MiR‐335 overexpression impairs insulin secretion through defective priming of insulin vesicles

Salunkhe, Vishal A.; Ofori, Jones K.; Gandasi, Nikhil R.; Salö, Sofia; Hansson, S E; Andersson, Markus; Wendt, Anna; Barg, Sebastian; Esguerra, Jonathan L.S.; Eliasson, Lena

doi:10.14814/phy2.13493

Cited by 32 publications

(30 citation statements)

References 46 publications

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“…In the islets of lean T2D model GK‐rats, we found predominantly upregulated miRNAs whose collective targets are enriched for genes in the insulin exocytotic machinery . Specifically, we validated the direct targeting of Stxbp1 mRNA by miR‐335, and recently shown this miRNA to impair insulin secretion via defective priming of insulin vesicles . We have also found that miR‐130a/b and miR‐152, which are differentially expressed in T2D islets control ATP levels, something that will influence both insulin content and glucose stimulated insulin secretion .…”

Section: The Involvement Of Islet Mirnas In T2dmentioning

confidence: 66%

“…We have also found that miR‐130a/b and miR‐152, which are differentially expressed in T2D islets control ATP levels, something that will influence both insulin content and glucose stimulated insulin secretion . These miRNAs are not among the most highly expressed miRNAs in islets, and do not have the most evident effect sizes, yet they have important regulatory functions in β‐cell physiology by their regulation of metabolism and/or exocytosis …”

Section: The Involvement Of Islet Mirnas In T2dmentioning

confidence: 86%

“…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%

“…Moreover, the exocytotic gene Stxbp1 (Munc‐18a) is the direct target of miR‐335, one of the miRNAs upregulated in the well‐studied spontaneous T2D model GK‐rat . We recently showed reduced insulin granule priming in cells overexpressing miR‐335 The field of miRNA regulation of α‐cells is still in its infancy and we look forward to learning more about this fascinating field as research progresses.…”

Section: Role Of Mirnas In the Insulin Secretion Processmentioning

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%

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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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Section: The Involvement Of Islet Mirnas In T2dmentioning

confidence: 66%

Section: The Involvement Of Islet Mirnas In T2dmentioning

confidence: 86%

Section: Insulin Production and Mirnasmentioning

confidence: 99%

Section: Role Of Mirnas In the Insulin Secretion Processmentioning

confidence: 99%

Section: Insulin Production and Mirnasmentioning

confidence: 99%

See 3 more Smart Citations

MicroRNAs in islet hormone secretion

Esguerra

Nagao

Ofori

et al. 2018

Diabetes Obesity Metabolism

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Roles of Noncoding RNAs in Islet Biology

Guay

Jacovetti

Bayazit

et al. 2020

Comprehensive Physiology

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The discovery that most mammalian genome sequences are transcribed to RNA has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs, including microRNAs, Piwi-associated RNAs, small nucleolar RNAs, tRNAderived fragments, long non-coding RNAs and circular RNAs. While the involvement of microRNAs in islet function and in the etiology of diabetes is now well documented, there is emerging evidence indicating that other classes of non-coding RNAs are also participating in different aspects of islet physiology. The aim of this review will be to provide a comprehensive and updated view of the studies carried out in human samples and rodent models over the last 15 years on the role of non-coding RNAs in the control of α-and β-cell development and function and to highlight the recent discoveries in the field. We will not only describe the role of non-coding RNAs in the control of insulin and glucagon secretion but will also address the contribution of these regulatory molecules in the proliferation and survival of islet cells under physiological and pathological conditions. It is now well established that most cells release part of their non-coding RNAs inside small extracellular vesicles allowing the delivery of genetic material to neighboring or distantly located target cells. The role of these secreted RNAs in cell-to-cell communication between β-cells and other metabolic tissues as well as their potential use as diabetes biomarkers will be discussed.-Circulating non-coding RNAs represent promising biomarkers.

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Profiling of circulating serum exosomal microRNAs in elderly patients with infectious stress hyperglycaemia

Zeng

Lv³

et al. 2023

Clinical and Translational Dis

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BackgroundEarly diagnosis of hospitalized elderly patients with infectious stress hyperglycaemia (ISH) is clinically important, especially under the global coronavirus disease 2019 (COVID‐19) pandemic, as without timely prevention and effective treatment, it is likely to deteriorate into septic shock, thus worsening patient survival and complications. Moreover, cumulative studies have showed that patients with COVID‐19 are reported to have a greater prevalence of hyperglycaemia. However, the underlying mechanism remained unknown.Aim and methodSystematic screening of specific biomarkers of serum exosome‐derived microRNAs (sE‐miRNAs) from ISH patient has not yet been reported. In this study, sE‐miRNAs were derived from 10 elderly patients with ISH and 5 control patients with disease‐match without hyperglycaemia (non‐ISH). RNA sequencing identified that a total number of 49 sE‐miRNAs with differential expression between ISH and control group. Of which, top 22 miRNAs ranked by sensitivity × specificity were chosen for further research. Moreover, 7 out of 22 miRNAs that related to glucose metabolism or immune disorder were picked up for further validation in an independent cohort consisting of 52 participants (31 ISH and 21 non‐ISH).ResultA validation analysis revealed that three miRNAs (hsa‐miR‐21‐5p, hsa‐miR‐335‐5p and hsa‐miR‐28‐3p) were statistically up‐regulated in exosomes from ISH patients. In the validation cohort and discovery cohort, the AUC of three individual miRNAs ranged from 0.73 to 0.88. A logistic model combining three miRNAs achieved an AUC of 0.96. Besides, sE‐miRNAs‐based signatures effectively characterized patients' poor clinical outcome. Survival curve analysis showed that hsa‐miR‐335‐5p, hsa‐miR‐28‐3p but not hsa‐miR‐21‐5p, were significantly closely related to mortality, and the combination of these three miRNAs could also predict patients outcome (p < .05).ConclusionThis study depicted the circulating exosomal miRNAs change in ISH patient, which could be used as a promising biomarker to detect ISH at an early stage and predict patients clinical outcome.

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MiR‐335 overexpression impairs insulin secretion through defective priming of insulin vesicles

Cited by 32 publications

References 46 publications

MicroRNAs in islet hormone secretion

MicroRNAs in islet hormone secretion

Roles of Noncoding RNAs in Islet Biology

Profiling of circulating serum exosomal microRNAs in elderly patients with infectious stress hyperglycaemia

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