Augmented GLP-1 Secretion as Seen After Gastric Bypass May Be Obtained by Delaying Carbohydrate Digestion

Martinussen, Christoffer; Bojsen‐Møller, Kirstine N.; Dirksen, Carsten; Svane, Maria S.; Kristiansen, Viggo B.; Hartmann, Bolette; Holst, Jens J.; Madsbad, Sten

doi:10.1210/jc.2018-02661

Cited by 19 publications

(23 citation statements)

References 63 publications

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“…At baseline in a fasting state, we were not able to determine changes in circulating levels of GLP-1. However, GLP-1 secretion was reported to be dependent on the rate of carbohydrate digestion [41] which could explain the lack of GLP-1 change in our cohort as blood samples were taken in an overnight fasting state.…”

Section: Discussionmentioning

confidence: 77%

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

et al. 2019

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Background Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. Aim To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. Methods We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, Cpeptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. Results After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). Conclusion Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.

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Section: Discussionmentioning

confidence: 77%

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

et al. 2019

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“…Enhanced gut hormone secretion after RYGB is likely multifactorial, with other possible mechanisms including changes in intestinal nutrient-sensing capacity caused by delayed carbohydrate digestion or increased plasma bile acids. 12,13 The rise in peak postprandial glucose and insulin we found with orlistat is likely explained by prior studies showing that orlistat treatment increases gastric emptying. 8 Increased gastric emptying elevates postprandial glucose concentrations, 14 and elevated blood glucose and insulin responses following orlistat administration have been previously described.…”

Section: Discussionmentioning

confidence: 80%

“…Intraduodenal lipid infusion has been shown to allow for generation of fatty acids that, in turn, stimulate L‐cells to secrete GLP‐1 or PYY, a pathway which is blocked when orlistat is given with a meal. Enhanced gut hormone secretion after RYGB is likely multifactorial, with other possible mechanisms including changes in intestinal nutrient‐sensing capacity caused by delayed carbohydrate digestion or increased plasma bile acids 12,13 …”

Section: Discussionmentioning

confidence: 99%

Short‐term intestinal lipase inhibition in normal‐weight individuals does not affect postprandial peptide YY_3‐36 and glucagon‐like peptide‐1 levels, hunger or satiety

Nguyen

Kolobova

Wolfe

et al. 2020

Diabetes Obesity Metabolism

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Fat malabsorption associated with Roux-en-Y gastric bypass (RYGB) may contribute to elevated postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after the procedure, leading to sustained weight loss and appetite reduction. This study investigated whether fat malabsorption via orlistat increases GLP-1 and PYY and if these increases would be proportional to changes in hunger and satiety. Five healthy participants received standardized meals with 120 mg orlistat or placebo in a randomized, double-blinded, crossover design for 3 days. On the final day, glucose, insulin, GLP-1, PYY 3-36 and visual analogue scores for hunger and satiety were measured over a 14-hour period that included three meals. Fasting, 14-hour area under the curve (AUC) and meal-related AUC for glucose and insulin were similar, although postprandial increases in peak insulin and glucose were greater with orlistat. PYY 3-36 , GLP-1, hunger and satiety were not different. In conclusion, short-term orlistat administration does not enhance postprandial GLP-1 or PYY 3-36 or affect hunger or satiety in normal-weight individuals. Furthermore, fat malabsorption from RYGB is unlikely to mediate subsequent postprandial increases in GLP-1 and PYY.

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“…If similar effects could be obtained nonsurgically by pharmacological or nutritional enhancement of GLP-1 secretion, it would have important implications for the treatment of diabetes and obesity. The greater GLP-1 responses likely result from the surgical rerouting of nutrients to the distal small intestine with a higher density of L cells (8,29). The other major incretin hormone, glucosedependent insulinotropic polypeptide (GIP), originates from the more proximally located K cells.…”

Section: Introductionmentioning

confidence: 99%

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

Martinussen

Veedfald

Dirksen

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weight-loss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. In vitro, incretin release depends on glucose absorption via sodium-glucose cotransporter 1 (SGLT1). We investigated the importance of SGLT1/SGLT2 for enteropancreatic hormone concentrations and glucose metabolism after RYGB in a randomized, controlled, crossover study. Ten RYGB-operated patients ingested 50 g of oral glucose with and without acute pretreatment with 600 mg of the SGLT1/SGLT2-inhibitor canagliflozin. Paracetamol and 3- O-methyl-d-glucopyranose (3-OMG) were added to the glucose drink to evaluate rates of intestinal entry and absorption of glucose, respectively. Blood samples were collected for 4 h. The primary outcome was 4-h plasma GLP-1 (incremental area-under the curve, iAUC). Secondary outcomes included glucose, GIP, insulin, and glucagon. Canagliflozin delayed glucose absorption (time-to-peak 3-OMG: 50 vs. 132 min, P < 0.01) but did not reduce iAUC GLP-1 (6,067 vs. 7,273·min·pmol−1·L−1, P = 0.23), although peak GLP-1 concentrations were lowered (−28%, P = 0.03). Canagliflozin reduced GIP (iAUC −28%, P = 0.01; peak concentrations −57%, P < 0.01), insulin, and glucose excursions, whereas plasma glucagon (AUC 3,216 vs. 4,160 min·pmol·L−1, P = 0.02) and amino acids were increased. In conclusion, acute SGLT1/SGLT2-inhibition during glucose ingestion did not reduce 4-h plasma GLP-1 responses in RYGB-patients but attenuated the early rise in GLP-1, GIP, and insulin, whereas late glucagon concentrations were increased. The results suggest that SGLT1-mediated glucose absorption contributes to incretin hormone secretion after RYGB.

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Augmented GLP-1 Secretion as Seen After Gastric Bypass May Be Obtained by Delaying Carbohydrate Digestion

Cited by 19 publications

References 63 publications

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Short‐term intestinal lipase inhibition in normal‐weight individuals does not affect postprandial peptide YY_3‐36 and glucagon‐like peptide‐1 levels, hunger or satiety

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

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Augmented GLP-1 Secretion as Seen After Gastric Bypass May Be Obtained by Delaying Carbohydrate Digestion

Cited by 19 publications

References 63 publications

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients

Short‐term intestinal lipase inhibition in normal‐weight individuals does not affect postprandial peptide YY3‐36 and glucagon‐like peptide‐1 levels, hunger or satiety

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery

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Short‐term intestinal lipase inhibition in normal‐weight individuals does not affect postprandial peptide YY_3‐36 and glucagon‐like peptide‐1 levels, hunger or satiety