Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes

MOLECULAR AND CELLULAR ENDOCRINOLOGY

卷:447

Article

Shcherbina, L.¹  Edlund, A.¹  Esguerra, J. L. S.¹  Abels, M.¹  Zhou, Y.¹  Ottosson-Laakso, E.¹  Wollheim, C. B.^1,2  Hansson, O.¹  Eliasson, L.¹  Wierup, N.¹ 

[1] Lund Univ, Diabet Ctr, Skane Univ Hosp, Jan Waldenstroms Gata 35, S-21428 Malmo, Sweden

[2] Univ Med Ctr, Dept Cell Physiol & Metab, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland

关键词: Cocaine- and amphetamine-regulated;    transcript;    Beta-cell;    Insulin secretion;    Exocytosis;    INS-1 (832/13);    Human islets;   

DOI  :  10.1016/j.mce.2017.02.027

来源: Elsevier

【 摘 要 】

Impaired beta-cell function is key to the development of type 2 diabetes. Cocaine- and amphetamine regulated transcript (CART) is an islet peptide with insulinotropic and glucagonostatic properties. Here we studied the role of endogenous CART in beta-cell function. CART silencing in INS-1 (832/13) beta-cells reduced insulin secretion and production, ATP levels and beta-cell exocytosis. This was substantiated by reduced expression of several exocytosis genes, as well as reduced expression of genes important for insulin secretion and processing. In addition, CART silencing reduced the expression of a network of transcription factors essential for beta-cell function. Moreover, in RNAseq data from human islet donors, CARTPT expression levels correlated with insulin, exocytosis genes and key beta-cell transcription factors. Thus, endogenous beta-cell CART regulates insulin expression and secretion in INS-1 (832/13) cells, via actions on the exocytotic machinery and a network of beta-cell transcription factors. We conclude that CART is important for maintaining the beta-cell phenotype. (C) 2017 Elsevier B.V. All rights reserved.

【 授权许可】

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