Four weeks of near‐normalization of blood glucose has no effect on postprandial GLP‐1 and GIP secretion, but augments pancreatic B‐cell responsiveness to a meal in patients with Type 2 diabetes

Højberg, Patricia V.; Vilsbøll, Tina; Zander, Mette; Knop, Filip K.; Krarup, Thure; Vølund, Anders; Holst, Jens J.; Madsbad, Sten

doi:10.1111/j.1464-5491.2008.02579.x

Cited by 52 publications

(37 citation statements)

References 37 publications

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“…GLP-1 responses to mixed-meal tests have consistently been shown to be attenuated in patients with type 2 diabetes (6,7), and recently this has been confirmed in another study from our group (8). In the study in question, we do not find compromised GLP-1 responses during OGTT in our patients with type 2 diabetes.…”

supporting

confidence: 84%

Response to Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951–1959

et al. 2008

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supporting

confidence: 84%

Response to Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951–1959

et al. 2008

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“…Accordingly, Asmar et al (1) reported no further effect on insulin secretion when additional GIP was infused during a meal that by itself caused a large endogenous GIP response. However, the peaks of total and intact GIP in the present study amounted to only about one-third of the responses during meal tests with DPP-4 inhibition in nonoperated individuals, which raises the possibility that an attenuated GIP response after RYGB surgery explains the present findings (17,59). Nevertheless it was unexpected that more than twofold increased levels of active GIP could not compensate for the absence of activation of GLP-1R pathways, particularly given our previous demonstration of a preserved insulinotropic action of GIP after RYGB (8).…”

Section: E510contrasting

confidence: 49%

Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery

Svane

Bojsen‐Møller

Nielsen

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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-Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and ␤-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9 -39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated ␤-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two-to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or ␤-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB.Roux-en-Y gastric bypass; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; exendin-(9 -39); dipeptidyl peptidase-4 inhibition ROUX-EN-Y GASTRIC BYPASS (RYGB) is an effective treatment of severe obesity and induces large and sustainable weight loss, which is superior to diet, intensive lifestyle, or pharmaceutical interventions (47, 51). Moreover, RYGB improves glycemic control within days after surgery, before major weight loss (24), and induces remission of type 2 diabetes in the majority of patients (5, 47). Patients with preoperative normal glucose tolerance (NGT) also display changed postprandial glycemic profile after RYGB with increased peak plasma glucose, followed by a lower nadir (24,45). A combination of improved hepatic insulin sensitivity induced by hypocaloric postoperative diet (18), rapid glucose absorption (19), and exaggerated postprandial insulin secretion seems to be responsible for the early changes in glucose metabolism after RYGB in patients with NGT and type 2 diabetes (3).The postprandial gastrointestinally induced stimulation of insulin secretion, the incretin effect, is due to the insulinotropic effects of the two hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) (38,56). In glucose-tolerant subjects, GLP-1 and GIP contribute nearly equally to the incretin effect, which explains up to 70% of the postprandial insulin secretion (36,38,56). The incretin effect is severely impaired in type 2 diabetes (35) but is also reduced in obese people with NGT ...

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“…In accordance, it is believed that afferent neurons in the intestinal mucosa mediate the major glucoselowering effect of GLP1 (5). The predominant, but not unchallenged, view on GLP1 secretion in patients with type 2 diabetes (T2DM) is that some, but not all, patients (6) have defective postprandial responses (7,8,9,10), whereas levels during oral glucose tolerance tests (OGTTs) usually are comparable to controls (11,12,13,14,15,16). As bile acids may influence nutrient-induced GLP1 secretion from the L cells (via TGR5), postprandial flow of bile from the gallbladder into the intestine may potentiate the postprandial L cell response.…”

Section: Introductionmentioning

confidence: 83%

Postprandial gallbladder emptying in patients with type 2 diabetes: potential implications for bile-induced secretion of glucagon-like peptide 1

Sonne

Rehfeld

Holst

et al. 2014

European Journal of Endocrinology

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Objective: Recent preclinical work has suggested that postprandial flow of bile acids into the small intestine potentiates nutrient-induced glucagon-like peptide 1 (GLP1) secretion via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells. The notion of bile-induced GLP1 secretion combined with the findings of reduced postprandial gallbladder emptying in patients with type 2 diabetes (T2DM) led us to speculate whether reduced postprandial GLP1 responses in some patients with T2DM arise as a consequence of diabetic gallbladder dysmotility. Design and methods: In a randomised design, 15 patients with long-standing T2DM and 15 healthy age-, gender-and BMI-matched control subjects were studied during 75-g oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals: i) 2.5 g fat, 107 g carbohydrate and 13 g protein; ii) 10 g fat, 93 g carbohydrate and 11 g protein; and iii) 40 g fat, 32 g carbohydrate and 3 g protein. Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP1, glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin and gastrin were measured. Furthermore, gallbladder emptying and gastric emptying were examined. Results: Gallbladder emptying increased with increasing meal fat content, but no intergroup differences were demonstrated. GIP and GLP1 responses were comparable among the groups with GIP levels being higher following high-fat meals, whereas GLP1 secretion was similar after both OGTT and meals. Conclusions: In conclusion, patients with T2DM exhibited normal gallbladder emptying to meals with a wide range of fat content. Incretin responses were similar to that in controls, and an association with postprandial gallbladder contraction could not be demonstrated.

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Four weeks of near‐normalization of blood glucose has no effect on postprandial GLP‐1 and GIP secretion, but augments pancreatic B‐cell responsiveness to a meal in patients with Type 2 diabetes

Abstract: Four weeks of near-normalization of BG had no effect on postprandial secretion of incretin hormones. Nevertheless, several parameters of meal-induced insulin secretion improved after insulin treatment.

Cited by 52 publications

References 37 publications

Response to Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951–1959

Response to Comment on: Knop et al. (2007) Reduced Incretin Effect in Type 2 Diabetes: Cause or Consequence of the Diabetic State? Diabetes 56:1951–1959

Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery

Postprandial gallbladder emptying in patients with type 2 diabetes: potential implications for bile-induced secretion of glucagon-like peptide 1

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