Type 2 diabetes mellitus is characterized by insulin ***,the complete molecular mechanism remains *** this study,zebrafish were fed a long-term highfat diet to induce type 2 diabetes,which resulted in a higher body we...
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Type 2 diabetes mellitus is characterized by insulin ***,the complete molecular mechanism remains *** this study,zebrafish were fed a long-term highfat diet to induce type 2 diabetes,which resulted in a higher body weight,body mass index,more lipid vacuoles in liver,increased insulin transcription level in liver,brain and muscle,and high fasting blood glucose in the high-fat diet ***,the transcription levels of insulin substrate-2 and glucose transporter 2 were significantly decreased,indicating insulin signaling pathway and glucose transport impaired in the insulin-targeting *** of the autophagy-related genes,ATG3,ATG4B,ATG5,ATG7 and ATG12 were decreased but autophagy inhibitor gene m-TOR increased,and autophagyflux was inhibited in liver of the high-fat diet *** changes were confirmed in palmitic acid-treated HepG2 ***,in co-immunoprecipitation and subcellular colocalization experiments,the conjunction of preproinsulin with cargo-recognition protein p62 increased,but conjuncts of autophagosome with p62-cargo,lysosomes with p62-cargo,and autolysosomes decreased ***,lysosomes,autolysosomes and conjuncts of p62-insulin localized at the periphery of palmitic acid-treated cells,the margination of lysosomes may mediate deactivation of proteases *** findings suggest that intracellular high-lipid may trigger defective autophagy,impaired downstream signaling of insulin and accumulated intracellular preproinsulin,leading to dysregulation of cell homeostasis mechanism,which may be one of reasons involved in insulin-resistance in type 2 diabetes.
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