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

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Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes. / Shcherbina, L; Edlund, A; Esguerra, J L S; Abels, M; Zhou, Y; Ottosson-Laakso, E; Wollheim, C B; Hansson, O; Eliasson, L; Wierup, N.

In: Molecular and Cellular Endocrinology, Vol. 447, 2017, p. 52-60.

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TY - JOUR

T1 - Endogenous beta-cell CART regulates insulin secretion and transcription of beta-cell genes

AU - Shcherbina, L

AU - Edlund, A

AU - Esguerra, J L S

AU - Abels, M

AU - Zhou, Y

AU - Ottosson-Laakso, E

AU - Wollheim, C B

AU - Hansson, O

AU - Eliasson, L

AU - Wierup, N

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.mce.2017.02.027

DO - 10.1016/j.mce.2017.02.027

M3 - Article

VL - 447

SP - 52

EP - 60

JO - Molecular and Cellular Endocrinology

T2 - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 1872-8057

ER -