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

Bone ◽  
2020 ◽  
Vol 130 ◽  
pp. 115079 ◽  
Author(s):  
Lærke S. Gasbjerg ◽  
Bolette Hartmann ◽  
Mikkel B. Christensen ◽  
Amalie R. Lanng ◽  
Tina Vilsbøll ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Bone Metabolism ◽  
Gip Receptor

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

2007 ◽  
Vol 388 (2) ◽  
Author(s):  
Victor A. Gault ◽  
Kerry Hunter ◽  
Nigel Irwin ◽  
Brett Greer ◽  
Brian D. Green ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Gip Receptor

scholarly journals GIP(3-30)NH2 is an efficacious GIP receptor antagonist in humans: a randomised, double-blinded, placebo-controlled, crossover study

Diabetologia ◽  
2017 ◽  
Vol 61 (2) ◽  
pp. 413-423 ◽  
Author(s):  
Lærke S. Gasbjerg ◽  
Mikkel B. Christensen ◽  
Bolette Hartmann ◽  
Amalie R. Lanng ◽  
Alexander H. Sparre-Ulrich ◽  
...  
Keyword(s):  
Crossover Study ◽  
Receptor Antagonist ◽  
Double Blinded ◽  
Gip Receptor

Effect of long-term administration of ranitidine, a histamine H2 receptor antagonist, on bone metabolism in young growing rats

2018 ◽  
Vol 70 (5) ◽  
pp. 951-954 ◽  
Author(s):  
Agnieszka Matuszewska ◽  
Beata Nowak ◽  
Diana Jędrzejuk ◽  
Marcin Landwójtowicz ◽  
Ewa Sadanowicz ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Bone Metabolism ◽  
H2 Receptor Antagonist ◽  
Histamine H2 Receptor ◽  
H2 Receptor ◽  
Growing Rats ◽  
Term Administration ◽  
Histamine H2 Receptor Antagonist

scholarly journals Evidence that the major degradation product of glucose-dependent insulinotropic polypeptide, GIP(3-42), is a GIP receptor antagonist in vivo

2002 ◽  
Vol 175 (2) ◽  
pp. 525-533 ◽  
Author(s):  
VA Gault ◽  
JC Parker ◽  
P Harriott ◽  
PR Flatt ◽  
FP O'Harte
Keyword(s):  
Insulin Secretion ◽  
Receptor Antagonist ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Chinese Hamster ◽  
Lung Fibroblasts ◽  
Incretin Hormone ◽  
Ionisation Mass Spectrometry ◽  
Gip Receptor

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is rapidly degraded in the circulation by dipeptidyl peptidase IV forming the N-terminally truncated peptide GIP(3-42). The present study examined the biological activity of this abundant circulating fragment peptide to establish its possible role in GIP action. Human GIP and GIP(3-42) were synthesised by Fmoc solid-phase peptide synthesis, purified by HPLC and characterised by electrospray ionisation-mass spectrometry. In GIP receptor-transfected Chinese hamster lung fibroblasts, GIP(3-42) dose dependently inhibited GIP-stimulated (10(-7) M) cAMP production (up to 75.4+/-5.4%; P<0.001). In BRIN-BD11 cells, GIP(3-42) was significantly less potent at stimulating insulin secretion (1.9- to 3.2-fold; P<0.001), compared with native GIP and significantly inhibited GIP-stimulated (10(-7) M) insulin secretion with maximal inhibition (48.8+/-6.2%; P<0.001) observed at 10(-7) M. In (ob/ob) mice, administration of GIP(3-42) significantly inhibited GIP-stimulated insulin release (2.1-fold decrease; P<0.001) and exaggerated the glycaemic excursion (1.4-fold; P<0.001) induced by a conjoint glucose load. These data indicate that the N-terminally truncated GIP(3-42) fragment acts as a GIP receptor antagonist, moderating the insulin secreting and metabolic actions of GIP in vivo.

scholarly journals Deoxynivalenol (Vomitoxin)-Induced Anorexia Is Induced by the Release of Intestinal Hormones in Mice

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 512
Author(s):  
Jianming Yue ◽  
Dawei Guo ◽  
Xiuge Gao ◽  
Jiacai Wang ◽  
Eugenie Nepovimova ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Experimental Model ◽  
Intraperitoneal Injection ◽  
Direct Injection ◽  
Critical Role ◽  
Significant Part ◽  
Intestinal Hormones ◽  
Cck Receptor Antagonist ◽  
Gip Receptor

Deoxynivalenol (DON), also known as vomitoxin, is a mycotoxin that can cause antifeeding and vomiting in animals. However, the mechanism of DON inducing anorexia is complicated. Studies have shown that intestinal hormones play a significant part in the anorexia caused by DON. We adopted the “modeling of acute antifeeding in mice” as the basic experimental model, and used two methods of gavage and intraperitoneal injection to explore the effect of intestinal hormones on the antifeedant response induced by DON in mice. We found that 1 and 2.5 mg/kg·bw of DON can acutely induce anorexia and increase the plasma intestinal hormones CCK, PYY, GIP, and GLP-1 in mice within 3 h. Direct injection of exogenous intestinal hormones CCK, PYY, GIP, and GLP-1 can trigger anorexia behavior in mice. Furthermore, the PYY receptor antagonist JNJ-31020028, GLP-1 receptor antagonist Exendin(9-39), CCK receptor antagonist Proglumide, GIP receptor antagonist GIP(3-30)NH2 attenuated both intestinal hormone and DON-induced anorectic responses. These results indicate that intestinal hormones play a critical role in the anorexia response induced by DON.

scholarly journals Glucagon receptor antagonist and GIP agonist combination for diet-induced obese mice

2016 ◽  
Vol 229 (3) ◽  
pp. 319-330 ◽  
Author(s):  
L M McShane ◽  
N Irwin ◽  
D O’Flynn ◽  
Z J Franklin ◽  
C M Hewage ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Combined Treatment ◽  
Receptor Activation ◽  
Daily Injection ◽  
Oral Glucose ◽  
Receptor Signaling ◽  
Obese Mice ◽  
Glucagon Receptor ◽  
Glucagon Receptor Antagonist ◽  
Gip Receptor

Ablation of glucagon receptor signaling represents a potential treatment option for type 2 diabetes (T2DM). Additionally, activation of glucose-dependent insulinotropic polypeptide (GIP) receptor signaling also holds therapeutic promise for T2DM. Therefore, this study examined both independent and combined metabolic actions of desHis1Pro4Glu9(Lys12PAL)-glucagon (glucagon receptor antagonist) and d-Ala2GIP (GIP receptor agonist) in diet-induced obese mice. Glucagon receptor binding has been linked to alpha-helical structure and desHis1Pro4Glu9(Lys12PAL)-glucagon displayed enhanced alpha-helical content compared with native glucagon. In clonal pancreatic BRIN-BD11 beta-cells, desHis1Pro4Glu9(Lys12PAL)-glucagon was devoid of any insulinotropic or cAMP-generating actions, and did not impede d-Ala2GIP-mediated (P<0.01 to P<0.001) effects on insulin and cAMP production. Twice-daily injection of desHis1Pro4Glu9(Lys12PAL)-glucagon or d-Ala2GIP alone, and in combination, in high-fat-fed mice failed to affect body weight or energy intake. Circulating blood glucose levels were significantly (P<0.05 to P<0.01) decreased by all treatments regimens, with plasma and pancreatic insulin elevated (P<0.05 to P<0.001) in all mice receiving d-Ala2GIP. Interestingly, plasma glucagon concentrations were decreased (P<0.05) by sustained glucagon inhibition (day 28), but increased (P<0.05) by d-Ala2GIP therapy, with a combined treatment resulting in glucagon concentration similar to saline controls. All treatments improved (P<0.01) intraperitoneal and oral glucose tolerance, and peripheral insulin sensitivity. d-Ala2GIP-treated mice showed increased glucose-induced insulin secretion in response to intraperitoneal and oral glucose. Metabolic rate and ambulatory locomotor activity were increased (P<0.05 to P<0.001) in all desHis1Pro4Glu9(Lys12PAL)-glucagon-treated mice. These studies highlight the potential of glucagon receptor inhibition alone, and in combination with GIP receptor activation, for T2DM treatment.

scholarly journals Increased Body Weight and Fat Mass After Subchronic GIP Receptor Antagonist, but Not GLP-2 Receptor Antagonist, Administration in Rats

2019 ◽  
Vol 10 ◽  
Author(s):  
Sara Baldassano ◽  
Lærke Smidt Gasbjerg ◽  
Hüsün Sheyma Kizilkaya ◽  
Mette Marie Rosenkilde ◽  
Jens Juul Holst ◽  
...  
Keyword(s):  
Body Weight ◽  
Receptor Antagonist ◽  
Fat Mass ◽  
Gip Receptor

Dose‐dependent efficacy of the glucose‐dependent insulinotropic polypeptide ( GIP) receptor antagonist GIP (3‐30) NH 2 on GIP actions in humans

2020 ◽  
Vol 23 (1) ◽  
pp. 68-74 ◽  
Author(s):  
Lærke Smidt Gasbjerg ◽  
Emilie J. Bari ◽  
Signe Stensen ◽  
Bjørn Hoe ◽  
Amalie R. Lanng ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Dose Dependent ◽  
Gip Receptor
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