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MicroRNAs in islet hormone secretion

Esguerra, Jonathan L.S. LU orcid ; Nagao, Mototsugu LU ; Ofori, Jones K. LU ; Wendt, Anna LU and Eliasson, Lena LU orcid (2018) In Diabetes, Obesity and Metabolism 20(Suppl 2). p.11-19
Abstract

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... (More)

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 Ca2+-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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
exocytosis, glucagon, insulin, metabolism, microRNA, α-cell, β-cell
in
Diabetes, Obesity and Metabolism
volume
20
issue
Suppl 2
pages
11 - 19
publisher
Wiley-Blackwell
external identifiers
  • pmid:30230181
  • scopus:85051806168
ISSN
1462-8902
DOI
10.1111/dom.13382
language
English
LU publication?
yes
id
3d493e47-23fa-416f-b3ab-c91d8f6f16ec
date added to LUP
2018-10-09 21:31:55
date last changed
2021-10-06 05:15:05
@article{3d493e47-23fa-416f-b3ab-c91d8f6f16ec,
  abstract     = {<p>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<sup>2+</sup>-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.</p>},
  author       = {Esguerra, Jonathan L.S. and Nagao, Mototsugu and Ofori, Jones K. and Wendt, Anna and Eliasson, Lena},
  issn         = {1462-8902},
  language     = {eng},
  month        = {09},
  number       = {Suppl 2},
  pages        = {11--19},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {MicroRNAs in islet hormone secretion},
  url          = {http://dx.doi.org/10.1111/dom.13382},
  doi          = {10.1111/dom.13382},
  volume       = {20},
  year         = {2018},
}