GLP-1 Response to a Mixed Meal: What Happens 10 Years after Roux-en-Y Gastric Bypass (RYGB)?

Dar, M. Saeed; Chapman, William H.; Pender, John R.; Drake, Almond J.; O’Brien, Kevin F.; Tanenberg, Robert J.; Dohm, G. Lynis; Pories, Walter J.

doi:10.1007/s11695-012-0624-1

Cited by 89 publications

(58 citation statements)

References 21 publications

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“…GLP-1 secretion has been demonstrated to increase after RYGB in obese patients to a supraphysiological level, but GLP-1 secretion after RYGB has not yet been evaluated in lean patients. We aimed to reproduce the physiological changes observed in obese humans following gastric bypass surgery in lean minipigs, especially the postprandial increase in GLP-1 secretion [6,13,14,15]. The main difficulty was to determine the optimal surgical technique, taking into account the anatomical discrepancies between humans and minipigs.…”

Section: Discussionmentioning

confidence: 99%

Gastric Bypass Increases Postprandial Insulin and GLP-1 in Nonobese Minipigs

et al. 2014

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Background: Gastric bypass in obese patients induces a dramatic increase of postprandial insulin and glucagon-like peptide-1 (GLP-1) secretion, independently of weight loss. We explored postprandial insulin and GLP-1 secretion in nonobese minipigs before and after RYGB. Methods: Lean adult Göttingen minipigs (n = 7) were submitted to an open gastric bypass surgery mimicking the clinical procedure in humans (30-cm³ gastric pouch/150-cm alimentary limb/70-cm biliary limb). All animals were evaluated at baseline and then 10 and 30 days after surgery. At each time point, serum glucose, insulin, GLP-1 and D-xylose levels were measured 3 h after a standardized mixed meal. Results: Weight remained stable during follow-up. Insulin and GLP-1 responses to the test meal were dramatically and similarly increased at 10 days and 1 month after RYGB. Maximal postprandial insulin and GLP-1 levels were 16.3 ± 1.7 mIU/l and 71.7 ± 16.5 pmol/l at baseline, 111.5 ± 38.9 mIU/l and 320.8 ± 84.0 pmol/l at 10 days and 96.6 ± 10.4 mIU/l and 297.3 ± 79.1 pmol/l at 1 month, respectively. D-Xylose absorption remained unchanged before and after surgery. Conclusions: RYGB induced a dramatic increase of postprandial insulin and GLP-1 secretion in nonobese minipigs. This preclinical model could help to understand the underlying metabolic effects of RYGB, focusing on the role of postsurgical anatomical rearrangement, especially duodenojejunal exclusion and ileal brake. This study supports the use of RYGB in diabetic nonobese patients in absence of obesity.

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Section: Discussionmentioning

confidence: 99%

Gastric Bypass Increases Postprandial Insulin and GLP-1 in Nonobese Minipigs

et al. 2014

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“…The enhanced gut hormone responses occur as early as one or two days after RYGBP independent of weight loss per se (67), thus implicating a process directly related to the procedure itself. The enhanced responses are evident even with caloric intake as small as 75 kcal, demonstrate a dose-dependent increment (68), and remain persistently elevated in the long-term postoperatively (69). In general, these altered PYY and GLP-1 responses are associated with reduced hunger and increased satiety (66).…”

Section: Mechanisms Underlying Effects Of Rygbpmentioning

confidence: 94%

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

Manning¹,

Pucci²,

Batterham³

2015

J. Clin. Invest.

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“…A major hypothesis is that changes in gut hormone release are crucial. Drastically increased postprandial circulating levels of GLP-1 and PYY have been demonstrated in clinical studies (18,32,33,36,38,44,47,50) and in rodent models (13, 16, 37, 56) for both Roux-en-Y gastric bypass and vertical sleeve gastrectomy.GLP-1 is a powerful hormone that acts both in the periphery and brain to stimulate insulin secretion, inhibit gastric emptying, and suppress food intake (for recent reviews, see Refs. 7,12,43).…”

mentioning

confidence: 94%

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

Zheng

Mumphrey

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

163

116

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-Exaggerated GLP-1 and PYY secretion is thought to be a major mechanism in the reduced food intake and body weight after Roux-en-Y gastric bypass surgery. Here, we use complementary pharmacological and genetic loss-of-function approaches to test the role of increased signaling by these gut hormones in high-fat diet-induced obese rodents. Chronic brain infusion of a supramaximal dose of the selective GLP-1 receptor antagonist exendin-9 -39 into the lateral cerebral ventricle significantly increased food intake and body weight in both RYGB and sham-operated rats, suggesting that, while contributing to the physiological control of food intake and body weight, central GLP-1 receptor signaling tone is not the critical mechanism uniquely responsible for the body weightlowering effects of RYGB. Central infusion of the selective Y2R-antagonist BIIE0246 had no effect in either group, suggesting that it is not critical for the effects of RYGB on body weight under the conditions tested. In a recently established mouse model of RYGB that closely mimics surgery and weight loss dynamics in humans, obese GLP-1R-deficient mice lost the same amount of body weight and fat mass and maintained similarly lower body weight compared with wild-type mice. Together, the results surprisingly provide no support for important individual roles of either gut hormone in the specific mechanisms by which RYGB rats settle at a lower body weight. It is likely that the beneficial effects of bariatric surgeries are expressed through complex mechanisms that require combination approaches for their identification.Roux-en-Y gastric bypass; gut hormones; brain; GLP-1R knockout; food intake; exendin-(9 -39), BIIE0246; high-fat diet THE NUMBER OF BARIATRIC SURGERIES performed has steadily increased because for many obese patients, it is the last hope for significant and enduring body weight loss and general improvement of health. There have been an increasing number of clinical and preclinical studies with the goal to unravel the mechanisms underlying these beneficial effects of bariatric surgeries, but there has not yet been a breakthrough. A major hypothesis is that changes in gut hormone release are crucial. Drastically increased postprandial circulating levels of GLP-1 and PYY have been demonstrated in clinical studies (18,32,33,36,38,44,47,50) and in rodent models (13, 16, 37, 56) for both Roux-en-Y gastric bypass and vertical sleeve gastrectomy.GLP-1 is a powerful hormone that acts both in the periphery and brain to stimulate insulin secretion, inhibit gastric emptying, and suppress food intake (for recent reviews, see Refs. 7,12,43). Exogenous administration of GLP-1 or its stable analog exendin-4, as well as PYY(3-36), has been shown in numerous preclinical and clinical studies to suppress food intake and lower body weight (e.g., (2,4,5,9,15,19,24,27,40,57,59) or to suppress hepatic glucose production (52), in some of them by directly acting on the brain. The stable GLP-1 receptor agonist exendin-4 is widely used by Type 2 diabetic patients to sta...

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GLP-1 Response to a Mixed Meal: What Happens 10 Years after Roux-en-Y Gastric Bypass (RYGB)?

Cited by 89 publications

References 21 publications

Gastric Bypass Increases Postprandial Insulin and GLP-1 in Nonobese Minipigs

Gastric Bypass Increases Postprandial Insulin and GLP-1 in Nonobese Minipigs

Roux-en-Y gastric bypass: effects on feeding behavior and underlying mechanisms

GLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents

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