Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

Objective: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Research Design and Methods: Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. Results: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose. Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Conclusion: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

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Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

10.2337/figshare.16989505.v1 ◽

2021 ◽

Author(s):

Malini Prasad ◽

Victoria Mark ◽

Chanel Ligon ◽

Roxanne Dutia ◽

Nandini Nair ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Cell Function ◽

Diabetes Remission ◽

Oral Glucose ◽

Β Cell ◽

Remission Status ◽

Β Cell Function

Objective: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Research Design and Methods: Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. Results: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose. Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Conclusion: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

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The Role of β-Cell Function and Insulin Sensitivity in the Remission of Type 2 Diabetes after Gastric Bypass Surgery

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2011-0446 ◽

2011 ◽

Vol 96 (9) ◽

pp. E1372-E1379 ◽

Cited By ~ 125

Author(s):

M. Nannipieri ◽

A. Mari ◽

M. Anselmino ◽

S. Baldi ◽

E. Barsotti ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Bypass Surgery ◽

Cell Function ◽

Gastric Bypass Surgery ◽

Β Cell ◽

Β Cell Function

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Gastrointestinal hormones and β-cell function after gastric bypass and sleeve gastrectomy: an RCT (Oseberg)

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab643 ◽

2021 ◽

Author(s):

Farhat Fatima ◽

Jøran Hjelmesæth ◽

Kåre Inge Birkeland ◽

Gulseth Løvdal Hanne ◽

Jens Kristoffer Hertel ◽

...

Keyword(s):

Type 2 Diabetes ◽

Gastric Bypass ◽

Sleeve Gastrectomy ◽

Cell Function ◽

Gastrointestinal Hormones ◽

Diabetes Remission ◽

Β Cell ◽

Post Surgery ◽

Β Cell Function

Abstract Context Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and β-cell function in type 2 diabetes remains unclear. Objective To compare gastrointestinal hormones and β-cell function assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery hypothesizing higher GLP-1 levels and greater β-cell response to glucose after RYGB than after SG. Design, Setting, Patients, and Interventions Randomized, triple blind, single-center trial at a tertiary care center in Norway. Primary outcomes; diabetes remission and IVGTT derived β-cell function. Participants with obesity and type 2 diabetes allocated (1:1) to RYGB or SG. Main outcome measures Gastrointestinal hormone profiles and insulin secretion [β-cell glucose sensitivity (β-GS)] derived from 180 minutes OGTTs. Results 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1-year were higher after RYGB than after SG, 77% versus 48%, p = 0.002. Incremental area under the curve (iAUC0-180) glucagon-like peptide-1 (GLP-1) and β-GS increased more after RYGB than after SG, 1-year between-group difference 1173 pmol/l*min (95% CI 569 to 1776), p = 0.0010, and 0.45 pmol/kg/min/mmol (95% CI 0.15 to 0.75), p = 0.0032, respectively. Post-surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher β-GS and higher GLP-1 secretion. Conclusions RYGB was associated with greater improvement in β-cell function and higher postprandial GLP-1 levels than SG.

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Faculty Opinions recommendation of Gastric bypass and banding equally improve insulin sensitivity and β cell function.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718381945.793494982 ◽

2014 ◽

Author(s):

Naveed Sattar

Keyword(s):

Gastric Bypass ◽

Insulin Sensitivity ◽

Cell Function ◽

Improve Insulin Sensitivity ◽

Β Cell ◽

Β Cell Function

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The role of gut microbiota and amino metabolism in the effects of improvement of islet β-cell function after modified jejunoileal bypass

Scientific Reports ◽

10.1038/s41598-021-84355-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cai Tan ◽

Zhihua Zheng ◽

Xiaogang Wan ◽

Jiaqing Cao ◽

Ran Wei ◽

...

Keyword(s):

Gut Microbiota ◽

Cell Function ◽

Body Weight Gain ◽

Fasting Blood Glucose ◽

Jejunoileal Bypass ◽

Β Cell ◽

Β Cell Function ◽

Branched Chain

AbstractThe change in gut microbiota is an important mechanism of the amelioration of type 2 diabetes mellitus (T2DM) after bariatric surgery. Here, we observe that the modified jejunoileal bypass effectively decreases body weight gain, fasting blood glucose, and lipids level in serum; additionally, islet β-cell function, glucose tolerance, and insulin resistance were markedly ameliorated. The hypoglycemic effect and the improvement in islet β-cell function depend on the changes in gut microbiota structure. modified jejunoileal bypass increases the abundance of gut Escherichia coli and Ruminococcus gnavus and the levels of serum glycine, histidine, and glutamine in T2DM rats; and decreases the abundance of Prevotella copri and the levels of serum branched chain amino acids, which are significantly related to the improvement of islet β-cell function in T2DM rats. Our results suggest that amino acid metabolism may contribute to the islet β-cell function in T2DM rats after modified jejunoileal bypass and that improving gut microbiota composition is a potential therapeutic strategy for T2DM.

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Role of Sex Steroids in β Cell Function, Growth, and Survival

Trends in Endocrinology and Metabolism ◽

10.1016/j.tem.2016.08.008 ◽

2016 ◽

Vol 27 (12) ◽

pp. 844-855 ◽

Cited By ~ 39

Author(s):

Franck Mauvais-Jarvis

Keyword(s):

Sex Steroids ◽

Cell Function ◽

Β Cell ◽

Growth And Survival ◽

Β Cell Function

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Functional Role of Serotonin in Insulin Secretion in a Diet-Induced Insulin-Resistant State

Endocrinology ◽

10.1210/en.2014-1687 ◽

2014 ◽

Vol 156 (2) ◽

pp. 444-452 ◽

Cited By ~ 55

Author(s):

Kyuho Kim ◽

Chang-Myung Oh ◽

Mica Ohara-Imaizumi ◽

Sangkyu Park ◽

Jun Namkung ◽

...

Keyword(s):

Insulin Secretion ◽

Pancreatic Islets ◽

Cell Function ◽

Β Cell ◽

Pancreas Perfusion ◽

Insulin Resistant ◽

Β Cell Function ◽

Resistant State ◽

Insulin Resistant State

The physiological role of serotonin, or 5-hydroxytryptamine (5-HT), in pancreatic β-cell function was previously elucidated using a pregnant mouse model. During pregnancy, 5-HT increases β-cell proliferation and glucose-stimulated insulin secretion (GSIS) through the Gαq-coupled 5-HT2b receptor (Htr2b) and the 5-HT3 receptor (Htr3), a ligand-gated cation channel, respectively. However, the role of 5-HT in β-cell function in an insulin-resistant state has yet to be elucidated. Here, we characterized the metabolic phenotypes of β-cell-specific Htr2b−/− (Htr2b βKO), Htr3a−/− (Htr3a knock-out [KO]), and β-cell-specific tryptophan hydroxylase 1 (Tph1)−/− (Tph1 βKO) mice on a high-fat diet (HFD). Htr2b βKO, Htr3a KO, and Tph1 βKO mice exhibited normal glucose tolerance on a standard chow diet. After 6 weeks on an HFD, beginning at 4 weeks of age, both Htr3a KO and Tph1 βKO mice developed glucose intolerance, but Htr2b βKO mice remained normoglycemic. Pancreas perfusion assays revealed defective first-phase insulin secretion in Htr3a KO mice. GSIS was impaired in islets isolated from HFD-fed Htr3a KO and Tph1 βKO mice, and 5-HT treatment improved insulin secretion from Tph1 βKO islets but not from Htr3a KO islets. Tph1 and Htr3a gene expression in pancreatic islets was not affected by an HFD, and immunostaining could not detect 5-HT in pancreatic islets from mice fed an HFD. Taken together, these results demonstrate that basal 5-HT levels in β-cells play a role in GSIS through Htr3, which becomes more evident in a diet-induced insulin-resistant state.

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