Overexpressed beta cell CART increases insulin secretion in mouse models of insulin resistance and diabetes

Abels, Mia; Riva, Matteo; Shcherbina, Liliya; Fischer, Ann-Helen Thorén; Banke, Elin; Degerman, Eva; Lindqvist, Andreas; Wierup, Nils

doi:10.1016/j.peptides.2022.170747

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…First, we used the PubMed database [ 75 ] and characterized each of the 39 novel PAG-related DEGs of the tame and aggressive rats ( Table 2 ) by answering the question as to how under- or overexpression of their human orthologs can aggravate or alleviate ARDs [ 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , ...…”

Section: Resultsmentioning

confidence: 99%

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Shikhevich

Chadaeva

Khandaev

et al. 2023

IJMS

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Mainstream transcriptome profiling of susceptibility versus resistance to age-related diseases (ARDs) is focused on differentially expressed genes (DEGs) specific to gender, age, and pathogeneses. This approach fits in well with predictive, preventive, personalized, participatory medicine and helps understand how, why, when, and what ARDs one can develop depending on their genetic background. Within this mainstream paradigm, we wanted to find out whether the known ARD-linked DEGs available in PubMed can reveal a molecular marker that will serve the purpose in anyone’s any tissue at any time. We sequenced the periaqueductal gray (PAG) transcriptome of tame versus aggressive rats, identified rat-behavior-related DEGs, and compared them with their known homologous animal ARD-linked DEGs. This analysis yielded statistically significant correlations between behavior-related and ARD-susceptibility-related fold changes (log2 values) in the expression of these DEG homologs. We found principal components, PC1 and PC2, corresponding to the half-sum and the half-difference of these log2 values, respectively. With the DEGs linked to ARD susceptibility and ARD resistance in humans used as controls, we verified these principal components. This yielded only one statistically significant common molecular marker for ARDs: an excess of Fcγ receptor IIb suppressing immune cell hyperactivation.

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Section: Resultsmentioning

confidence: 99%

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Shikhevich

Chadaeva

Khandaev

et al. 2023

IJMS

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“…miR‐493‐5p and CARTPT shared eight base pairs, suggesting that miR‐493‐5p is a robust repressor of CARTPT. CARTPT, which stands for cocaine‐ and amphetamine‐regulated transcript prepropeptide, has been reported to be involved in diabetes, 30 Alzheimer's disease, 31 etc. Although Lu et al 32 reported that CARTPT is associated with mammary mucous carcinoma, the molecular mechanism has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Cancer‐associated fibroblasts promote tumor cell growth via miR‐493‐5p in intrahepatic cholangiocarcinoma

et al. 2022

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The association between tumor microenvironment (TME) and cancer‐associated fibroblasts (CAFs) in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. This study aimed to reveal whether specific microRNAs (miRNAs) in extracellular vesicles (EVs) derived from CAFs were involved in ICC progression. Conditioned medium (CM) and EVs in the CM of CAFs and normal fibroblasts (NFs) derived from ICC specimens were used to investigate the effects on tumor cell lines. miRNA microarray assay was used to examine the miRNAs of EVs derived from CAFs and NFs in ICC, and the effects of miR‐493‐5p on tumor cell lines were examined. Additionally, databases were used to identify miR‐493‐5p targets, and the relationship between prognosis of ICC patients and cocaine‐ and amphetamine‐regulated transcript propeptide (CARTPT), one of the targets of miR‐493‐5p, expression in ICC tissues was retrospectively analyzed. Compared with NF‐derived CM and EVs, CAF‐derived CM and EVs promoted cell lines in proliferation, scratch, migration, and invasion assays. miRNA microarray analysis revealed that miR‐493‐5p was significantly increased in CAF‐derived EVs compared to NF‐derived EVs. Tumor cell lines transfected with miR‐493‐5p were promoted in proliferation and scratch assays. Immunohistochemical staining was performed on 76 ICC specimens; both overall and recurrence‐free survival rates were significantly worse in the CARTPT‐negative group. Univariate and multivariate analyses showed that low CARTPT expression was an independent poor prognostic factor for overall and recurrence‐free survival. Overall, our data suggest that CAFs in the ICC TME suppress CARTPT in tumor cells and promote tumor cells via miR‐493‐5p in EVs.

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“… 29 In pancreatic beta cells CART is necessary for normal islet function and insulin secretion by glucose. 30 It induces the phosphorylation of CREB, MAPK, PKB and FoxO1 that are all key mediators of cell survival and proliferation, whereas it prevents pancreatic beta cell apoptosis induced by glucotoxicity. 31 Since no data exist regarding the expression of CART by the biliary epithelium and concerning its potential role in cholangiocytes proliferation, in the present research we aimed at assessing the expression/role of CART in the biliary epithelium and its possible role in biliary homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium

Casini,

Vivacqua,

Vaccaro

et al. 2023

Eur J Histochem

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Cholangiocytes, the epithelial cells that line the biliary tree, can proliferate under the stimulation of several factors through both autocrine and paracrine pathways. The cocaine-amphetamine-regulated-transcript (CART) peptide has several physiological functions, and it is widely expressed in several organs. CART increases the survival of hippocampal neurons by upregulating brain-derived neurotrophic factor (BDNF), whose expression has been correlated to the proliferation rate of cholangiocytes. In the present study, we aimed to evaluate the expression of CART and its role in modulating cholangiocyte proliferation in healthy and bile duct ligated (BDL) rats in vivo, as well as in cultured normal rat cholangiocytes (NRC) in vitro. Liver samples from both healthy and BDL (1 week) rats, were analyzed by immunohistochemistry and immunofluorescence for CART, CK19, TrkB and p75NTR BDNF receptors. PCNA staining was used to evaluate the proliferation of the cholangiocytes, whereas TUNEL assay was used to evaluate biliary apoptosis. NRC treated or not with CART were used to confirm the role of CART on cholangiocytes proliferation and the secretion of BDNF. Cholangiocytes proliferation, apoptosis, CART and TrkB expression were increased in BDL rats, compared to control rats. We found a higher expression of TrkB and p75NTR, which could be correlated with the proliferation rate of biliary tree during BDL. The in vitro study demonstrated increased BDNF secretion by NRC after treatment with CART compared with control cells. As previously reported, proliferating cholangiocytes acquire a neuroendocrine phenotype, modulated by several factors, including neurotrophins. Accordingly, CART may play a key role in the remodeling of biliary epithelium during cholestasis by modulating the secretion of BDNF.

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Overexpressed beta cell CART increases insulin secretion in mouse models of insulin resistance and diabetes

Cited by 5 publications

References 27 publications

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

Cancer‐associated fibroblasts promote tumor cell growth via miR‐493‐5p in intrahepatic cholangiocarcinoma

Expression and role of cocaine-amphetamine regulated transcript (CART) in the proliferation of biliary epithelium

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