, Partner Potsdam, Berlin, Germany; Reseach Group Molecular Nutritional Medicine, Dept. of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. FAU - Rudovich, Natalia AU - Rudovich N AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany; German Center for Diabetes Research, Partner Potsdam, Berlin, Germany; Division of Endocrinology and Diabetes, Department of Internal Medicine, Spital Bulach, 8180, Bulach, Switzerland. FAU - Pfeiffer, Andreas F H AU - Pfeiffer AFH AD - Department of Clinical Nutrition, German Institute of Human Nutrition, Nuthetal, Germany; Department for Endocrinology, Diabetes and Nutrition, Charite - University of Medicine, Berlin, Germany; German Center for Diabetes Research, Partner Potsdam, Berlin, Germany. Electronic address: afhp@charite.de. LA - eng PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20191220 PL - United States TA - Peptides JT - Peptides JID - 8008690 RN - 0 (Incretins) RN - 0 (Insulin) RN - 57-50-1 (Sucrose) RN - 59392-49-3 (Gastric Inhibitory Polypeptide) RN - 67I334IX2M (Isomaltose) RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - V59P50X4UY (isomaltulose) SB - IM MH - Adult MH - Case-Control Studies MH - Cross-Over Studies MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism/pathology MH - Female MH - Gastric Inhibitory Polypeptide/*pharmacology MH - Glucagon-Like Peptide 1/*pharmacology MH - Humans MH - Incretins/*pharmacology MH - Insulin/*metabolism MH - *Insulin Resistance MH - Isomaltose/administration & dosage/analogs & derivatives MH - Liver/drug effects/*metabolism MH - Male MH - Middle Aged MH - Sucrose/administration & dosage OTO - NOTNLM OT - GIP OT - Glucose-dependent insulinotropic peptide OT - Glycemic index OT - Hepatic insulin clearance OT - Isomaltulose OT - Sucrose COIS- Declaration of Competing Interest The authors have no conflict of interest to disclose. EDAT- 2019/12/25 06:00 MHDA- 2021/02/09 06:00 CRDT- 2019/12/25 06:00 PHST- 2019/09/04 00:00 [received] PHST- 2019/12/05 00:00 [revised] PHST- 2019/12/07 00:00 [accepted] PHST- 2019/12/25 06:00 [pubmed] PHST- 2021/02/09 06:00 [medline] PHST- 2019/12/25 06:00 [entrez] AID - S0196-9781(19)30209-8 [pii] AID - 10.1016/j.peptides.2019.170231 [doi] PST - ppublish SO - Peptides. 2020 Mar;125:170231. doi: 10.1016/j.peptides.2019.170231. Epub 2019 Dec 20.