Therapeutic potential for GIP receptor agonists and antagonists

Irwin, Nigel; Flatt, Peter R.

doi:10.1016/j.beem.2009.03.001

Cited by 93 publications

(92 citation statements)

References 102 publications

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“…Past studies have shown that GIP has a significant role in metabolic control (74), and our results advance the understanding of GIP biology by establishing an insulin-sensitizing role in adipocytes. GIP serum levels and signaling are altered in obesity and type 2 diabetes mellitus (31,75), and our study suggests that normalizing GIP function might contribute to improvements in metabolism through effects on insulin sensitivity in addition to effects on glucose-stimulated insulin secretion and the control of lipolysis.…”

Section: Discussionsupporting

confidence: 67%

Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase

Mohammad

Ramos

Buck

et al. 2011

Journal of Biological Chemistry

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Background: GIP is a gut hormone secreted in response to nutrient intake. Results: GIP has an insulin-sensitizing effect on adipose via activation of the cAMP/PKA/CREB and p110␤ PI3K. Conclusion: These data define a novel signal transduction pathway modulating insulin action in adipocytes. Significance: Insulin-sensitizing activity points to a central role for GIP in coordinating intestinal nutrient sensing and regulation of metabolism.

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Section: Discussionsupporting

confidence: 67%

Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase

Mohammad

Ramos

Buck

et al. 2011

Journal of Biological Chemistry

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“…Interestingly, both activation and inhibition of GIP receptors has been postulated as a possible treatment option for type 2 diabetes and obesity [45]. Thus, GIP receptor agonism augments beta cell-induced glucose-dependent insulin secretion, akin to the actions of clinically approved GLP-1 mimetics [3].…”

Section: Resultsmentioning

confidence: 99%

An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice

Hasib

Gault

et al. 2016

Diabetologia

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Aims/hypothesis Glucose-dependent insulinotropic polypeptide (GIP) and xenin, regulatory gut hormones secreted from enteroendocrine K cells, exert important effects on metabolism. In addition, xenin potentiates the biological actions of GIP. The present study assessed the actions and therapeutic utility of a (DAla 2 )GIP/xenin-8-Gln hybrid peptide, in comparison with the parent peptides (DAla 2 )GIP and xenin-8-Gln. Methods Following confirmation of enzymatic stability, insulin secretory activity of (DAla 2 )GIP/xenin-8-Gln was assessed in BRIN-BD11 beta cells. Acute and persistent glucose-lowering and insulin-releasing effects were then examined in vivo. Finally, the metabolic benefits of twice daily injection of (DAla 2 )GIP/xenin-8-Gln was determined in high-fat-fed mice.

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“…To induce a biological response, it binds to glucosedependent insulinotropic polypeptide receptors (GIPRs), expressed in the endocrine pancreas, gastrointestinal tract, brain, immune and cardiovascular systems, testis, pituitary, lung, kidney, thyroid, several regions in the central nervous system and adipose tissue [6]. Despite a wide distribution of its receptor in the body, the most remarkable action of GIP is to potentiate glucose-stimulated insulin secretion from pancreatic β-cells [7]. Recently, the presence of a functional GIPR has been evidenced at the surface of osteoblasts and osteoclasts [8,9].…”

Section: Introductionmentioning

confidence: 99%

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

Gaudin-Audrain¹,

Irwin²,

Mansur³

et al. 2013

Bone

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A role for the gastro-intestinal tract in controlling bone remodeling is suspected since serum levels of bone remodeling markers are affected rapidly after a meal. Glucose-dependent insulinotropic polypeptide (GIP) represents a suitable candidate in mediating this effect. The aim of the present study was to investigate the effect of total inhibition of GIP signaling on trabecular bone volume, microarchitecture and quality. We used GIP receptor (GIPR) knockout mice and investigated trabecular bone volume and microarchitecture by microCT and histomorphometry. GIPR-deficient animals at 16 weeks of age presented with a significant (20%) increase in trabecular bone mass accompanied by an increase (17%) in trabecular number. In addition, the number of osteoclasts and bone formation rate was significantly reduced and augmented, respectively in these animals when compared with wild-type littermates. These modifications of trabecular bone microarchitecture are linked to a remodeling in the expression pattern of adipokines in the GIPR-deficient mice. On the other hand, despite significant enhancement in bone volume, intrinsic mechanical properties of the bone matrix was reduced as well as the distribution of bone mineral density and the ratio of mature/immature collagen cross-links. Taken together, these results indicate an increase in trabecular bone volume in GIPR KO animals associated with a reduction in bone quality.

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Therapeutic potential for GIP receptor agonists and antagonists

Cited by 93 publications

References 102 publications

Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase

Gastric Inhibitory Peptide Controls Adipose Insulin Sensitivity via Activation of cAMP-response Element-binding Protein and p110β Isoform of Phosphatidylinositol 3-Kinase

An enzymatically stable GIP/xenin hybrid peptide restores GIP sensitivity, enhances beta cell function and improves glucose homeostasis in high-fat-fed mice

Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice

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