Gastric Inhibitory Polypeptide and Insulin Release in Response to Oral and Intravenous Glucose in Coeliac Disease

Lauritsen, K. B.; Lauritzen, Jes Bruun; Christensen, K. C.

doi:10.3109/00365528209182046

Cited by 14 publications

(8 citation statements)

References 10 publications

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“…Immunoneutralization experiments showed that intestinal extracts contain potent insulinotropic agents in addition to GIP [28]. Furthermore, investigations by a study in patients with resections of different parts of the small intestine, as well as in patients with celiac disease, showed that the incretin effect does not correlate to the secretion of GIP, and that the distal small intestine releases an additional incretin hormone [29,30].…”

Section: Glucose-dependent Insulinotropic Polypeptide (Gip)mentioning

confidence: 99%

Incretins, insulin secretion and Type 2 diabetes mellitus

2004

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When glucose is taken orally, insulin secretion is stimulated much more than it is when glucose is infused intravenously so as to result in similar glucose concentrations. This effect, which is called the incretin effect and is estimated to be responsible for 50 to 70% of the insulin response to glucose, is caused mainly by the two intestinal insulin-stimulating hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Their contributions have been confirmed in mimicry experiments, in experiments with antagonists of their actions, and in experiments where the genes encoding their receptors have been deleted. In patients with Type 2 diabetes, the incretin effect is either greatly impaired or absent, and it is assumed that this could contribute to the inability of these patients to adjust their insulin secretion to their needs. In studies of the mechanism of the impaired incretin effect in Type 2 diabetic patients, it has been found that the secretion of GIP is generally normal, whereas the secretion of GLP-1 is reduced, presumably as a consequence of the diabetic state. It might be of even greater importance that the effect of GLP-1 is preserved whereas the effect of GIP is severely impaired. The impaired GIP effect seems to have a genetic background, but could be aggravated by the diabetic state. The preserved effect of GLP-1 has inspired attempts to treat Type 2 diabetes with GLP-1 or analogues thereof, and intravenous GLP-1 administration has been shown to be able to near-normalize both fasting and postprandial glycaemic concentrations in the patients, perhaps because the treatment compensates for both the impaired secretion of GLP-1 and the impaired action of GIP. Several GLP-1 analogues are currently in clinical development and the reported results are, so far, encouraging. The incretin effectThe incretin effect seems to play a major role in the regulation of glucose metabolism in healthy subjects. "The incretin effect" implies that ingestion of carbohydrates (glucose) causes the release from the intestinal mucosa of substances that enhance insulin secretion beyond the release caused by the absorbed glucose itself [1]. The effect can be quantified by comparing insulin or C-peptide responses to oral or intravenous glucose loads, adjusted to cause identical increases of plasma glucose concentrations. The much higher responses observed after oral administration

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Section: Glucose-dependent Insulinotropic Polypeptide (Gip)mentioning

confidence: 99%

Incretins, insulin secretion and Type 2 diabetes mellitus

2004

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“…These correlations were not detected in the control non-CD population, which suggests possible dysregulation of glucose metabolism, as has been suggested in CD. [3][4][5]11,[17][18][19][20][21] Unfortunately, the data are not sufficient to imply any clinical relevance, but they do warrant further research. Previous studies have reported that multiple processes, such as N-glycosylation and receptor oligomerization, may regulate the exit of functional GLP1Rs from the endoplasmic reticulum and their maintenance in the plasma membrane.…”

Section: Discussionmentioning

confidence: 98%

“…These correlations were not detected in the control non-CD population, which suggests possible dysregulation of glucose metabolism, as has been suggested in CD. 3–5,11,17–21…”

Section: Discussionmentioning

confidence: 99%

“…The hypothesis that variations in gut-hormone profiles may influence, and be influenced by the pathophysiology of digestive diseases such as CD is based on several parameters: (1) the location of the L cells, and their probable damage due to mucosal atrophy; and (2) published, albeit inconsistent data regarding serum levels of glucose-dependent insulinotropic peptide (GIP), enteroglucagon, oxyntomodulin-like, GLP-1 and GLP-2 from studies performed mostly in adults, 3,4,11,[17][18][19][20] with only two of them addressing the pediatric population with and without CD. 5,21 GLP-1 is released in response to glucose load and stimulates insulin secretion.…”

Section: Discussionmentioning

confidence: 99%

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Simultaneous analyses of carbohydrate-mediated serum GLP-1 and GLP-2 and duodenal receptor expression in children with and without celiac disease

Rachmiel

Ben-Yehudah

Shirin

et al. 2019

Therap Adv Gastroenterol

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Background: Variability in glucagon-like peptide (GLP)-1 and GLP-2 plasma concentrations has been suggested in Celiac disease (CD), with inconclusive results. We assessed the association between serum levels of GLP-1 and GLP-2 and their duodenal receptor expression in children with and without CD. Methods: This was a two-part, cross-sectional and prospective cohort study. Group assignment, performed after duodenal samples for mRNA expression of GLP-1 receptor (GLP1R) and GLP-2 receptor (GLP2R) , were taken during esophagogastroduodenoscopy. The control group consisted of patients with normal endoscopy and negative serology. The CD group consisted of patients with positive serology and endoscopy suggestive of CD. All had an oral glucose-tolerance test (OGTT). CD patients underwent a second OGTT after 6 months of a gluten-free diet (GFD). Results: The CD group included 12 patients; 7 males with mean age 9.2 ± 2.5 years. The control group included 10 patients; 5 males with mean age 12 ± 4 years, ( p = 0.14). No differences were detected in basal or peak levels of GLP-1 or GLP-2 between control, naïve CD (before GFD) and treated CD (after GFD) groups. Expression of GLP1R and GLP2R mRNA was similar. Significant positive correlations between glucose and C-peptide secretion ( r = 0.9, p < 0.01) and GLP-1 and GLP-2 ( r = 0.8, p = 0.01) were detected in the control group. Significant negative correlations were found in the naïve CD group between GLP2R expression and glucose secretion ( r = −0.68, p = 0.015) and GLP1R expression and serum GLP-1 ( r = −0.7, p = 0.016). Conclusions: Although no significant differences were detected in secretion patterns or gut receptor expression of GLP-1 and GLP-2 in healthy versus CD pediatric patients, the detected discrepancy between the ligand levels and their tissue receptors requires additional study.

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“…Immunoneutralization experiments clearly showed that intestinal extracts contain potent insulinotropic agents in addition to GIP (27). Also, investigations by Lauritsen and colleagues (28,29) in patients with resections of different parts of the small intestine, or in celiac disease, showed that the incretin effect does not correlate to GIP secretion, and that the distal small intestine releases an additional incretin. In all probability, this additional incretin is GLP-1.…”

Section: The Incretin Hormonesmentioning

confidence: 98%

The Incretin Approach for Diabetes Treatment

Holst

Ørskov

2004

Diabetes

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Glucagon-like peptide (GLP)-1 is a gut hormone that stimulates insulin secretion, gene expression, and ␤-cell growth. Together with the related hormone glucosedependent insulinotropic polypeptide (GIP), it is responsible for the incretin effect, the augmentation of insulin secretion after oral as opposed to intravenous administration of glucose. Type 2 diabetic patients typically have little or no incretin-mediated augmentation of insulin secretion. This is due to decreased secretion of GLP-1 and loss of the insulinotropic effects of GIP. GLP-1, however, retains insulinotropic effects, and the hormone effectively improves metabolism in patients with type 2 diabetes. Continuous subcutaneous administration greatly improved glucose profiles and lowered body weight and HbA 1c levels. Further, free fatty acid levels were lowered, insulin resistance was improved, and ␤-cell performance was greatly improved.

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Gastric Inhibitory Polypeptide and Insulin Release in Response to Oral and Intravenous Glucose in Coeliac Disease

Cited by 14 publications

References 10 publications

Incretins, insulin secretion and Type 2 diabetes mellitus

Incretins, insulin secretion and Type 2 diabetes mellitus

Simultaneous analyses of carbohydrate-mediated serum GLP-1 and GLP-2 and duodenal receptor expression in children with and without celiac disease

The Incretin Approach for Diabetes Treatment

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