P101 [S4K] CPF‐AM1 Mechanisms underlying beneficial actions on pancreatic beta cells in vitro and high‐fat diet‐induced obesity diabetes in vivoYHA ABDEL‐WAHAB, V Musale, BO Owalabi, RC Moffett, OO Ojo, JM Conlon, PR FlattSchool of Biomedical Sciences, Ulster University, Coleraine, UKAims: Previous studies demonstrated insulinotropic activity of CPF‐AM1 (GLGSVLGKALKIGANLL.NH2). In the present study, we extended our investigation on antidiabetic effects of the peptide using the designer novel cationic analogue, [S4K] CPF‐AM1.Methods: Insulin release was assessed using rat (BRIN‐BD11) and human (1.1 B4) pancreatic beta cells. Beta cell proliferation (Ki67) and apoptosis (Tunnel) were examined in BRIN‐BD11 cells. High‐fat mice with obesity diabetes were used to evaluate longer‐term effects of [S4K] CPF‐AM1 (75nmol/kg body weight, i.p.) on blood glucose control and expression of genes involved in insulin signalling and secretion.Results: [S4K] CPF‐AM1 (3μM) produced 321 ± 28% and 260.6 ± 8.07% increase in insulin release from BRIN‐BD11 and 1.1 B4 cells, respectively, compared with control. Culture for 18h with cytokine cocktail [tumour necrosis factor‐α (200U/ml), Interferon gamma (IFNγ) (20U/ml), interleukin‐1β (100U/ml)] decreased proliferation of BRIN‐BD11 cells by 31% compared with control (p < 0.001), whereas [S4K] CPF‐AM1 (10−6M) treated cells exhibited a 33% increase in proliferation. Tunnel‐positive cells were increased by 272% by 18‐h cytokine cocktail treatment but
Diabetic Medicine – Wiley
Published: Jan 1, 2018
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