A5036697948- Diabetes Treatment and Management
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Helicobacter pylori-related gastroenterology studies
- Diet, Metabolism, and Disease
- Pharmacology and Obesity Treatment
- Natural Antidiabetic Agents Studies
- Natural Compound Pharmacology Studies
- Neuroendocrine Tumor Research Advances
- Phytochemistry and Biological Activities
University of Otago
2022-2023
University of Auckland
2023
Maurice Wilkins Centre
2023
University of Copenhagen
2016-2022
Novo Nordisk Foundation
2020-2022
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation regulate postprandial metabolism. These hormones known as classical incretin responsible for a major part of insulin release. The effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration GLP-1 agonists capable normalizing glucose control these patients. Over last decades, much research has been focused on...
Glucose-dependent insulinotropic polypeptide (GIP) is best known as an incretin hormone that secreted from K-cells of the proximal intestine, but evidence also implicates a role for GIP in regulating lipid metabolism and adiposity. It well-established receptor knockout (GIPR KO) mice are resistant to diet-induced obesity; however, factors mediating this effect remain unresolved. Accordingly, we aimed elucidate mechanisms leading adiposity resistance GIPR KO with focus on whole-body energy...
The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved this process. phenotype transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or (GIP-DT) was investigated. Mice deficient exhibited lower strength, trabecular mass, number, and cortical thickness, notably due to higher resorption....
The incretin hormone, gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in proximal intestine, may regulate lipid metabolism and adiposity, but its exact role these processes is unclear.We characterized vitro vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. We further assessed pharmacokinetic profile this antagonist, as well ability to affect high-fat diet (HFD)-induced body weight gain ovariectomised mice...
Abstract Loss-of-function (LoF) mutations in KCNQ1 , encoding the voltage-gated K + channel v 7.1, lead to long QT syndrome 1 (LQT1). LQT1 patients also present with post-prandial hyperinsulinemia and hypoglycaemia. In contrast, polymorphisms are associated diabetes, LQTS have a higher prevalence of diabetes. We developed mouse model LoF Kcnq1 mutation using CRISPR-Cas9 hypothesized that this would display prolongation, increased glucose-stimulated insulin secretion allow for interrogation...
Glucagon-like peptide-2 (GLP-2) is a pro-glucagon-derived hormone secreted from intestinal enteroendocrine L cells with actions on gut and bones. GLP-2(1-33) cleaved by DPP-4, forming GLP-2(3-33), having low intrinsic activity competitive antagonism properties at GLP-2 receptors. We created radioligands based these two molecules.The methionine in position 10 of GLP-2(3-33) was substituted tyrosine (M10Y) enabling oxidative iodination, creating [125 I]-hGLP-2(1-33,M10Y) I]-hGLP-2(3-33,M10Y)....
Like other peptide hormones, glucose-dependent insulinotropic polypeptide (GIP) is rapidly cleared from the circulation. Dipeptidyl peptidase-4 (DPP-4) known to be involved. Information on overall pharmacokinetics of GIP in rodents is, however, lacking. We investigated exogenous after intravenous, subcutaneous and intraperitoneal injection with without DPP-4 inhibition conscious female C57Bl/6 mice. Secondly, we compared total intact levels measured by an in-house RIA commercially available...
Butein, a rare chalcone found in the toxic plant Toxicodendron vernicifluum, has been shown to regulate glucose homeostasis via inhibition of nuclear factor kappa-B kinase subunit beta (IKKβ)/nuclear kappa B (NF-κB) pathway brain. Here, we investigated whether nonpoisonous Dahlia pinnata could be source butein as potential treatment for type 2 diabetes (T2D). In mice fed high-fat diet (HFD) induce intolerance, an oral D. petal extract improved tolerance at doses 3.3 mg/kg body weight and 10...
Background: Glucagon-like peptide-2 (GLP-2) is a 33 amino acid pro-glucagon-derived hormone produced in the intestinal enteroendocrine L-cells with trophic actions on both gut and bones. GLP-2(1-33) cleaved by ubiquitous protease dipeptidyl peptidase-4 (DPP-4), resulting GLP-2(3-33) competitive antagonistic properties GLP-2 receptor (GLP-2R). Here we present two new hGLP-2 radioligands different pharmacodynamic profiles. Experimental Approach: The methionine position 10 of was substituted...
Background and purpose The incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), secreted by the enteroendocrine K-cells in proximal intestine, may regulate lipid metabolism adiposity but its exact role these processes is unclear. Experimental approach We characterized vitro vivo antagonistic properties of a novel GIP analogue, mGIPAnt-1. further assessed pharmacokinetic profile this antagonist, as well ability to affect high-fat diet (HFD)-induced body weight gain...