title: Reduced expression of the LRP16 gene in mouse insulinoma (MIN6) cells exerts multiple effects on insulin content, proliferation and apoptosis.
abstract: This study assessed the effects of leukemia-related protein 16 (LRP16) on the regulation of pancreatic functions in mouse insulinoma (MIN6) cells. Cells with down-regulated expression of LRP16 were obtained by a shRNA interference strategy. Insulin content and glucose-stimulated insulin secretion (GSIS) were examined by radioimmunoassay. Western blotting was applied to detect protein expression. Glucose-stimulated sub-cellular localization of PDX-1 was immunocytochemically determined. Cell proliferation and apoptosis were detected by flow cytometry. Our results showed that LRP16 regulated insulin content in MIN6 cells by controlling expression of insulin and insulin transcription factors. LRP16 gene silence in MIN6 cells led to reduced cell proliferation and increased apoptosis. The observation of phosphorylation of serine-473 Akt and the localization of PDX-1 to the nucleus under glucose-stimulation exhibited that LRP16 was a component mediating Akt signaling in MIN6 cells. These results suggest that LRP16 plays a key role in maintaining pancreatic β-cell functions and may help us to understand the protective effects of estrogen on the functions of pancreatic β-cells.
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xue
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Lianqing
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qu
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China.
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China. muyiming@301hospital.com.cn.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Mu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002265:Carboxylic Ester Hydrolases; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D020868:Gene Silencing; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens; D007328:Insulin; D014157:Transcription Factors; D002265:Carboxylic Ester Hydrolases; C585648:Macrod1 protein, mouse