The p66Shc Protein Mediates Insulin Resistance and Secretory Dysfunction in Pancreatic β-Cells Under Lipotoxic Conditions

• DOI: 10.2337/db21-1066
• Publication Date: 2022-05-25T13:48:58Z
• Authors: Giuseppina Biondi; Nicola Marrano; Lucia Dipaola; Anna Borrelli; Martina Rella; Rossella D’Oria; Valentina A. Genchi; Cristina Caccioppoli; Immacolata Porreca; Angelo Cignarelli; Sebastio Perrini; Piero Marchetti; Leonardo Vincenti; Luigi Laviola; Francesco Giorgino; Annalisa Natalicchio
• Keywords: Lipotoxicity; Insulin receptor substrate; IRS1

We evaluated the role of p66Shc redox adaptor protein in pancreatic β-cell insulin resistance that develops under lipotoxic conditions and with excess body fat. Prolonged exposure to palmitate vitro or presence overweight/obesity augmented expression levels caused an impaired ability exogenous increase cellular content secreted C-peptide INS-1E cells human murine islets. In cells, knockdown resulted enhanced insulin-induced augmentation secretion prevented impair these effects insulin. Conversely, overexpression both absence palmitate. Under condition, are mediated by a p53-induced JNK-induced phosphorylation at Ser36 appear involve ribosomal S6 kinase Thr389 receptor substrate 1 Ser307, resulting inhibition insulin-stimulated B Ser473. Thus, mediates function induced saturated fatty acids