Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat.

Tseng, Chi Chuan; Kieffer, Timothy J.; Jarboe, Linda A.; Usdin, Ted B.; Wolfe, M. Michael

doi:10.1172/jci119060

Cited by 129 publications

(45 citation statements)

References 34 publications

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“…The significance of GIP as a physiological incretin has been emphasized in studies using specific GIP antagonists in rat (56) and inhibition of DP IV activity in GLP-1 receptor knockout mice (57). With the important findings that sulfonylureas improve ␤-cell sensitivity to GIP (58), that smaller fragments of GIP are bioactive (28,29), and in the present report, that even in animals with compromised GIP receptor expression, supraphysiological concentrations of GIP and analogs with improved plasma stability are still capable of improving glucose tolerance, the pharmacological potential of GIP in treatment of human diabetic states is preserved.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase IV-Resistant [d-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats

et al. 2002

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The therapeutic potential of glucose-dependent insulinotropic polypeptide (GIP) for improving glycemic control has largely gone unstudied. A series of synthetic GIP peptides modified at the NH2-terminus were screened in vitro for resistance to dipeptidyl peptidase IV (DP IV) degradation and potency to stimulate cyclic AMP and affinity for the transfected rat GIP receptor. In vitro experiments indicated that [d-Ala2]GIP possessed the greatest resistance to enzymatic degradation, combined with minimal effects on efficacy at the receptor. Thus, [d-Ala2]GIP1–42 was selected for further testing in the perfused rat pancreas and bioassay in conscious Wistar and Zucker rats. When injected subcutaneously in normal Wistar, Fa/?, or fa/fa Vancouver Diabetic Fatty (VDF) Zucker rats, both GIP and [d-Ala2]GIP significantly reduced glycemic excursions during a concurrent oral glucose tolerance test via stimulation of insulin release. The latter peptide displayed greater in vivo effectiveness, likely because of resistance to enzymatic degradation. Hence, despite reduced bioactivity in diabetic models at physiological concentrations, GIP and analogs with improved plasma stability still improve glucose tolerance when given in supraphysiological doses, and thus may prove useful in the treatment of diabetic states.

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Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase IV-Resistant [d-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats

et al. 2002

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“…GIP, previously known as gastric inhibitory polypeptide, is secreted from K-cells of the upper small intestine and GLP-1 is secreted from the L-cells of the lower small intestinal mucosa. Their action as incretins has been well documented in both animal (eg, with the use of specific receptor antagonists 5,6 or targeted receptor disruptors 7 ) and human studies. [8][9][10] Both the incretins enhance glucose induced insulin secretion from pancreatic β-cells.…”

Section: Introductionmentioning

confidence: 99%

Predicting response to incretin-based therapy

Kalra¹,

Kalra²,

Sahay³

et al. 2011

RRED

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There are two important incretin hormones, glucose-dependent insulin tropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). The biological activities of GLP-1 include stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. GLP-1 appears to have a number of additional effects in the gastrointestinal tract and central nervous system. Incretin based therapy includes GLP-1 receptor agonists like human GLP-1 analogs (liraglutide) and exendin-4 based molecules (exenatide), as well as DPP-4 inhibitors like sitagliptin, vildagliptin and saxagliptin. Most of the published studies showed a significant reduction in HbA 1c using these drugs. A critical analysis of reported data shows that the response rate in terms of target achievers of these drugs is average. One of the first actions identified for GLP-1 was the glucose-dependent stimulation of insulin secretion from islet cell lines. Following the detection of GLP-1 receptors on islet beta cells, a large body of evidence has accumulated illustrating that GLP-1 exerts multiple actions on various signaling pathways and gene products in the β cell. GLP-1 controls glucose homeostasis through well-defined actions on the islet β cell via stimulation of insulin secretion and preservation and expansion of β cell mass. In summary, there are several factors determining the response rate to incretin therapy. Currently minimal clinical data is available to make a conclusion. Key factors appear to be duration of diabetes, obesity, presence of autonomic neuropathy, resting energy expenditure, plasma glucagon levels and plasma free fatty acid levels. More clinical evidence is required to identify the factors affecting response rate to incretin therapy.

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“…Measurements were performed at baseline and at 30 and 90 min after initiating insulin infusion. These time points were selected to reflect times at which plasma insulin concentration increases most markedly after a meal (12,13).…”

mentioning

confidence: 99%

Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow

et al. 2002

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Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat.

Cited by 129 publications

References 34 publications

Dipeptidyl Peptidase IV-Resistant [d-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats

Dipeptidyl Peptidase IV-Resistant [d-Ala2]Glucose-Dependent Insulinotropic Polypeptide (GIP) Improves Glucose Tolerance in Normal and Obese Diabetic Rats

Predicting response to incretin-based therapy

Skeletal Muscle Microvascular Recruitment by Physiological Hyperinsulinemia Precedes Increases in Total Blood Flow

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