HSP40 ameliorates impairment of insulin secretion by inhibiting huntingtin aggregation in a HD pancreatic beta cell model.
Diabetes frequently develops in Huntington's disease patients. Here, we found that mutant huntingtin forms aggregates in the cytoplasm and reduces insulin secretion from huntingtin transfected pancreatic beta cell lines, NIT-1 cells. Activity of the pro-survival factor, Akt, is enhanced in these cells, which might improve the maintenance of insulin content. Overexpression of heat shock protein 40 (HSP40) inhibits aggregation, reverses impaired insulin release, and blocks the enhancement of Akt activity. These results suggest that impairment of beta cells is mostly linked with the aggregate formation of mutant huntingtin, and that HSP40 ameliorates the malfunction of pancreatic beta cells by inhibiting aggregation.
Ye
Cui-Fang
CF
Division of Histology and Embryology, Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Li
He
H
D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D050956:HSP40 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D050956:HSP40 Heat-Shock Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D007328:Insulin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt