title: Characterization of miR-218/322-Stxbp1 pathway in the process of insulin secretion.
abstract: MicroRNAs (miRNAs) have been implicated in a variety of physiological processes, however, the function of miRNAs in insulin secretion and type 2 diabetes is still unclear. Stxbp1 plays an essential role in exocytosis, and is crucial for insulin secretion. In this study, we focused on the molecular mechanism of Stxbp1 in insulin secretion by identifying its upstream regulators: miR-218 and miR-322. The expression of Stxbp1 was significantly increased in isolated mouse islets exposed to high levels of glucose within 1 h; while two of its predicted upstream miRNAs were found to be downregulated. Further study found that miR-218 and miR-322 directly interact with Stxbp1 by targeting the 3'UTR of its mRNA. MIN6 cells overexpressing the two miRNAs showed a sharp decline in insulin secretion and a decreased sensitivity to glucose; while the inhibition of the two miRNAs promoted insulin secretion. However, islets treated with prolonged high levels of glucose, which is known as glucolipotoxicity, displayed relatively high expression of miR-218 and miR-322, and a reduced level of expression of Stxbp1 accompanied by the blocking of insulin secretion. In summary, this study identified a pathway consisting of miR-218/322 and Stxbp1 in insulin secretion, contributing to a network of β-cell function involving miRNA.
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Lang
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ai
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: You
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Departments of EndocrinologyBlood TransfusionChengdu Military General Hospital, Rongdu Road 270, Chengdu, Sichuan 610083, China williamsjin@sinacom.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Jin
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D015870:Gene Expression; D005947:Glucose / Q000502:physiology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D051938:Munc18 Proteins / Q000502:physiology*; D034622:RNA Interference
chemical_list: D020413:3' Untranslated Regions; D007328:Insulin; C547684:MIRN218 microRNA, mouse; C582672:MIRN322 microRNA, mouse; D035683:MicroRNAs; D051938:Munc18 Proteins; C497938:Stxbp1 protein, mouse; D005947:Glucose
keywords: Stxbp1; glucolipotoxicity; insulin secretion; miR-218; miR-322; type 2 diabetes; β-cell function