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

Effects of endogenous GIP in patients with type 2 diabetes

2021 ◽  
Author(s):  
Signe Stensen ◽  
Lærke S Gasbjerg ◽  
Liva L. Krogh ◽  
Kirsa Skov-Jeppesen ◽  
Alexander H. Sparre-Ulrich ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Receptor Antagonist ◽  
Bone Homeostasis ◽  
Collagen Crosslinks ◽  
Ad Libitum ◽  
Postprandial Insulin ◽  
Gip Receptor

Objective: The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved. Design: A randomized, double-blinded, placebo-controlled, crossover study. Methods: Ten patients with overweight/obesity and type 2 diabetes (mean±SD; HbA1c 52±11 mmol/mol; BMI 32.5±4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1,200 pmol × kg-1 × min-1), or placebo (saline) during two separate, 230-minute, standardized, liquid mixed meal tests followed by an ad libitum meal. Subcutaneous adipose tissue biopsies were analyzed. Results: Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide%±SEM; -14±6%, p=0.021) and peak glucagon (Δ%±SEM; -11±6%, p=0.046), but had no effect on plasma glucose (p=0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX;±SEM; -4.9±2 ng/ml × min, p=0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, ad libitum meal consumption or adipose tissue triglyceride content. Conclusions: Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.

scholarly journals Renal Effects of S18886 (Terutroban), a TP Receptor Antagonist, in an Experimental Model of Type 2 Diabetes

Diabetes ◽  
2007 ◽  
Vol 56 (4) ◽  
pp. 968-974 ◽  
Author(s):  
K. Sebekova ◽  
T. Eifert ◽  
A. Klassen ◽  
A. Heidland ◽  
K. Amann
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Experimental Model ◽  
Renal Effects ◽  
Tp Receptor

scholarly journals The Mineralocorticoid Receptor Antagonist Eplerenone Suppress Interstitial Fibrosis in Subcutaneous Adipose Tissue in Type 2 Diabetes Patients

2020 ◽  
Author(s):  
Ada Admin ◽  
Marie Louise Johansen ◽  
Jaime Ibarrola ◽  
Amaya Fernández-Celis ◽  
Morten Schou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Receptor Antagonist ◽  
Subcutaneous Adipose Tissue ◽  
Mineralocorticoid Receptor ◽  
Prostaglandin D2 ◽  
Type I ◽  
Mineralocorticoid Receptor Antagonist ◽  
Subcutaneous Adipose

Activation of the mineralocorticoid receptor (MR) may promote dysfunctional adipose tissue in patients with type 2 diabetes, where increased pericellular fibrosis has emerged as a major contributor. The knowledge of the association between the MR, fibrosis and the effects of an MR antagonist (MRA) in human adipocytes remains very limited. The present sub-study including 30 participants was prespecified as part of the Mineralocorticoid Receptor Antagonist in type 2 Diabetes (MIRAD) trial, randomizing patients to either high dose eplerenone or placebo for 26 weeks. In adipose tissue biopsies, changes in fibrosis were evaluated by immunohistological examinations and by the expression of mRNA and protein markers of fibrosis. Treatment with an MRA reduced pericellular fibrosis, synthesis of the major subunits of collagen type I and VI, and the profibrotic factor α-smooth muscle actin, as compared to placebo in subcutaneous adipose tissue. Furthermore, we found decreased expression of the MR and downstream molecules neutrophil gelatinase–associated lipocalin, galectin-3, and lipocalin-like prostaglandin D2 synthase with an MRA. In conclusions, we present original data demonstrating reduced fibrosis in adipose tissue with inhibition of the MR, which could be a potential therapeutic approach to prevent the extracellular matrix remodeling of adipose tissue in type 2 diabetes.

scholarly journals Treatment with LY2409021, a glucagon receptor antagonist, increases liver fat in patients with type 2 diabetes

2017 ◽  
Vol 19 (11) ◽  
pp. 1521-1528 ◽  
Author(s):  
Cristina B. Guzman ◽  
Xiaotian M. Zhang ◽  
Rong Liu ◽  
Arie Regev ◽  
Sudha Shankar ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Receptor Antagonist ◽  
Liver Fat ◽  
Glucagon Receptor ◽  
Glucagon Receptor Antagonist
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