The Insulinotropic Action of Gastric Inhibitory Polypeptide

Pederson, Raymond A.; Schubert, H; Brown, John C.

doi:10.1139/y75-032

Cited by 55 publications

(20 citation statements)

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“…The finding that the insulinotropic effect of ingested gltucose is absent during euglycemia is particularly intriguing in light of previous observations that fat ingestion, a potent stimuilus to GIP release (14), is accompanied by either no insulin release (24,37) or by a very small increase of about 4 AU/ml (15,23,(38)(39)(40), unless hyperglycemia is present. On the other hand, an insulinotropic effect of GIP independent of hyperglycemia has been reported in the dog (41). However, the dose of GIP infused in this study produced serum GIP levels of -2,500-15,000 pg/ml.…”

Section: Discussioncontrasting

confidence: 69%

Oral Glucose Augmentation of Insulin Secretion

Andersen¹,

Elahi²,

Brown³

et al. 1978

J. Clin. Invest.

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220

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A B S T R A C T Gastric inhibitory polypeptide, or GIP, has been postulated as the major enteric hormonal mediator of insulin release. The release of immunoreactive GIP (IR-GIP) after oral glucose and its role in insulin release was studied in normal men by the glucose clamp technique. In 24 subjects studied with the hyperglycemic clamp, blood glucose was maintained at 125 mg/dl above basal for 2 h via a primedcontinuous IV glucose infusion coupled to a servo-controlled negative feedback system. 40 g glucose per m2 surface area was ingested at 60 min, and the blood glucose was maintained at the steady-state hyperglycemic level. Plasma IR-GIP and insulin (IRI) levels were measured throughout the 2-h period. IR-GIP levels changed little when IV glucose alone was given; the mean basal value was 305+±34 (SEM) pg/ml. After oral glucose, IR-GIP levels began to rise within 10 min and reached a peak within 40 min of 752±105 pg/ml. Plasma IRI responded initially to the square wave of hyperglycemia in the typical biphasic pattern. After oral glucose, plasma IRI levels rose strikingly above the elevated levels produced by hyperglycemia alone, reaching a peak of 170±15 ,tU/ml within 45 min. The time course of the rise in IR-GIP and IRI was nearly identical.To assess whether the maintenance of euglycemia would affect this process, the euglycemic clamp wasThis work was presented in part at the Eastern Section

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Section: Discussioncontrasting

confidence: 69%

Oral Glucose Augmentation of Insulin Secretion

Andersen¹,

Elahi²,

Brown³

et al. 1978

J. Clin. Invest.

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220

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“…Primary among the factors that may determine the insulin secretory responsiveness of the beta cell to GIP is the ambient plasma glucose concentration. Despite the report that the infusion of porcine GIP into animals (which resulted in supraphysiologic concentrations of GIP) was insulinotropic at basal blood glucose levels (20), the infusion of porcine GIP (which results in physiologic levels of GIP) into man is insulinotropic only during hyperglycemia (1,21). Glucose dependency of the insulinotropic action of glucose-stimulated GIP has been demonstrated in a recent report (7) on the basis of changes in serum immunoreactive insulin (rather than C-peptide) after oral glucose during insulin-glucose clamps at euglycemia and supraphysiologic hyperglycemia.…”

Section: Discussionmentioning

confidence: 95%

Interaction of Fat-stimulated Gastric Inhibitory Polypeptide on Pancreatic Alpha and Beta Cell Function

et al. 1980

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A B S T R A C T Gastric inhibitory polypeptide (GIP) is considered to be the principal mediator of the enteroinsular axis. A glucose-insulin clamp technique was used to study the effects of differing blood glucose levels on the insulinotropic and glucagonotropic actions of fat-stimulated GIP in seven healthy subjects, as well as the effect of physiologic hyperinsulinemia on GIP secretion. Blood glucose levels were clamped for 4 h at 43+2 mg/dl (hypoglycemic clamp), 88+1 mg/dl (euglycemic clamp), and 141+2 mg/dl (hyperglycemic clamp) in the presence of a constant insulin infusion (100 mU/kg per h).Under hypoglycemic clamp conditions there was no increase in C-peptide nor glucagon after Lipomul ingestion, despite an increase of GIP of 51.7±8.7 ng/ml per 120 min. Under euglycemic clamp conditions, small and inconsistent increases in C-peptide and glucagon were observed after fat ingestion and a concomitant increase of GIP of 35.2±9.4 ng/ml per 120 min. Under hyperglycemic clamp conditions after fat ingestion and a GIP increase of 24.0±5.7 ng/ml per 120 min, C-peptide increased from 6.4±5 ng/ml to 11.0±1.1 ng/ml (P < 0.01) but glucagon did not change. These findings confirm that in healthy man GIP exerts its insulinotropic properties only under hyperglycemic conditions and indicate that GIP is not glucagonotropic.Under euglycemic clamp conditions (plasma glucose, 89±1 mg/dl) and physiologic hyperinsulinemia (serum immunoreactive insulin, 137±3 ,uU/ml) GIP responses to fat ingestion (39.7±9.8 ng/ml per 120 min) were not different from the GIP responses to fat ingestion in the absence of hyperinsulinemia (39.7±11.1 ng/ml per 120 min). Therefore, insulin under normogly- cemic conditions does not exert an inhibitory effect on fat-stimulated GIP secretion. The higher GIP response to oral fat in the hypoglycemic clamp, and the lower GIP response in the hyperglycemic clamp compared to the response in the euglycemic clamp suggests an effect of glycemia itself on GIP secretion in the presence of hyperinstulinemia.

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“…Targets for the hormone include fundic cells of the stomach, where GIP has been shown to inhibit acid secretion (49), and ␤-cells of the pancreatic islets, where GIP potentiates insulin release (15,39). Because of its insulin-releasing properties, GIP has been designated a physiological incretin, the proposed substance that mediates the enteroinsular axis and appears to play an important role in the maintenance of glucose homeostasis.…”

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confidence: 99%

Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene

Boylan

Jepeal

Wolfe

2006

American Journal of Physiology-Endocrinology and Metabolism

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-The physiological effects of glucose-dependent insulinotropic polypeptide (GIP) are mediated through specific receptors expressed on target cells. Because aberrant GIP receptor (GIPR) expression has been implicated in abnormal GIP responses associated with type 2 diabetes mellitus and food-induced Cushing's syndrome, we sought to identify factors that regulate the GIPR. We previously demonstrated that sequences between Ϫ1 and Ϫ100 of the GIPR gene were sufficient to direct transcription in a rat insulinoma cell line (RIN38). In the present study, we compared the 5Ј-flanking regions of the rat and human GIPR gene and demonstrated 88% identity within the first 92 bp. Subsequent serial deletion analyses showed that the region between Ϫ85 and Ϫ40 is essential for maximal promoter activity. Within this region, we identified three putative Sp1 binding motifs, located at positions Ϫ77, Ϫ60, and Ϫ50, that can specifically bind both Sp1 and Sp3. Whereas mutation of the Sp1 sites at Ϫ50 and Ϫ60 led to 36 and 40% reduction in promoter activity, respectively, mutation of the Sp1 motif at Ϫ70 did not affect promoter activity. Cotransfection of S2 Schneider cells with GIPR-luciferase chimeric constructs and either Sp1 or Sp3 expression vectors indicated that both Sp1 and the long form of Sp3 activate transcription through binding to the Sp1 sites located between Ϫ100 and Ϫ40. Lastly, chromatin immunoprecipitation analyses revealed that both Sp1 and Sp3 bind to the GIPR promoter region in RIN38 cells. These results indicate that cellspecific expression of GIPR is associated with the binding of the transcription factors Sp1 and Sp3 to the GIPR promoter. gastric inhibitory polypeptide; transcription factors; RIN38 cells; insulinoma; rat-2 cells; chromatin immunoprecipitation assay GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE (GIP) is a member of the secretin

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The Insulinotropic Action of Gastric Inhibitory Polypeptide

Cited by 55 publications

References 0 publications

Oral Glucose Augmentation of Insulin Secretion

Oral Glucose Augmentation of Insulin Secretion

Interaction of Fat-stimulated Gastric Inhibitory Polypeptide on Pancreatic Alpha and Beta Cell Function

Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene

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