Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues

Kulve, Jennifer S. ten; Veltman, Dick J.; Gerdes, Victor E. A.; Bloemendaal, Liselotte van; Barkhof, Frederik; Deacon, Carolyn F.; Holst, Jens J.; Drent, Madeleine L.; Diamant, Michaëla; IJzerman, Richard G.

doi:10.2337/dc16-2113

Cited by 52 publications

(74 citation statements)

References 39 publications

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“…By contrast, the insulinotropic effect of GLP-1 is better maintained in T2DM (5). Moreover, GLP-1 has a physiological role in slowing gastric emptying (6) and suppressing glucagon secretion (7) and energy intake (8). Accordingly, GLP-1 is more important than GIP in driving the incretin effect and GIGD in T2DM.…”

mentioning

confidence: 99%

Comparative Effects of Proximal and Distal Small Intestinal Glucose Exposure on Glycemia, Incretin Hormone Secretion, and the Incretin Effect in Health and Type 2 Diabetes

et al. 2019

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Cells releasing glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide 1 (GLP-1) are distributed predominately in the proximal and distal gut, respectively. Hence, the region of gut exposed to nutrients may influence GIP and GLP-1 secretion and impact on the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). We evaluated glycemic and incretin responses to glucose administered into the proximal or distal small intestine and quantified the corresponding incretin effect and GIGD in health and type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS Ten healthy subjects and 10 patients with T2DM were each studied on four occasions. On two days, a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus, and 30 g glucose with 3 g 3-Omethylglucose (a marker of glucose absorption) was infused into either site and 0.9% saline into the alternate site over 60 min. Matching intravenous isoglycemic clamp studies were performed on the other two days. Blood glucose, serum 3-Omethylglucose, and plasma hormones were evaluated over 180 min. RESULTS In both groups, blood glucose and serum 3-O-methylglucose concentrations were higher after proximal than distal glucose infusion (all P < 0.001). Plasma GLP-1 increased minimally after proximal, but substantially after distal, glucose infusion, whereas GIP increased promptly after both infusions, with concentrations initially greater, but less sustained, with proximal versus distal infusion (all P < 0.001). Both the incretin effect and GIGD were less with proximal than distal glucose infusion (both P £ 0.009). CONCLUSIONS The distal, as opposed to proximal, small intestine is superior in modulating postprandial glucose metabolism in both health and T2DM.

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confidence: 99%

Comparative Effects of Proximal and Distal Small Intestinal Glucose Exposure on Glycemia, Incretin Hormone Secretion, and the Incretin Effect in Health and Type 2 Diabetes

et al. 2019

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“…Appetite ratings were minimally affected in response to intraduodenal fat infusion, with and without vildagliptin or exendin (9–39), despite differences in GLP‐1 signalling. Previous studies have shown that DPP‐4 inhibition and antagonism of GLP‐1 receptors are also associated with changes in plasma levels of PYY that tend to confound the effect of GLP‐1 on appetite and energy intake . Moreover, the participants with T2DM in the present study had a mean age of ~69 years, so that their appetite sensations are expected to be decreased …”

Section: Discussionmentioning

confidence: 83%

“…Previous studies have shown that DPP-4 inhibition and antagonism of GLP-1 receptors are also associated with changes in plasma levels of PYY that tend to confound the effect of GLP-1 on appetite and energy intake. 44,45 Moreover, the participants with T2DM in the present study had a mean age of~69 years, so that their appetite sensations are expected to be decreased. 46 Several limitations should be noted in interpreting our findings.…”

Section: Discussionmentioning

confidence: 91%

Role of endogenous glucagon‐like peptide‐1 enhanced by vildagliptin in the glycaemic and energy expenditure responses to intraduodenal fat infusion in type 2 diabetes

Xie

Wang

Jones

et al. 2019

Diabetes Obesity Metabolism

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Aim To evaluate the effects of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor vildagliptin on glycaemic and energy expenditure responses during intraduodenal fat infusion, as well as the contribution of endogenous glucagon‐like peptide‐1 (GLP‐1) signalling, in people with type 2 diabetes (T2DM). Methods A total of 15 people with T2DM managed by diet and/or metformin (glycated haemoglobin 49.3 ± 2.1 mmol/mol) were studied on three occasions (two with vildagliptin and one with placebo) in a double‐blind, randomized, crossover fashion. On each day, vildagliptin 50 mg or placebo was given orally, followed by intravenous exendin (9–39) 600 pmol/kg/min, on one of the two vildagliptin treatment days, or 0.9% saline over 180 minutes. At between 0 and 120 minutes, a fat emulsion was infused intraduodenally at 2 kcal/min. Energy expenditure, plasma glucose and glucose‐regulatory hormones were evaluated. Results Intraduodenal fat increased plasma GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP), insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P < 0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP‐1 was higher (all P < 0.05), and energy expenditure tended to be lower after vildagliptin (P = 0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP‐1 (both total and intact), and energy expenditure were higher during intravenous exendin (9–39) than saline (all P < 0.05). Conclusions In well‐controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP‐1.

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“…The central nervous system, especially the hypothalamus, can control the central and peripheral energy homeostasis through neuropeptides and neurotransmitters [59]. Some studies have confirmed that changes in the nervous system can be significantly observed after RYGB [60][61][62]. Liver fat metabolism is regulated by not only humoral but also the nervous system.…”

Section: Discussionmentioning

confidence: 99%

Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway

Tang

et al. 2020

Journal of Diabetes Research

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Purpose. To investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on markers of liver mitochondrial dynamics and find new therapeutic basis on obese type 2 diabetes mellitus (T2DM) patients. Materials and Methods. Thirty-two rats were divided into nondiabetic group, diabetic group, sham group, and RYGB group. The Dual-energy X-ray absorptiometry (DEXA) was used to detect short-term curriculum vitae for rat body component and fat and lean mass. Hepatic lipid content and triglyceride levels were detected by Oil Red O staining. Western blotting was used to examine autophagy and mammalian target of rapamycin/P70S6 kinase (mTOR/p70S6K) pathway-related proteins. The carbon dioxide production from the oxidation of [14C] oleate was measured. Plasma glucose was measured by glucose oxidase assay. The insulin and C-peptide were detected. Triacylglyceride (TG) and free fat acid (FFA) in plasma were determined by enzymatic colorimetric assays. Results. RYGB improved metabolic parameters and enhanced plasma GLP-1 level, ameliorated the lipopexia, and increased insulin sensitivity in the liver; RYGB promoted the hepatic autophagy and inhibited the mTOR/p70S6K signaling pathway. GLP-1 reduced fat load and increased fatty acid β-oxidation by activated autophagy to regulate the hepatic lipid pathway through mTOR/p70S6K signaling pathway. Conclusions. RYGB may reduce liver lipid toxicity and improve insulin sensitivity through activating the hepatic fat hydrolysis pathway and inhibiting the liver fat synthesis pathway. However, the transport pathway of liver fat does not play a key role.

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Elevated Postoperative Endogenous GLP-1 Levels Mediate Effects of Roux-en-Y Gastric Bypass on Neural Responsivity to Food Cues

Cited by 52 publications

References 39 publications

Comparative Effects of Proximal and Distal Small Intestinal Glucose Exposure on Glycemia, Incretin Hormone Secretion, and the Incretin Effect in Health and Type 2 Diabetes

Comparative Effects of Proximal and Distal Small Intestinal Glucose Exposure on Glycemia, Incretin Hormone Secretion, and the Incretin Effect in Health and Type 2 Diabetes

Role of endogenous glucagon‐like peptide‐1 enhanced by vildagliptin in the glycaemic and energy expenditure responses to intraduodenal fat infusion in type 2 diabetes

Roux-en-Y Gastric Bypass in Obese Diabetic Rats Promotes Autophagy to Improve Lipid Metabolism through mTOR/p70S6K Signaling Pathway

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