A5014405609- Diabetes Treatment and Management
- Regulation of Appetite and Obesity
- Diet and metabolism studies
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Neuropeptides and Animal Physiology
- Adipose Tissue and Metabolism
- Hormonal Regulation and Hypertension
- Bariatric Surgery and Outcomes
- Renin-Angiotensin System Studies
- Diabetes and associated disorders
- Birth, Development, and Health
- Fibroblast Growth Factor Research
- Molecular Biology Techniques and Applications
- Ion channel regulation and function
- Biochemical effects in animals
- Single-cell and spatial transcriptomics
- Computational Drug Discovery Methods
- Metabolomics and Mass Spectrometry Studies
- Enhanced Recovery After Surgery
- Viral Infectious Diseases and Gene Expression in Insects
- Receptor Mechanisms and Signaling
- Diabetes Management and Research
- Pharmacological Effects of Natural Compounds
- Chemical Synthesis and Analysis
Gubra (Denmark)
2013-2024
Novo Nordisk (United States)
2019-2020
Novo Nordisk Foundation
2014-2015
University of Copenhagen
2013-2015
Novo Nordisk Foundation Center for Basic Metabolic Research
2015
Zealand Pharma (Denmark)
2014
Liraglutide is a glucagon-like peptide-1 (GLP-1) analog marketed for the treatment of type 2 diabetes. Besides lowering blood glucose, liraglutide also reduces body weight. It not fully understood how induces weight loss or to what degree acts directly in brain. Here, we determined that does activate GLP-1-producing neurons hindbrain, and liraglutide-dependent reduction rats was independent GLP-1 receptors (GLP-1Rs) vagus nerve, area postrema, paraventricular nucleus. Peripheral injection...
Background and Aims Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) peptide YY (PYY) are thought play central role in anti-diabetic effects RYGB; therefore, an improved understanding intestinal endocrine adaptability is considered pivotal. Methods The full rostrocaudal extension was analyzed rats after RYGB...
To characterise changes in pancreatic beta cell mass during the development of diabetes untreated male C57BLKS/J db/db mice.Blood samples were collected from a total 72 mice aged 5, 6, 8, 10, 12, 14, 18, 24 and 34 weeks, for measurement terminal blood glucose, HbA1c, plasma insulin, C-peptide. Pancreata removed quantification mass, islet numbers as well proliferation apoptosis by immunohistochemistry stereology.Total increased significantly 2.1 ± 0.3 mg 5 weeks to peak value 4.84 0.26 (P <...
Neurotensin (NT) is a peptide expressed in the brain and gastrointestinal tract. Brain NT inhibits food intake, but effects of peripheral are less investigated. In this study, decreased intake both mice rats, which was abolished by antagonist. Using c-Fos immunohistochemistry, we found that activated brainstem hypothalamic regions. The anorexigenic effect preserved vagotomized lasted shorter than sham-operated mice. This combination with strong increase activation area postrema after ip...
Aim Unlike rats and mice, hamsters develop hypercholesterolemia, hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is hallmark of human obesity, we aimed to characterize novel diet-induced obesity (DIO) hypercholesterolemia Golden Syrian hamster model. Methods Results Hamsters highly palatable fat- sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, fat accumulation impaired glucose tolerance. Cholesterol supplementation the evoked additional...
Background: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular renal outcomes in type 2 diabetes patients. Here, we characterized the effect long-acting GLP-1R agonist semaglutide alone combination with an ACE inhibitor (lisinopril) a model hypertension-accelerated, advanced DKD facilitated by adeno-associated...
Antidiabetic treatments aiming to preserve or even increase <i>β</i>-cell mass are currently gaining increased interest. Here we investigated the effect of chronic treatment with novel glucagon-like peptide-1 (GLP-1)–gastrin dual agonist ZP3022 (HGEGTFTSDLSKQMEEEAVRLFIEWLKN-8Ado-8Ado-YGWLDF-NH2) on glycemic control, and proliferation, islet number. Male <i>db/db</i> mice were treated ZP3022, liraglutide, vehicle for 2, 4, 8 weeks, terminal assessment hemoglobin A1c, basal blood glucose,...
Neuromedin U (NMU) is a 25 amino acid peptide expressed and secreted in the brain gastrointestinal tract. Data have shown that peripheral administration of human NMU decreases food intake body weight improves glucose tolerance mice, suggesting receptors constitute possible anti-diabetic anti-obesity drug target. However, clinical use native hampered by poor pharmacokinetic profile. In current study, we report vitro vivo data from series novel lipidated analogs. plasma stability studies were...
Peptide-based drug discovery has surged with the development of peptide hormone-derived analogs for treatment diabetes and obesity. Machine learning (ML)-enabled quantitative structure–activity relationship (QSAR) approaches have shown great promise in small molecule but been less successful due to limited data availability. We developed a platform called streaMLine, enabling rigorous design, synthesis, screening, ML-driven analysis large libraries. Using this study systematically explored...
Background GTP cyclohydrolase 1 (GTP-CH1), the rate-limiting enzyme in synthesis of tetrahydrobiopterin (BH4), encoded by GCH1 gene, has been implicated development and maintenance inflammatory pain rats. In humans, homozygous carriers a “pain-protective” (PP) haplotype gene have identified exhibiting lower sensitivity, but only following sensitisation. Ex vivo, PP is associated with decreased induction after stimulation, whereas baseline BH4 production not affected. Contrary, loss function...
Bariatric surgery is currently the most effective treatment of obesity, which has spurred an interest in developing pharmaceutical mimetics. It thought that marked body weight-lowering effects bariatric involve stimulated secretion appetite-regulating gut hormones, including glucagon-like peptide 1. We here report intestinal expression secretin markedly upregulated a rat model Roux-en-Y gastric bypass, suggesting additional role beneficial metabolic bypass. therefore developed novel...
Abstract Dopamine‐producing tyrosine hydroxylase ( TH ) neurones in the hypothalamic arcuate nucleus ARC have recently been shown to be involved ghrelin signalling and body weight homeostasis. In present study, we investigate role of intracellular regulator RhoA response peripheral hormones. Diet‐induced obesity was found associated with increased phosphorylation , indicating obesity‐associated activity neurones. Mice which specifically knocked out ‐RhoA −/− mice) were more sensitive...
VGF is a peptide precursor expressed in neuroendocrine cells that suggested to play role the regulation of energy homeostasis. proteolytically cleaved yield multiple bioactive peptides. However, specific actions VGF-derived peptides on homeostasis remain unclear. The aim present work was investigate and explore pharmacological body weight preclinical animal models. (NERP-1, NERP-2, PGH-NH2, PGH-OH, NERP-4, TLQP-21, TLQP-30, TLQP-62, HHPD-41, AQEE-30, LQEQ-19) were synthesized screened for...
Reelin (RELN) is a large glycoprotein involved in synapse maturation and neuronal organization throughout development. Deficits RELN signaling contribute to multiple psychological disorders, such as autism spectrum disorder, schizophrenia, bipolar disorder. Nutritional stress alters expression brain regions associated with these disorders; however, the involvement of neural circuits energy metabolism unknown. The receptors apolipoprotein E receptor 2 (ApoER2) very low-density lipoprotein...
Abstract Fibroblast growth factor 21 (FGF21) induces weight loss in mouse, monkey, and human studies. In mice, FGF21 is thought to cause by stimulating thermogenesis, but whether increases energy expenditure (EE) primates unclear. Here, we explore the transcriptional response gene networks active adipose tissue of rhesus macaques following FGF21-induced loss. Genes related thermogenesis responded inconsistently treatment However, expression modules involved triglyceride (TG) synthesis...
Abstract Background and Aims The Renin adeno-associated virus (AAV) uninephrectomized (UNx) db/db mouse model of diabetic kidney disease (DKD) recapitulates hallmarks DKD with hypertension, including albuminuria glomerulosclerosis. Despite previous characterization the model, gaps persist in our understanding regarding temporal patterns gene expression pathophysiology glomeruli. This longitudinal study characterizes isolated glomeruli from ReninAAV UNx mice during progression hypertension....
Abstract Background and Aims Obesity, hyperglycemia hypertension are critical risk factors for development of diabetic kidney disease (DKD). Emerging evidence suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular renal outcomes in type 2 diabetes patients. Here, we characterized the effect long-acting GLP-1R agonist semaglutide alone combination with an ACE inhibitor a model hypertension-accelerated, advanced DKD facilitated by adeno-associated...
Abstract BACKGROUND AND AIMS Obesity, hyperglycemia and hypertension are critical risk factors for the onset progression of diabetic kidney disease (DKD). Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors glucagon-like peptide-1 receptor (GLP-1R) agonists improve cardiovascular renal outcomes in type 2 diabetes patients. We have recently profiled effects SGLT2 angiotensin-converting enzyme (ACE) inhibition a model advanced DKD facilitated by adeno-associated...