Mechanisms of action of the antidiabetic peptide [S4K]CPF-AM1 in db/db mice
| العنوان: | Mechanisms of action of the antidiabetic peptide [S4K]CPF-AM1 in db/db mice |
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| المؤلفون: | Vishal Musale, Yasser Abdel-Wahab, J. Michael Conlon, Bosede O. Owolabi, R. Charlotte Moffett, Peter R. Flatt |
| المصدر: | Journal of Molecular Endocrinology. 66:115-128 |
| بيانات النشر: | Bioscientifica, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Blood Glucose, Male, 0301 basic medicine, medicine.medical_treatment, AKT1, Peptide, Membrane Potentials, 0302 clinical medicine, Endocrinology, Glucagon-Like Peptide 1, Insulin Secretion, Cyclic AMP, Insulin, chemistry.chemical_classification, biology, Chemistry, Lipids, medicine.anatomical_structure, Liver, Creatinine, Amylases, Body Composition, medicine.medical_specialty, 030209 endocrinology & metabolism, Cell Line, Diabetes Mellitus, Experimental, Islets of Langerhans, 03 medical and health sciences, Downregulation and upregulation, Internal medicine, medicine, Animals, Hypoglycemic Agents, Amino Acid Sequence, Molecular Biology, Protein kinase C, Body Weight, Skeletal muscle, Glucose Tolerance Test, IRS1, Mice, Inbred C57BL, Insulin receptor, 030104 developmental biology, Gene Expression Regulation, biology.protein, Calcium, Energy Intake, Peptides |
| الوصف: | The antidiabetic effects and mechanisms of action of an analogue of a frog skin host-defence peptide belonging to the caerulein-precursor fragment family, [S4K]CPF-AM1 were investigated in db/db mice with a genetically inherited form of degenerative diabetes-obesity. Twice-daily treatment with the peptide (75 nmol/kg body weight) for 28 days significantly decreased blood glucose (P < 0.01) and HbA1c (P < 0.05) and increased plasma insulin (P < 0.05) concentrations with no effect on body weight, energy intake, body composition or plasma lipid profile. Peptide administration improved insulin sensitivity and intraperitoneal glucose tolerance. Elevated biomarkers of liver and kidney function associated with the db/db phenotype were significantly lowered by [S4K]CPF-AM1 administration. Peptide treatment significantly (P < 0.05) increased pancreatic insulin content and improved the responses of isolated islets to established secretagogues. Elevated expression of genes associated with insulin signalling (Slc2a4, Insr, Irs1, Akt1, Pik3ca, Ppm1b) in the skeletal muscle of db/db mice were significantly downregulated by peptide treatment. Genes associated with insulin secretion (Abcc8, Kcnj11, Slc2a2, Cacn1c, Glp1r, Gipr) were significantly upregulated by treatment with [S4K]CPF-AM1. Studies with BRIN-BD1I clonal β-cells demonstrated that the peptide evoked membrane depolarisation, increased intracellular Ca2+ and cAMP and activated the protein kinase C pathway. The data indicate that the antidiabetic properties of [S4K]CPF-AM1 mice are mediated by direct insulinotropic action and by regulation of transcription of genes involved in both the secretion and action of insulin. |
| تدمد: | 1479-6813 0952-5041 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec81080563b6d1fd1f1041e65ead2278Test https://doi.org/10.1530/jme-20-0152Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ec81080563b6d1fd1f1041e65ead2278 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14796813 09525041 |
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