Characterization of miR-218/322-Stxbp1 pathway in the process of insulin secretion

Ai, Zhihua; You, Zhiqing; Wan, Yong; Guo, Wei; Xiao, Jie; Jin, Xiaolan

doi:10.1530/jme-14-0305

Cited by 15 publications

(11 citation statements)

References 23 publications

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“…It is clear that rapid glucagon and insulin secretion is primarily regulated through autocrine factors, and endogenic miRNAs are involved in insulin synthesis and release [ 6 , 10 ]. Therefore, the aim of the present study was to identify the potential miRNAs that regulate glucagon secretion.…”

Section: Resultsmentioning

confidence: 99%

“…Generally, a reduction in blood glucose level promotes the release of glucagon from α cells [ 4 , 5 ], while high blood glucose boosts insulin release from β cells. Previous studies have been focused on the molecular mechanisms underlying insulin synthesis and release [ 6 , 7 ]; however, the biological process of glucagon secretion is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells

Zhang

Deng

et al. 2016

Oncotarget

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Glucagon, secreted from islet alpha cells, plays an important role in regulating glucose homeostasis; however, the molecular mechanism underlying this process is not fully understood. Previous studies have demonstrated that miRNAs are involved in the function of alpha cells. Glutamate promotes glucagon secretion by mediating the opening of Ca2+ channels. In this present, iGluR2 and iGluR3 levels were significantly increased in fasting-treated mouse islets. Additional studies showed that miR-124-3p simultaneously regulates the expression of iGluR2 and iGluR3 through the direct targeting of mRNA 3’UTR of these two genes. The miR-124-iGluRs pathway also contributed to the high level of glucagon secretion through long-term high glucose levels. Thus, a novel pathway comprising miRNA, glutamate and iGluRs has been demonstrated to regulate the biological process of glucagon release.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells

Zhang

Deng

et al. 2016

Oncotarget

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“…Here, the background cell is a transmission electron microscope (TEM) image of a human β‐cell. Listed are miRNAs involved in insulin biosynthesis and processing, glucose uptake and metabolism, electrical activity and Ca 2+ ‐influx and exocytosis of the insulin granules . RER, rough endoplasmatic reticulum; TGN, trans Golgi network; VDCC, voltage‐dependent Ca 2+ channel…”

Section: Insulin Production and Mirnasmentioning

confidence: 99%

“…Listed are miRNAs involved in insulin biosynthesis and processing, 13,27-35 glucose uptake and metabolism, [36][37][38][39][40] electrical activity and Ca 2+ -influx 41,42 and exocytosis of the insulin granules. [43][44][45][46][47][48][49][50] RER, rough endoplasmatic reticulum; TGN, trans Golgi network; VDCC, voltage-dependent Ca 2+ channel maintaining β-cell function. 53 Thus, miR-204 could be one of the key miRNAs whose increased expression contributes to the β-cell decompensation in T2D.…”

Section: Insulin Production and Mirnasmentioning

confidence: 99%

MicroRNAs in islet hormone secretion

Esguerra

Nagao

Ofori

et al. 2018

Diabetes Obesity Metabolism

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Pancreatic islet hormone secretion is central in the maintenance of blood glucose homeostasis. During development of hyperglycaemia, the β-cell is under pressure to release more insulin to compensate for increased insulin resistance. Failure of the β-cells to secrete enough insulin results in type 2 diabetes (T2D). MicroRNAs (miRNAs) are short non-coding RNA molecules suitable for rapid regulation of the changes in target gene expression needed in β-cell adaptations. Moreover, miRNAs are involved in the maintenance of α-cell and β-cell phenotypic identities via cell-specific, or cell-enriched expression. Although many of the abundant miRNAs are highly expressed in both cell types, recent research has focused on the role of miRNAs in β-cells. It has been shown that highly abundant miRNAs, such as miR-375, are involved in several cellular functions indispensable in maintaining β-cell phenotypic identity, almost acting as "housekeeping genes" in the context of hormone secretion. Despite the abundance and importance of miR-375, it has not been shown to be differentially expressed in T2D islets. On the contrary, the less abundant miRNAs such as miR-212/miR-132, miR-335, miR-130a/b and miR-152 are deregulated in T2D islets, wherein the latter three miRNAs were shown to play key roles in regulating β-cell metabolism. In this review, we focus on β-cell function and describe miRNAs involved in insulin biosynthesis and processing, glucose uptake and metabolism, electrical activity and Ca -influx and exocytosis of the insulin granules. We present current status on miRNA regulation in α-cells, and finally we discuss the involvement of miRNAs in β-cell dysfunction underlying T2D pathogenesis.

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“…There was notable downregulation in the deceased donor pancreases of MAF B 25 and ARX, 26 which are important for a cell identity. SYT13 27 and STXBP1, 28 which are important components of the b cell exocytotic machinery, were both downregulated. Also downregulated were the important b cell genes NKX6.1, a key transcription factor 29 ; ABCC8, the sulfonylurea receptor 30 ; and PAX6.…”

Section: Islet Cell Identity Genesmentioning

confidence: 99%

Evidence of stress in β cells obtained with laser capture microdissection from pancreases of brain dead donors

Ebrahimi

Jung

Dreyfuss

et al. 2017

Islets

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Isolated islets used for transplantation are known to be stressed, which can result from the circumstances of death, in particular brain death, the preservation of the pancreas with its warm and cold ischemia, from the trauma of the isolation process, and the complex events that occur during tissue culture. The current study focused upon the events that occur before the islet isolation procedure. Pancreases were obtained from brain dead donors (n = 7) with mean age 50 (11) and normal pancreatic tissue obtained at surgery done for pancreatic neoplasms (n = 7), mean age 69 (9). Frozen sections were subjected to laser capture microdissection (LCM) to obtain β-cell rich islet tissue, from which extracted RNA was analyzed with microarrays. Gene expression of the 2 groups was evaluated with differential expression analysis for genes and pathways. Marked changes were found in pathways concerned with endoplasmic reticulum stress with its unfolded protein response (UPR), apoptotic pathways and components of inflammation. In addition, there were changes in genes important for islet cell identity. These findings advance our understanding of why islets are stressed before transplantation, which may lead to strategies to reduce this stress and lead to better clinical outcomes.

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Characterization of miR-218/322-Stxbp1 pathway in the process of insulin secretion

Cited by 15 publications

References 23 publications

The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells

The microRNA-124-iGluR2/3 pathway regulates glucagon release from alpha cells

MicroRNAs in islet hormone secretion

Evidence of stress in β cells obtained with laser capture microdissection from pancreases of brain dead donors

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