Cocaine- and Amphetamine-regulated Transcript (CART) Protects Beta Cells against Glucotoxicity and Increases Cell Proliferation

Sathanoori, Ramasri; Olde, Björn; Erlinge, David; Göransson, Olga; Wierup, Nils

doi:10.1074/jbc.m112.437145

Cited by 30 publications

(23 citation statements)

References 63 publications

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“…Interestingly, in the presence of GLP-1 or cyclic AMPproducing agents, CART 55-102 consistently amplifies insulin secretion from rodent islets in a protein kinase A (PKA)-dependent manner [7,21,24]. CART 55-102 also protects beta cells against glucotoxicity and promotes survival and induces proliferation of beta cells [17]. In addition, it inhibits glucagon secretion of human and mouse islets at low glucose [7], and modestly inhibits somatostatin secretion from rat islets [17,24].…”

Section: Cart Expressionmentioning

confidence: 99%

“…CART 55-102 also protects beta cells against glucotoxicity and promotes survival and induces proliferation of beta cells [17]. In addition, it inhibits glucagon secretion of human and mouse islets at low glucose [7], and modestly inhibits somatostatin secretion from rat islets [17,24].…”

Section: Cart Expressionmentioning

confidence: 99%

“…Other studies have reported that CART increases cyclic AMP levels, which rather points to the involvement of G s proteins. CART was also found to induce phosphorylation of cyclic AMP-response element-binding protein (CREB), insulin receptor substrate protein (IRS), protein kinase B (PKB), forkhead box protein O1 (FoxO1), p44/42-mitogen-activated protein kinase (p44/42 MAPK, also known as extracellular signal-regulated kinase [ERK1/2]) and p90 ribosomal S6 kinase (p90RSK) in INS-1 cells or hypothalamic neurons [8,17]. The possibility that multiple CART receptor subtypes exist is strengthened by the observations that CART 55-102 and CART 62-102 display different potencies in some studies [8].…”

Section: Synthesis and Processing Of Cart Peptidesmentioning

confidence: 99%

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Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

Gilon

2016

Diabetologia

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Section: Cart Expressionmentioning

confidence: 99%

Section: Cart Expressionmentioning

confidence: 99%

Section: Synthesis and Processing Of Cart Peptidesmentioning

confidence: 99%

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Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

Gilon

2016

Diabetologia

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“…We have previously shown that addition of exogenous CART protects against glucotoxicity-induced beta-cell death (Sathanoori et al, 2013). To rule out that the observed effects of CART KD were secondary to reduced cell viability, we next assessed whether silencing of CART would influence beta-cell survival using the ApoTox-Glo Triplex assay.…”

Section: Cart Silencing Induces Beta-cell Apoptosis In Ins-1 (832/13)mentioning

confidence: 99%

“…Furthermore, administration of exogenous CART inhibits glucagon secretion in human and rodent islets as well as in vivo in mice due to reduced alpha-cell exocytosis (Abels et al, 2016). Furthermore, exogenous CART protects beta-cells against glucotoxicity-induced cell death in vitro in INS-1 (832/13) beta-cells Abbreviations: alpha-KIC, alpha-ketoisocaproate; CART, cocaine-and amphetamine-regulated transcript; CARTPT, human gene encoding CART; FCCP, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; GSIS, glucose-stimulated insulin secretion; KD, knock-down; OM, oligomycin; RRP, ready releasable pool.and rat islets (Sathanoori et al, 2013). In addition, endogenous beta-cell CART is upregulated in T2D patients as well as in several rodent models of T2D (Abels et al, 2016;, likely as a homeostatic response attempting to overcome hyperglycemia.…”

Section: Introductionmentioning

confidence: 99%

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

Shcherbina

Edlund

Esguerra

et al. 2017

Molecular and Cellular Endocrinology

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a b s t r a c tImpaired beta-cell function is key to the development of type 2 diabetes. Cocaine-and amphetamineregulated 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.

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Downregulation of Long Noncoding RNA Meg3 Affects Insulin Synthesis and Secretion in Mouse Pancreatic Beta Cells

You

Wang

Yin

et al. 2015

Journal Cellular Physiology

135

108

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Increasing evidence indicates that long noncoding RNAs (lncRNAs) are involved in diverse biological process. Mouse maternal expressed gene 3 (Meg3) is an imprinted gene and essential for development. Here, we explored the relationship between Meg3 and the function of mouse beta cells in vitro and in vivo. Real-time PCR analyses revealed that Meg3 was more abundantly expressed in Balb/c mouse islets than exocrine glands. Moreover, the expression of Meg3 in islets was decreased in T1DM (NOD female mice) and T2DM (db/db mice) models. Meg3 expression was modulated dynamically by glucose in Min6 cells and isolated mouse islets. The function role of Meg3 was investigated in Min6 cells and normal mouse by knockdown of Meg3 using small interfering RNA. After suppression of Meg3 expression in vitro, insulin synthesis and secretion were impaired and the rate of beta cells apoptosis was increased. Moreover, knockdown of Meg3 in vivo led to the impaired glucose tolerance and decreased insulin secretion, consisted with the reduction of insulin positive cells areas by immunochemistry assays. Notably, islets from Meg3 interference groups showed significant decrease of Pdx-1 and MafA expression in mRNA and protein levels. These results indicate that Meg3 may function as a new regulator of maintaining beta cells identity via affecting insulin production and cell apoptosis. J. Cell. Physiol. 231: 852-862, 2016. © 2015 Wiley Periodicals, Inc.

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Cocaine- and Amphetamine-regulated Transcript (CART) Protects Beta Cells against Glucotoxicity and Increases Cell Proliferation

Cited by 30 publications

References 63 publications

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

Cocaine- and amphetamine-regulated transcript: a novel regulator of energy homeostasis expressed in a subpopulation of pancreatic islet cells

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

Downregulation of Long Noncoding RNA Meg3 Affects Insulin Synthesis and Secretion in Mouse Pancreatic Beta Cells

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