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- Title
1257-P: LncRNA Kcnq1ot1 Affects Islet ß-Cell Proliferation and Insulin Secretion.
- Authors
CHEN, YALAN; LI, YANLI; LIU, ZIYU; XU, WEN; LIN, BEISI; SU, YANNA; YAN, JINHUA; LI, WANGEN
- Abstract
Background: Accumulating evidences indicated that long noncoding RNA (LncRNA) were involved in the regulation of diverse biological functions, including the islet function. In our previous study, relatively high expression of LncRNA Kcnq1ot1 was found in the pancreas of normal mice. This study was designed to clarify the role of LncRNA Kcnq1ot1 in pancreatic β cells. Methods: The expressions of LncRNA Kcnq1ot1 in different tissues of normal adult male C57BL/6J mice were detected by qRT-PCR. siRNA was used to downregulate Kcnq1ot1 in MIN6 β cells. The proliferation and apoptosis of β cells were measured by cell counting kit-8 (CCK-8) assay and flow cytometry. Glucose stimulated insulin secretion (GSIS) assay was used to determine the effect of Kcnq1ot1 on insulin secretion of β cells. Moreover, the expressions of cell cycle and insulin related genes (including Ccnd1, Ccnd2, Ins1 and Ins2) were assessed by qRT-PCR. The LncRNA Kcnq1ot1 siRNA and scrambled siRNA were injected into the tail vein of male C57BL/6J, then, the blood glucose and serum insulin levels were measured at 72h after injection. Results: The expression of Kcnq1ot1 was much more abundant in islets of normal male C57BL/6J mice than other tissues. The CCK8 and mRNA expression of Ccnd1 and Ccnd2 showed that the proliferation of Min6 cells was significantly decreased with the downregulation of kcnq1ot1 at 48h and 72h. However, flow cytometry indicated that inhibition of Kcnq1ot1 had no effects on β cells apoptosis. Impaired β-cell function measured by GSIS was found in kcnq1ot1 silenced Min6 cells, along with decreased mRNA levels of INS1 and INS2. Higher glucose and lower serum insulin were detected in the LncRNA Kcnq1ot1 siRNA-treated mice when compared to control group. Conclusions: LncRNA Kcnq1ot1 has multiple effects on β-cell function, including enhanced proliferation and insulin secretion, which suggest Kcnq1ot1 as a new biomarker of islet function. Disclosure: Y. Chen: None. Y. Li: None. Z. Liu: None. W. Xu: None. B. Lin: None. Y. Su: None. J. Yan: None. W. Li: None. Funding: National Natural Science Foundation of China (81800682)
- Publication
Diabetes, 2021, Vol 70, pN.PAG
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db21-1257-P