A5027504612- Diabetes Treatment and Management
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Metabolism, Diabetes, and Cancer
- Growth Hormone and Insulin-like Growth Factors
- Thermoregulation and physiological responses
- Dietary Effects on Health
- Diet, Metabolism, and Disease
- Diabetes and associated disorders
- Hematopoietic Stem Cell Transplantation
- Cellular transport and secretion
- Immune Cell Function and Interaction
- Exercise and Physiological Responses
University of Copenhagen
2019-2024
Gentofte Hospital
2024
Rigshospitalet
2018
Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes
Abstract Background and Purpose The gut hormone glucose‐dependent insulinotropic polypeptide (GIP) signals via the GIP receptor (GIPR), resulting in postprandial potentiation of glucose‐stimulated insulin secretion. translation results from rodent studies to human has been challenged by unexpected effects GIPR‐targeting compounds. We, therefore, investigated variation between species, focusing on GIPR desensitization role C‐terminus. Experimental Approach humans, mice, rats, pigs, dogs cats...
Glucose-dependent insulinotropic polypeptide (GIP) and its receptor (GIPR) are involved in multiple physiological systems related to glucose metabolism, bone homeostasis fat deposition. Recent research has surprisingly indicated that both agonists antagonists of GIPR may be useful the treatment obesity type 2 diabetes, as result weight loss when combined with GLP-1 activation. To understand signaling loss, we examined pharmacological properties two rare missense variants, R190Q (rs139215588)...
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are hormones secreted from the enteroendocrine cells after a meal. They exert their actions through activation of G protein-coupled receptors (R), GIPR GLP-2R, respectively. Both have been reported to influence metabolism. The purpose study was investigate role in regulation lipid bone homeostasis by subchronic treatment with novel GLP-2R antagonists. Rats were injected once daily vehicle, GIPR, or...
Treatment with glucagon receptor antagonists (GRAs) reduces blood glucose but causes dyslipidemia and accumulation of fat in the liver. We investigated acute chronic effects on lipid metabolism mice.Chronic signaling were studied using oral tolerance tests (OLTTs) overnight fasted knockout (Gcgr-/-) mice, C57Bl/6JRj mice treated a antibody (GCGR Ab) or long-acting analogue (GCGA) for eight weeks. Following treatment, liver tissue was harvested RNA-sequencing triglyceride measurements. Acute...
Abstract Context Lost glucagon-like peptide 1 receptor (GLP-1R) function affects human physiology. Objective This work aimed to identify coding nonsynonymous GLP1R variants in Danish individuals link their vitro phenotypes and clinical phenotypic associations. Methods We sequenced 8642 with type 2 diabetes or normal glucose tolerance examined the ability of bind GLP-1 signal transfected cells via cyclic adenosine monophosphate (cAMP) formation β-arrestin recruitment. performed a...
Background and Purpose The gut hormone glucose-dependent insulinotropic polypeptide (GIP) signals via the GIP receptor (GIPR) resulting in postprandial processes such as potentiation of glucose-stimulated insulin secretion. Translation results from rodent to human studies has, however, been challenged by contradictive therapeutic effects GIPR-targeting compounds. We, therefore, investigated variation between species focusing on GIPR desensitization role C-terminus. Experimental Approach...
The molecular sensors underlying nutrient-stimulated GLP-1 secretion are currently being investigated. Peripheral administration of melanocortin-4 receptor (MC4R) agonists have been reported to increase plasma concentrations in mice and humans but it is unknown whether this effect results from a direct on the secreting L-cells intestine, other effects intestine or extra-intestinal effects. We investigated L-cell expression MC4R mouse human by reanalyzing publicly available RNA sequencing...
The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) is secreted from enteroendocrine K cells in the small intestine following food intake. Exogenous GIP stimulates glucagon secretion during fasting at low blood sugar and exerts anabolic effects fat bone healthy individuals. Using receptor antagonist GIP(3-30)NH2, we investigated of endogenous humans fasting. In a randomized, placebo-controlled, double-blind, crossover study comprising two experimental days, 12...
Abstract Design The hormone secretin, best known for regulating pH in the duodenum, has anorectic properties mice proposedly mediated via secretin-induced brown adipose tissue (BAT) activation. We investigated effects of exogenous secretin on ad libitum food intake, BAT activity, and postprandial physiology healthy male volunteers. Methods In a randomized, placebo-controlled, double-blind, crossover study, 25 men underwent two 5-hour i.v. infusions (1 pmol/kg/min) placebo (saline),...
The glucose-dependent insulinotropic polypeptide (GIP) is a 42-residue metabolic hormone that actively being targeted for its regulatory role of glycemia and energy balance. Rational design ligands, however, has been tedious with no structural data the GIP receptor available. This study investigates structure function (GIPR), using homology model based on GLP-1 receptor. Molecular dynamics combined in vitro mutational were used to pinpoint residues play ligand binding and/or activation....