GIP Receptor Antagonist, SKL-14959 Indicated Alteration of the Lipids Metabolism to Catabolism by the Inhibition of Plasma LPL Activity, Resulting in the Suppression of Weight Gain on Diets-Induced Obesity Mice

Hormonal replacement therapy (HRT) has failed to provide a cardioprotective action in postmenopausal women, and thus alternative pharmacological approaches are required. The present study examined the therapeutic potential of the partial estrogen receptor agonist tamoxifen and the angiotensin II type-1 receptor antagonist irbesartan on the hemodynamic profile of ovariectomized (OVX) female SpragueDawley rats (911 weeks). Three weeks following ovariectomy, uterine atrophy was evident and body weight was increased as compared with sham-operated animals. Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and mean arterial pressure (MAP) were significantly increased in the OVX rats as compared with sham rats. One week following ovariectomy, rats were treated with either tamoxifen (10 mg kg1 day1) or irbesartan (40 mg kg1 day1) for a period of 2 weeks. The administration of tamoxifen to OVX rats partially reversed uterine atrophy and prevented body weight gain, albeit body weight remained significantly lower than in sham-operated animals. LVSP and LVEDP were normalized in the tamoxifen-treated OVX rats, whereas MAP remained elevated. Irbesartan partially reduced the body weight gain of the OVX rats and did not influence uterine atrophy. LVSP and MAP were normalized in irbesartan-treated OVX rats, whereas LVEDP remained elevated. These data demonstrate that irbesartan rather than tamoxifen was efficacious in normalizing MAP in the OVX rats without a secondary effect on the uterus.Key words: ovariectomy, hemodynamics, tamoxifen, AT1 receptor antagonists.

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GIP’s effect on bone metabolism is reduced by the selective GIP receptor antagonist GIP(3–30)NH2

Bone ◽

10.1016/j.bone.2019.115079 ◽

2020 ◽

Vol 130 ◽

pp. 115079 ◽

Cited By ~ 2

Author(s):

Lærke S. Gasbjerg ◽

Bolette Hartmann ◽

Mikkel B. Christensen ◽

Amalie R. Lanng ◽

Tina Vilsbøll ◽

...

Keyword(s):

Receptor Antagonist ◽

Bone Metabolism ◽

Gip Receptor

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Cannabinoid CB1 receptor antagonist AM251 reduces palatable dessert consumption and body weight gain in female C57B6 mice

Appetite ◽

10.1016/j.appet.2008.04.161 ◽

2008 ◽

Vol 51 (2) ◽

pp. 385

Author(s):

C.M. Mathes ◽

M. Ferrara ◽

N.E. Rowland

Keyword(s):

Body Weight ◽

Weight Gain ◽

Receptor Antagonist ◽

Body Weight Gain ◽

Cb1 Receptor ◽

Cannabinoid Cb1 Receptor ◽

Cb1 Receptor Antagonist ◽

Cannabinoid Cb1 Receptor Antagonist

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Characterisation and glucoregulatory actions of a novel acylated form of the (Pro3)GIP receptor antagonist in type 2 diabetes

Biological Chemistry ◽

10.1515/bc.2007.019 ◽

2007 ◽

Vol 388 (2) ◽

Cited By ~ 7

Author(s):

Victor A. Gault ◽

Kerry Hunter ◽

Nigel Irwin ◽

Brett Greer ◽

Brian D. Green ◽

...

Keyword(s):

Type 2 Diabetes ◽

Receptor Antagonist ◽

Gip Receptor

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Preferential effects of the cannabinoid CB1 receptor antagonist, SR 141716, on food intake and body weight gain of obese (fa/fa) compared to lean Zucker rats

Psychopharmacology ◽

10.1007/s00213-002-1384-8 ◽

2003 ◽

Vol 167 (1) ◽

pp. 103-111 ◽

Cited By ~ 169

Author(s):

S. P. Vickers ◽

L. J. Webster ◽

A. Wyatt ◽

C. T. Dourish ◽

G. A. Kennett

Keyword(s):

Body Weight ◽

Weight Gain ◽

Food Intake ◽

Receptor Antagonist ◽

Body Weight Gain ◽

Zucker Rats ◽

Cannabinoid Cb1 Receptor ◽

Sr 141716 ◽

Cb1 Receptor Antagonist ◽

Cannabinoid Cb1 Receptor Antagonist

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I-M-150847, a novel GLP-1 and GIP receptor dual agonist, reduces body weight gain and improves glycemic control in the rodent model of type 2 diabetes and obesity.

10.1101/2021.12.05.471325 ◽

2021 ◽

Author(s):

PRASENJIT MITRA ◽

Rathin Bauri ◽

Shilpak Bele ◽

Jhansi Edelli ◽

Sourav Dasadhikari ◽

...

Keyword(s):

Type 2 Diabetes ◽

Body Weight ◽

Weight Gain ◽

Body Weight Gain ◽

Single Amino Acid ◽

The Novel ◽

Diabetes And Obesity ◽

Dual Agonist ◽

Gip Receptor

We report the discovery of a novel glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor dual agonist that shows balanced agonism towards both the incretin receptor. The dual agonism of GLP-1 and GIP receptor was achieved by replacing the tryptophan cage of exendin-4 with the C- terminal undecapeptide sequence of oxyntomodulin along with a single amino acid substitution from histidine to tyrosine at the amino terminus of the peptide. The structural modification places lysine 30 of the novel incretin agonist in frame with the corresponding lysine residue in the native GIP sequence. The novel incretin agonist, named I-M-150847, promotes robust glucose-stimulated insulin exocytosis in cultured pancreatic beta cells. Chronic administration of I-M-150847 to mice fed on the high-fat diet improves glucose tolerance, decreases food intake, decreases visceral adiposity and body weight gain demonstrating its therapeutic potential in ameliorating type 2 Diabetes and Obesity.

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GIP receptor antagonist treatment causes weight loss in ovariectomized high fat diet-fed mice

10.22541/au.162303461.16209224/v1 ◽

2021 ◽

Author(s):

Geke Aline Boer ◽

Jenna Hunt ◽

Maria Gabe ◽

Johanne Windeløv ◽

Alexander Sparre-Ulricht ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

Pharmacokinetic Profile ◽

High Fat ◽

Ovariectomized Mice ◽

Gip Receptor

Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in the proximal intestine, may regulate lipid metabolism and adiposity but its exact role in these processes is unclear. Experimental approach We characterized in vitro and in vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed the in vivo pharmacokinetic profile of this antagonist, as well as its ability to affect high-fat diet (HFD)-induced body weight gain in ovariectomized mice during an 8-week treatment period. Key results mGIPAnt-1 showed competitive antagonistic properties to the GIP receptor (GIPR) in vitro as it inhibited GIP-induced cAMP accumulation in COS-7 cells. Furthermore, mGIPAnt-1 was capable of inhibiting GIP-induced glucoregulatory and insulinotropic effects in vivo and has a favourable pharmacokinetic profile with a half-life of 7.2 hours in C57Bl6 female mice. Finally, sub-chronic treatment with mGIPAnt-1 in ovariectomized HFD mice resulted in a reduction of body weight and fat mass. Conclusion and Implications mGIPAnt-1 successfully inhibited acute GIP-induced effects in vitro and in vivo and sub-chronically induces resistance to HFD-induced weight gain in ovariectomized mice. Our results support the development of GIP antagonists for the therapy of obesity.

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