Glucose-Dependent Insulinotropic Polypeptide (GIP)

Wolfe, M. Michael; Boylan, Michael O.; Kieffer, Timothy J.; Tseng, Chia-Yi

doi:10.1007/978-1-59259-695-9_18

Cited by 8 publications

(6 citation statements)

References 116 publications

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“…On the basis of the original definition, this would also imply inhibitory activities on gastric motility (11,31). However, the present data do not support a role for GIP in the regulation of gastric emptying in humans.…”

Section: Discussioncontrasting

confidence: 53%

“…Because GIP is released from endocrine cells in the intestinal mucosa in response to meal ingestion and acts to inhibit gastric acid secretion in animals as well as humans (3,15,27,32), it was proposed to be an enterogastrone (31,32). On the basis of the original definition, this would also imply inhibitory activities on gastric motility (11,31).…”

Section: Discussionmentioning

confidence: 99%

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Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

Meier

Goetze²,

Anstipp³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

128

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(GIP) has been demonstrated to inhibit gastric acid secretion and was proposed to possess "enterogastrone" activity. GIP effects on gastric emptying have not yet been studied. Fifteen healthy male volunteers (23.9 Ϯ 3.3 yr, body mass index 23.7 Ϯ 2.3 kg/m 2 ) were studied with the intravenous infusion of GIP (2 pmol⅐kg Ϫ1 ⅐min Ϫ1 ) or placebo, each administered to the volunteers on separate occasions from Ϫ30 to 360 min in the fasting state. At 0 min, a solid test meal (250 kcal containing [13 C]sodium octanoate) was served. Gastric emptying was calculated from the 13 CO2 exhalation rates in breath samples collected over 360 min. Venous blood was drawn in 30-min intervals for the determination of glucose, insulin, C-peptide, and GIP (total and intact). Statistical calculations were made by use of repeated-measures ANOVA and one-way ANOVA. During the infusion, GIP rose to steady-state concentrations of 159 Ϯ 15 pmol/l for total and 34 Ϯ 4 pmol/l for intact GIP (P Ͻ 0.0001). Meal ingestion further increased GIP concentrations in both groups, reaching peak levels of 265 Ϯ 20 and 82 Ϯ 9 pmol/l for total and 67 Ϯ 7 and 31 Ϯ 9 pmol/l for intact GIP during the administration of GIP and placebo, respectively (P Ͻ 0.0001). There were no differences in glucose, insulin, and C-peptide between the experiments with the infusion of GIP or placebo. Gastric half-emptying times were 120 Ϯ 9 and 120 Ϯ 18 min (P ϭ 1.0, with GIP and placebo, respectively). The time pattern of gastric emptying was similar in the two groups (P ϭ 0.98). Endogenous GIP secretion, as derived from the incremental area under the curve of plasma GIP concentrations in the placebo experiments, did not correlate to gastric half-emptying times (r 2 ϭ 0.15, P ϭ 0.15 for intact GIP; r 2 ϭ 0.21, P ϭ 0.086 for total GIP). We conclude that gastric emptying does not appear to be influenced by GIP. The secretion of GIP after meal ingestion is not suppressed by its exogenous administration. The lack of effect of GIP on gastric emptying underlines the differences between GIP and the second incretin glucagon-like peptide 1.glucose-dependent insulinotropic polypeptide; enterogastrone; incretin hormones GASTRIC INHIBITORY POLYPEPTIDE (GIP) is a 42-amino acid peptide secreted from K cells in the gut in response to nutrient ingestion (5,12). Early studies in dogs demonstrated an inhibition of gastric acid secretion during GIP administration (2, 3), leading to the assumption of GIP being an "enterogastrone." Later, inhibition of gastrin release by GIP was described as the mechanism underlying the reduction in gastric acid output (33). However, when more physiological doses of GIP were used, other investigators failed to demonstrate GIP effects on gastric acid secretion (34). Although the suppression of gastric acid secretion does not appear to be the major physiological role of GIP, glucose-dependent stimulation of insulin secretion was consistently observed in response to GIP administration under different experimental conditions (1, 7-10). Therefore, in 1976 Brown and Pe...

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Section: Discussioncontrasting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

Meier

Goetze²,

Anstipp³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

128

View full text Add to dashboard Cite

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“…Another possible explanation would be downregulation of the GIP receptor secondary to GIP hypersecretion or hyperglycemia in type 2 diabetes [226]. In a cell line that was transfected with the GIP receptor, prolonged incubation with GIP resulted in a reduction of cAMP generation after 16 h, indicating chronic desensitization at the receptor level [227].…”

Section: Differences To Gastric Inhibitory Polypeptide (Gip)mentioning

confidence: 98%

Glucagon-like peptide 1(GLP-1) in biology and pathology

Meier¹,

Nauck²

2005

Diabetes Metab. Res. Rev.

261

186

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Post-translational proteolytic processing of the preproglucagon gene in the gut results in the formation of glucagon-like peptide 1 (GLP-1). Owing to its glucose-dependent insulinotropic effect, this hormone was postulated to primarily act as an incretin, i.e. to augment insulin secretion after oral glucose or meal ingestion. In addition, GLP-1 decelerates gastric emptying and suppresses glucagon secretion. Under physiological conditions, GLP-1 acts as a part of the 'ileal brake', meaning that is slows the transition of nutrients into the distal gut. Animal studies suggest a role for GLP-1 in the development and growth of the endocrine pancreas. In light of its multiple actions throughout the body, different therapeutic applications of GLP-1 are possible. Promising results have been obtained with GLP-1 in the treatment of type 2 diabetes, but its potential to reduce appetite and food intake may also allow its use for the treatment of obesity. While rapid in vivo degradation of GLP-1 has yet prevented its broad clinical use, different pharmacological approaches aiming to extend the in vivo half-life of GLP-1 or to inhibit its inactivation are currently being evaluated. Therefore, antidiabetic treatment based on GLP-1 may become available within the next years. This review will summarize the biological effects of GLP-1, characterize its role in human biology and pathology, and discuss potential clinical applications as well as current clinical studies.

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“…One gut endocrine cell type that is glucose sensitive is the K‐cell that secretes the hormone, GIP. These cells are found predominantly scattered throughout the mucosa in the stomach and upper intestine (114) and secrete GIP in response to ingestion of glucose or a mixed meal in kinetics very similar to that of insulin from pancreatic β‐cells (115, 116). Indeed, in humans the secretory response of both GIP and insulin is comparable over a wide range of oral glucose dosages (117) and is similarly dependent upon the type of carbohydrate consumed (118).…”

Section: Engineering Gut Endocrine Cells To Produce Insulinmentioning

confidence: 99%

Harnessing the gut to treat diabetes

Fujita

Cheung²,

Kieffer

2004

Pediatr Diabetes

Self Cite

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The gut contains one of the largest stem cell populations in the body, yet has been largely overlooked as a source of potentially therapeutic cells. The stem cells reside in the crypts located at the base of the protruding villi, reproduce themselves, and repopulate the gut lining as differentiated cells are sloughed off into the lumen. Some studies have demonstrated that gut stem cells can be isolated and maintained in culture, but the field is currently hampered by the lack of clear markers for these cells. Nevertheless, the relative accessibility of the cells and the similar pathways of differentiation of both intestinal and pancreatic endocrine cells make the gut an attractive potential source of cells to treat diabetes. In particular, it may be possible to recapitulate islet development by the introduction of specific factors to gut stem cells. Alternatively, gut endocrine cells might be coaxed to produce insulin and secrete it into the blood in a meal-responsive manner. Several investigations support the feasibility of both approaches as novel potential therapies for diabetes. Utilizing a patient's own gut cells to re-establish endogenous meal-regulated insulin secretion could represent an attractive approach to ultimately cure diabetes.

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Glucose-Dependent Insulinotropic Polypeptide (GIP)

Cited by 8 publications

References 116 publications

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

Gastric inhibitory polypeptide does not inhibit gastric emptying in humans

Glucagon-like peptide 1(GLP-1) in biology and pathology

Harnessing the gut to treat diabetes

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