Glucoregulatory, endocrine and morphological effects of [P5K]hymenochirin-1B in mice with diet-induced glucose intolerance and insulin resistance
| Autor: | Dinesh K. Srinivasan, Peter R. Flatt, Yasser Abdel-Wahab, J M Conlon, Opeolu O. Ojo, Bosede O. Owolabi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Blood Glucose endocrine system medicine.medical_specialty Time Factors medicine.medical_treatment Incretin 030209 endocrinology & metabolism Type 2 diabetes Diet High-Fat Tissue Culture Techniques 03 medical and health sciences Islets of Langerhans Mice 0302 clinical medicine Insulin resistance Internal medicine Glucose Intolerance medicine Animals Hypoglycemic Agents Insulin Muscle Skeletal Cell Shape Pharmacology biology Pancreatic islets General Medicine medicine.disease Lipids Insulin oscillation IRS1 Insulin receptor Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Gene Expression Regulation biology.protein Insulin Resistance Energy Metabolism Biomarkers Antimicrobial Cationic Peptides Signal Transduction |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 389(7) |
| ISSN: | 1432-1912 |
| Popis: | The frog skin host-defence peptide hymenochirin-1B has been shown to stimulate insulin release in vitro from isolated pancreatic islets and BRIN-BD11 clonal β-cells. This study examines the effects of 28-day administration of a more potent analogue [P5K]hymenochirin-1B ([P5K]hym-1B) (75 nmol·kg(-1) body weight) to high-fat-fed mice with obesity, glucose intolerance and insulin resistance. Treatment with [P5K]hym-1B significantly decreased plasma glucose concentrations and improved glucose tolerance, insulin secretion, insulin sensitivity and increased the magnitude of the incretin effect (difference in response to oral vs intraperitoneal glucose loads). Responses to established insulin secretagogues were greater in islets isolated from treated animals compared with saline-treated controls. [P5K]hym-1B administration significantly decreased total islet area and β- and α-cell areas, and resulted in lower concentrations of circulating triglycerides and plasma and pancreatic glucagon. Peptide treatment had no effect on food intake, body weight, indirect calorimetry or circulating concentrations of amylase and marker enzymes of liver and kidney function. RT-PCR demonstrated that the Insr (insulin receptor) gene and genes involved in insulin signalling (Slc2a4, Irs1, Pik3ca, Akt1 and Pkd1) were significantly up-regulated in skeletal muscle from animals treated with [P5K]hym-1B. Expression of the Glp1r (GLP-1 receptor) and Gipr (GIP receptor) genes was significantly elevated in islets from peptide-treated mice. These data suggest that [P5K]hym-1B shows potential for development into an agent for treating patients with type 2 diabetes. |
| Databáze: | OpenAIRE |
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