Guo Wei1, Shao Yi1, Dai Yong1, Liu Shaozhuang1, Zhang Guangyong1, Hu Sanyuan2. 1. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China. 2. Department of General Surgery, Qilu Hospital of Shandong University, Jinan, People's Republic of China. Electronic address: husanyuan1962@hotmail.com.
Abstract
BACKGROUND: Duodenal-jejunal bypass (DJB) surgery can improve type 2 diabetes (T2D) dramatically. Accumulating evidence implicates deficiency of hepatic adiponectin signaling as a contributor to gluconeogenesis disorders, and some microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB-induced T2D amelioration. OBJECTIVES: To investigate the essential role of miRNAs in regulation of adiponectin signaling by targeting AdipoR1 in DJB and the underlying mechanisms. SETTING: University Hospital, China. METHODS: We studied hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo rat liver cell lines. Liver tissues and glucose tolerance tests were analyzed in DJB rats injected with lentivirus encoding a miR-320 mimic. RESULTS: Transfection with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream adiponectin signaling; transfection with a miR-320 inhibitor elicited the opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'-untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers. CONCLUSION: miR-320 regulates the adipoR1-mediated amelioration of T2D in DJB and should be explored as a potential target for T2D treatment.
BACKGROUND: Duodenal-jejunal bypass (DJB) surgery can improve type 2 diabetes (T2D) dramatically. Accumulating evidence implicates deficiency of hepaticadiponectin signaling as a contributor to gluconeogenesis disorders, and some microRNAs (miRNAs) regulate adiponectin receptors (AdipoR1, AdipoR2). We investigated the effects of DJB on hepatic gluconeogenesis, lipid metabolism, and inflammation as well as the effects of miRNA-320 (AdipoR1-targeting miRNA) on DJB-induced T2D amelioration. OBJECTIVES: To investigate the essential role of miRNAs in regulation of adiponectin signaling by targeting AdipoR1 in DJB and the underlying mechanisms. SETTING: University Hospital, China. METHODS: We studied hepatic adiponectin signaling changes and hepatic miRNAs involved in a rat model of DJB. We investigated the effects of miR-320 on AdipoR1 signaling in buffalo rat liver cell lines. Liver tissues and glucose tolerance tests were analyzed in DJB rats injected with lentivirus encoding a miR-320 mimic. RESULTS: Transfection with a miR-320 mimic reduced AdipoR1 protein levels and inhibited downstream adiponectin signaling; transfection with a miR-320 inhibitor elicited the opposite effects. A luciferase assay confirmed that miR-320 binds to the 3'-untranslated regions of AdipoR1. Global upregulation of miR-320 expression in DJB rats showed impaired gluconeogenesis, lipid metabolism, and relatively higher expression of inflammation markers. CONCLUSION:miR-320 regulates the adipoR1-mediated amelioration of T2D in DJB and should be explored as a potential target for T2D treatment.
Authors: Kaiping Burrows; Leandra K Figueroa-Hall; Rayus Kuplicki; Jennifer L Stewart; Ahlam M Alarbi; Rajagopal Ramesh; Jonathan B Savitz; T Kent Teague; Victoria B Risbrough; Martin P Paulus Journal: Sci Rep Date: 2022-01-17 Impact factor: 4.379
Authors: Stephen L Atkin; Vimal Ramachandran; Noha A Yousri; Manasi Benurwar; Steven C Simper; Rodrick McKinlay; Ted D Adams; S Hani Najafi-Shoushtari; Steven C Hunt Journal: Front Endocrinol (Lausanne) Date: 2019-01-04 Impact factor: 5.555