Islet β cell: An endocrine cell secreting miRNAs

Zhang, Aisen; Li, Dameng; Liu, Yucheng; Li, Jing; Zhang, Yujing; Zhang, Chenyu

doi:10.1016/j.bbrc.2017.12.028

Cited by 35 publications

(41 citation statements)

References 27 publications

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“…Here, we demonstrate that pancreatic islets and beta cells export miRNAs, specifically miR-375-3p, to HDL and report key insights into processes that regulate export. Remarkably, contrary to exosomes in which miR-375-3p export was increased under cellular conditions that promote with insulin secretion 16 , we found that beta cell miR-375-3p export to HDL is suppressed by these same mechanisms that promote insulin secretion. Multiple conditions that stimulate insulin secretion from pancreatic beta cells - high glucose, tolbutamide, and persistent membrane depolarization - inhibited miRNA export to HDL.…”

Section: Introductioncontrasting

confidence: 80%

“…Extracellular miRNAs are also detected in plasma, where they are protected from RNase digestion by protein and/or lipid complexes 8,14,15 . Recently, miR-375-3p was also found to be released from beta cells in exosomes 16 , suggesting that miR-375-3p may have both cellular and extracellular roles. Nevertheless, extracellular miR-375-3p is not limited to just exosomes, as we have previously reported that HDL also transport miR-375-3p 8 .…”

Section: Introductionmentioning

confidence: 99%

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Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion

Sedgeman

Beysen

Solano

et al. 2019

Sci Rep

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Extracellular microRNAs (miRNAs) are a new class of biomarkers for cellular phenotypes and disease, and are bioactive signals within intercellular communication networks. Previously, we reported that miRNAs are secreted from macrophage to high-density lipoproteins (HDL) and delivered to recipient cells to regulate gene expression. Despite the potential importance of HDL-miRNAs, regulation of HDL-miRNA export from cells has not been fully studied. Here, we report that pancreatic islets and beta cells abundantly export miR-375-3p to HDL and this process is inhibited by cellular mechanisms that promote insulin secretion. Small RNA sequencing and PCR approaches were used to quantify beta cell miRNA export to HDL. Strikingly, high glucose conditions were found to inhibit HDL-miR-375-3p export, which was dependent on extracellular calcium. Likewise, stimulation of cAMP was found to repress HDL-miR-375-3p export. Furthermore, we found that beta cell ATP-sensitive potassium channel (K ATP ) channels are required for HDL-miRNA export as chemical inhibition (tolbutamide) and global genetic knockout ( Abcc8 −/− ) approaches inhibited HDL-miR-375-3p export. This process is not likely associated with cholesterol flux, as gain-of-function and loss-of-function studies for cholesterol transporters failed to alter HDL-miR-375-3p export. In conclusion, results support that pancreatic beta cells export miR-375-3p to HDL and this process is inversely regulated to insulin secretion.

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Section: Introductioncontrasting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion

Sedgeman

Beysen

Solano

et al. 2019

Sci Rep

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“…Many miRNAs were found to be predominantly present in MIN6 cells compared with the exosomes, as shown by the miRNA-seq data (Supplementary Figure S4 and Table S4). For example, miR-375-5p was enriched in MIN6 cells compared with the MIN6-derived exosomes, which is contradictory to a previous report [44]. The variability could be a consequence of the different MIN6 culture conditions and exosome isolation methods used [45] in the two studies.…”

Section: Identification Of the Mirna Profile Of The Min6-derived Exoscontrasting

confidence: 83%

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

Mandal

et al. 2020

Biomedicines

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Diabetes is a concerning health malady worldwide. Islet or pancreas transplantation is the only long-term treatment available; however, the scarcity of transplantable tissues hampers this approach. Therefore, new cell sources and differentiation approaches are required. Apart from the genetic- and small molecule-based approaches, exosomes could induce cellular differentiation by means of their cargo, including miRNA. We developed a chemical-based protocol to differentiate mouse embryonic fibroblasts (MEFs) into β-like cells and employed mouse insulinoma (MIN6)-derived exosomes in the presence or absence of specific small molecules to encourage their differentiation into β-like cells. The differentiated β-like cells were functional and expressed pancreatic genes such as Pdx1, Nkx6.1, and insulin 1 and 2. We found that the exosome plus small molecule combination differentiated the MEFs most efficiently. Using miRNA-sequencing, we identified miR-127 and miR-709, and found that individually and in combination, the miRNAs differentiated MEFs into β-like cells similar to the exosome treatment. We also confirmed that exocrine cells can be differentiated into β-like cells by exosomes and the exosome-identified miRNAs. A new differentiation approach based on the use of exosome-identified miRNAs could help people afflicted with diabetes

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“…Pancreatic β cells secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. It has been found that islet cells can secrete regulatory non-coding RNA [20], but whether circulating lncRNAs has function on target tissue has not been fully clarified yet. Therefore, identification of novel lncRNA for glucose metabolism based upon expression pattern in human circulation and effect on maintenance islet β-cell function would be very valuable.…”

Section: Introductionmentioning

confidence: 99%

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

Ruan¹,

Lin²,

Ma³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The islet is an important endocrine organ to secrete insulin to regulate the metabolism of glucose and maintain the stability of blood glucose. Long noncoding RNAs (lncRNAs) are involved in a variety of biological functions and play key roles in many diseases, including type 2 diabetes (T2D). The aim of this study was to determine whether lncRNA-p3134 is associated with glucose metabolism and insulin signaling in pancreatic β cells. Methods: LncRNA microarray technology was used to identify the differentially expressed circulating lncRNAs in T2D patients. RT-PCR analyses were performed to determine the expression of lncRNA-p3134 in 30 pairs of diabetic and non-diabetic patients. The correlation of lncRNA-p3134 to clinical data from T2D patients was analyzed. LncRNA-p3134 was overexpressed in Min6 cells and db/db mice by adenovirus-mediated technology. CCK-8, TUNEL, Western blot, glucose-stimulated insulin secretion (GSIS), ELISAs and immunochemistry were performed to determine the effect of lncRNA-p3134 on proliferation, apoptosis and insulin secretion both in vitro and vivo. Results: The circulating level of lncRNA-p3134 was higher in diabetic patients than in non-diabetic controls and was correlated with fasting blood glucose and HOMA-β levels. The lncRNA-p3134 had risen by 4 times in serum exosomes but nearly unchanged in exosome-free samples. The secretion of lncRNA-p3134 was dynamically modulated by glucose in both Min6 cells and isolated mouse islet cells. LncRNA-p3134 positively regulate GSIS through promoting of key regulators (Pdx-1, MafA, GLUT2 and Tcf7l2) in β cells. In addition, the overexpression of lncRNA-p3134 resulted in a decreased apoptosis ratio and partially reversed the glucotoxicity effects on GSIS function in Min6 cells. The restoration of insulin synthesis and secretion the increase of the insulin positive cells areas by upregulation of lncRNA-p3134 in db/db mice confirmed the compensatory role of lncRNA-p3134 to preserve β-cell function. Furthermore, a protective effect of lncRNA-p3134 on GSIS by positive modulation of PI3K/Akt/mTOR signaling was also confirmed. After blocking the PI3K/AKT signals with their specific inhibitor, the effect of overexpressed lncRNA-p3134 on insulin secretion was obviously attenuated. Conclusion: Taken together, the results of this study provide new insights into lncRNA-p3134 regulation in pancreatic β cells and provide a better understanding of novel mechanism of glucose homeostasis.

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Islet β cell: An endocrine cell secreting miRNAs

Cited by 35 publications

References 27 publications

Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion

Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion

Exosome-Mediated Differentiation of Mouse Embryonic Fibroblasts and Exocrine Cells into β-Like Cells and the Identification of Key miRNAs for Differentiation

Circulating LncRNAs Analysis in Patients with Type 2 Diabetes Reveals Novel Genes Influencing Glucose Metabolism and Islet β-Cell Function

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