A5057354484- Diabetes Treatment and Management
- Diet and metabolism studies
- Pancreatic function and diabetes
- Diabetes Management and Research
- Regulation of Appetite and Obesity
- Bariatric Surgery and Outcomes
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Gastrointestinal motility and disorders
- Gastroesophageal reflux and treatments
- Diet, Metabolism, and Disease
- Cardiac electrophysiology and arrhythmias
- Pharmacology and Obesity Treatment
- Metabolism, Diabetes, and Cancer
- Peptidase Inhibition and Analysis
- Gallbladder and Bile Duct Disorders
- Eating Disorders and Behaviors
- Drug Transport and Resistance Mechanisms
- Biochemical Analysis and Sensing Techniques
- Pharmacological Effects and Assays
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Cardiovascular Function and Risk Factors
- Biliary and Gastrointestinal Fistulas
- Nutrition and Health in Aging
- Cholangiocarcinoma and Gallbladder Cancer Studies
University of Copenhagen
2015-2025
Novo Nordisk Foundation
2015-2024
Rigshospitalet
2011-2021
Hvidovre Hospital
2019-2021
Copenhagen University Hospital
2011-2021
The University of Adelaide
2018-2019
Gentofte Hospital
2012-2018
National Health and Medical Research Council
2018
The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are secreted postprandially contribute importantly to postprandial glucose tolerance. In this study, we assessed the individual combined contributions of endogenous GIP GLP-1 changes in glucoregulatory using novel receptor antagonist GIP(3-30)NH2 well-established exendin(9-39)NH2 During 4-h oral tolerance tests (75 g) with an ad libitum meal test, 18 healthy men received on four...
Rapid degradation of glucagon-like peptide-1 (GLP-1) by dipeptidyl peptidase-4 suggests that endogenous GLP-1 may act locally before being degraded. Signaling via the vagus nerve was investigated in 20 truncally vagotomized subjects with pyloroplasty and 10 matched healthy controls. Subjects received (7-36 amide) or saline infusions during after a standardized liquid mixed meal subsequent ad libitum meal. Despite no effect on appetite sensations, significantly reduced food intake control...
Abstract Aims Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used to treat type 2 diabetes and obesity. Albeit cardiovascular outcomes generally improve, treatment with GLP-1 RAs is associated increased heart rate, the mechanism of which unclear. Methods results We employed a large animal model, female landrace pig, multiple in vivo ex approaches including pharmacological challenges, electrophysiology, high-resolution mass spectrometry explore how elicits an increase...
Abstract Context The actions of both endogenous incretin hormones during a meal have not previously been characterized. Objective Using specific receptor antagonists, we investigated the individual and combined contributions glucose-dependent insulinotropic polypeptide (GIP) glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, gallbladder motility. Design Randomized, double-blinded, placebo-controlled, crossover design. Setting On four separate days, liquid...
Abstract Context In males of normal weight, intraduodenal administration calcium enhances the effects amino acid, L-tryptophan (Trp), to suppress energy intake, associated with greater stimulation cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY) secretion (key mechanisms underlying regulation pyloric motility gastric emptying), but not gastrin or glucose-dependent insulinotropic polypeptide (GIP). Objective Given implications for management obesity,...
Abstract Aim Intestinal glucose transport involves SGLT1 in the apical membrane of enterocytes and GLUT2 basolateral membrane. In vivo studies have shown that absorption rates appear to exceed theoretical capacity these transporters, suggesting may occur via additional pathways, which could include passive mechanisms. The aim study was investigate an vitro model, has proven useful for endocrine studies. Methods We studied both transcellular paracellular isolated vascularly perfused rat small...
Glucagon-like peptide 1 (GLP1) is rapidly inactivated by dipeptidyl peptidase 4 (DPP4), but may interact with vagal neurons at its site of secretion. We investigated the role innervation for handling oral and i.v. glucose.Truncally vagotomised subjects (n=16) matched controls (n=10) underwent 50 g-oral glucose tolerance test (OGTT)±vildagliptin, a DPP4 inhibitor (DPP4i) isoglycaemic infusion (IIGI), copying OGTT without DPP4i.Isoglycaemia was obtained 25±2 g in 18±2 (P<0.03); thus,...
Enteropancreatic hormone secretion is thought to include a cephalic phase, but the evidence in humans ambiguous. We studied vagally induced gut responses with and without muscarinic blockade 10 glucose-clamped healthy men (age: 24.5 ± 0.6 yr, means SE; body mass index: 24.0 0.5 kg/m(2); HbA1c: 5.1 0.1%/31.4 mmol/mol). Cephalic activation was elicited by modified sham feeding (MSF, aka "chew spit") or atropine (1 mg bolus 45 min before MSF + 80 ng·kg(-1)·min(-1) for 2 h). To mimic incipient...
Glucagon levels are increasingly being included as endpoints in clinical study design and more than 400 current diabetes-related trials have glucagon an outcome measure. The reliability of immune-based technologies used to measure endogenous concentrations is, therefore, important. We studied the ability immunoassays based on four different detect changes under conditions where strongly suppressed. To our surprise, most advanced technological methods, employing electrochemiluminescence or...
Individuals with obesity due to pathogenic heterozygous melanocortin 4 receptor (MC4R) mutations can be treated efficiently the glucagon-like peptide-1 agonist (GLP-1 RA) liraglutide. Here, we report effect of 16 weeks liraglutide 3 mg/day treatment in a woman morbid and type 2 diabetes (T2D) homozygous MC4R mutation. The body weight loss was 9.7 kg, similar mutation carriers common obesity. In addition, led clinically relevant decreases fasting glucose, triglycerides, systolic blood...
Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extrapancreatic effects, including renal effects. Some of these effects are attenuated in hypertensive rats, where expression receptors reduced. Here, we assessed the and vascular function kidneys from young prehypertensive rats. We examined GLP-1-induced vasodilation vasculature wild-type (WT) receptor knockout mice using wire pressure myography isolated...
Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine cells. An N-terminally degraded metabolite, PYY3–36, has anorexigenic effects, which makes the PYY system target for obesity treatment. However, little known about kinetics and degradation products of PYY. A related peptide, Neuropeptide Y (NPY), may be C-terminus. We therefore investigated after in vitro incubations porcine plasma blood vivo by infusing PYY3–36 into multicatheterized pigs (n = 7) (2...
Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weight-loss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how triggers incretin following RYGB could lead new treatments diabetes obesity. In vitro, release depends on absorption via sodium-glucose cotransporter 1 (SGLT1). We investigated the...
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-2 (GLP-2) are gut hormones secreted in response to food ingestion, they have been suggested regulate bone turnover. In humans, exogenous GIP GLP-2 acutely inhibit resorption as measured by circulating levels of carboxy-terminal type 1 collagen crosslinks (CTX). The objective was study the individual combined acute effects on turnover postmenopausal women during nighttime - a period increased resorption. Using...
The importance of vagal efferent signaling for the insulinotropic and glucagonostatic effects glucagon-like peptide-1 (GLP-1) was investigated in a randomized single-blinded study. Healthy male participants (n = 10) received atropine to block cholinergic transmission or saline infusions on separate occasions. At t 15 min, plasma glucose clamped at 6 mmol/l. GLP-1 infused low dose (0.3 pmol·kg(-1)·min(-1)) from 45-95 min higher (1 95-145 min. Atropine blocked muscarinic, transmission, as...
The mechanisms regulating the postprandial suppression of ghrelin secretion remain unclear, but recent observations in rats indicate that an increase duodenal osmolarity is associated with a reduction levels. Several hormones have been implicated regulation ghrelin.We hypothesized intraduodenal infusion hyperosmolar solution would lower plasma concentrations.Eighteen healthy young men were studied after overnight fast on two occasions randomized double-blinded fashion. A nasoduodenal...
Abstract Background Ghrelin, an orexigenic peptide, is secreted from endocrine cells in the gastric mucosa. Circulating levels rise preprandial phase, suggesting anticipatory or cephalic phase of release, and decline postprandial either loss a stimulatory factor inhibition by factors released when nutrients enter intestine. We hypothesized that vagal signals are not required for (i) increase (ii) suppression ghrelin levels. Further, we wanted to investigate hypothesis (iii) glucagon‐like...