A5050283762- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Regulation of Appetite and Obesity
- Receptor Mechanisms and Signaling
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Neuropeptides and Animal Physiology
- Diet and metabolism studies
- Pharmacology and Obesity Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Biochemical Analysis and Sensing Techniques
- Fibroblast Growth Factor Research
- Diabetes Management and Research
- Cancer, Stress, Anesthesia, and Immune Response
- Kruppel-like factors research
- Diabetes and associated disorders
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Hormonal Regulation and Hypertension
- Tryptophan and brain disorders
- Peroxisome Proliferator-Activated Receptors
- Cannabis and Cannabinoid Research
- Sirtuins and Resveratrol in Medicine
- Estrogen and related hormone effects
- Nutrition and Health in Aging
Novo Nordisk (United States)
2017-2025
Eli Lilly (United States)
2025
German Center for Diabetes Research
2014-2020
Helmholtz Zentrum München
2012-2020
University of Alabama at Birmingham
2020
Heinrich Heine University Düsseldorf
2014-2019
Deutsches Diabetes-Zentrum e.V.
2014-2019
Indiana University Bloomington
2013-2019
Technical University of Munich
2012-2018
Center for Environmental Health
2017
Compared to best-in-class GLP-1 mono-agonists, unimolecular co-agonists of and GIP with optimized pharmacokinetics enhance glycemic metabolic benefits in mammals.
Uncertainty exists as to whether the glucose-dependent insulinotropic polypeptide receptor (GIPR) should be activated or inhibited for treatment of obesity. Gipr was recently demonstrated in hypothalamic feeding centers, but physiological relevance CNS remains unknown. Here we show that HFD-fed CNS-Gipr KO mice and humanized (h)GIPR knockin with CNS-hGIPR deletion decreased body weight improved glucose metabolism. In DIO mice, acute central peripheral administration acyl-GIP increases cFos...
Structurally-improved GIP analogs were developed to determine precisely whether receptor (GIPR) agonism or antagonism lowers body weight in obese mice.A series of peptide-based analogs, including structurally diverse agonists and a long-acting antagonist, generated characterized vitro using functional assays cell systems overexpressing human mouse derived receptors. These vivo DIO mice following acute dosing for effects on glycemic control, chronic food intake. Pair-feeding studies indirect...
Abstract The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) mediate insulin responses that are proportionate to nutrient intake facilitate glucose tolerance . GLP-1 receptor (GLP-1R) is an established drug target for the treatment of diabetes obesity 2 , whereas therapeutic potential GIP (GIPR) a subject debate. Tirzepatide agonist at both GIPR GLP-1R highly effective type 3,4 However, although tirzepatide activates in cell lines mouse...
The N-methyl-D-aspartate (NMDA) receptor is a glutamate-activated cation channel that critical to many processes in the brain. Genome-wide association studies suggest glutamatergic neurotransmission and NMDA receptor-mediated synaptic plasticity are important for body weight homeostasis
Incretin-based therapies are highly successful in combatting obesity and type 2 diabetes
High-fat diets (HFDs) lead to obesity and inflammation in the central nervous system (CNS). Estrogens estrogen receptor α (ERα) protect premenopausal females from metabolic complications of obesity-related disease. Here, we demonstrate that hypothalamic PGC-1α regulates ERα vivo. HFD significantly increased palmitic acid (PA) sphingolipids CNS male mice when compared female mice. PA, vitro, HFD, vivo, reduced neurons astrocytes promoted inflammation. depletion with overexpression inhibited...
Glucagon and insulin are commonly believed to have counteracting effects on blood glucose levels. However, recent studies demonstrated that glucagon has a physiologic role activate β cells enhance secretion. To date, the actions of been studied mostly in fasting or hypoglycemic states, yet it is clear mixed-nutrient meals elicit secretion both insulin, suggesting also contributes regulation postprandial state. We hypothesized elevated glycemia seen fed state would allow stimulate reduce...
We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog combination with exendin-4 or FGF21. However, the return action required discontinuation high-fat diet (HFD) exposure. Here we assess whether single peptide possessing balanced coagonism at glucagon-like 1 (GLP-1) and glucagon receptors can restore DIO maintained on HFD. were treated PEG-GLP-1/glucagon (30 nmol/kg every...