Elevated miR-130a/miR130b/miR-152 expression reduces intracellular ATP levels in the pancreatic beta cell
Ofori, Jones K. LU ; Salunkhe, Vishal A. LU ; Bagge, Annika LU ; Vishnu, Neelanjan LU ; Nagao, Mototsugu LU ; Mulder, Hindrik LU
; Wollheim, Claes B.
LU
; Eliasson, Lena
LU
and Esguerra, Jonathan L S
LU
(2017)
In Scientific Reports
7.
- Abstract
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats. We demonstrated negative regulatory effects of the three microRNAs on pyruvate dehydrogenase E1 alpha (PDHA1) and on glucokinase (GCK) proteins, which are both involved in ATP... (More)
MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats. We demonstrated negative regulatory effects of the three microRNAs on pyruvate dehydrogenase E1 alpha (PDHA1) and on glucokinase (GCK) proteins, which are both involved in ATP production. Consequently, we found both proteins to be downregulated in the Goto-Kakizaki rat islets, while GCK mRNA expression showed reduced trend in the islets of type-2 diabetes donors. Overexpression of any of the three microRNAs in the insulin-secreting INS-1 832/13 cell line resulted in altered dynamics of intracellular ATP/ADP ratio ultimately perturbing fundamental ATP-requiring beta cell processes such as glucose-stimulated insulin secretion, insulin biosynthesis and processing. The data further strengthen the wide-ranging influence of microRNAs in pancreatic beta cell function, and hence their potential as therapeutic targets in type-2 diabetes.
(Less)
- author
- Ofori, Jones K.
LU
; Salunkhe, Vishal A.
LU
; Bagge, Annika
LU
; Vishnu, Neelanjan
LU
; Nagao, Mototsugu
LU
; Mulder, Hindrik
LU
; Wollheim, Claes B.
LU
; Eliasson, Lena
LU
and Esguerra, Jonathan L S
LU
- organization
- publishing date
- 2017-03-23
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- article number
- 44986
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:28332581
- wos:000397184700001
- scopus:85016157333
- ISSN
- 2045-2322
- DOI
- 10.1038/srep44986
- language
- English
- LU publication?
- yes
- id
- a2474b98-4108-4d4a-b635-aa1245fa5ed6
- date added to LUP
- 2017-04-05 09:52:28
- date last changed
- 2024-07-07 15:31:06
@article{a2474b98-4108-4d4a-b635-aa1245fa5ed6,
abstract = {{<p>MicroRNAs have emerged as important players of gene regulation with significant impact in diverse disease processes. In type-2 diabetes, in which impaired insulin secretion is a major factor in disease progression, dysregulated microRNA expression in the insulin-secreting pancreatic beta cell has been widely-implicated. Here, we show that miR-130a-3p, miR-130b-3p, and miR-152-3p levels are elevated in the pancreatic islets of hyperglycaemic donors, corroborating previous findings about their upregulation in the islets of type-2 diabetes model Goto-Kakizaki rats. We demonstrated negative regulatory effects of the three microRNAs on pyruvate dehydrogenase E1 alpha (PDHA1) and on glucokinase (GCK) proteins, which are both involved in ATP production. Consequently, we found both proteins to be downregulated in the Goto-Kakizaki rat islets, while GCK mRNA expression showed reduced trend in the islets of type-2 diabetes donors. Overexpression of any of the three microRNAs in the insulin-secreting INS-1 832/13 cell line resulted in altered dynamics of intracellular ATP/ADP ratio ultimately perturbing fundamental ATP-requiring beta cell processes such as glucose-stimulated insulin secretion, insulin biosynthesis and processing. The data further strengthen the wide-ranging influence of microRNAs in pancreatic beta cell function, and hence their potential as therapeutic targets in type-2 diabetes.</p>}},
author = {{Ofori, Jones K. and Salunkhe, Vishal A. and Bagge, Annika and Vishnu, Neelanjan and Nagao, Mototsugu and Mulder, Hindrik and Wollheim, Claes B. and Eliasson, Lena and Esguerra, Jonathan L S}},
issn = {{2045-2322}},
language = {{eng}},
month = {{03}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Elevated miR-130a/miR130b/miR-152 expression reduces intracellular ATP levels in the pancreatic beta cell}},
url = {{http://dx.doi.org/10.1038/srep44986}},
doi = {{10.1038/srep44986}},
volume = {{7}},
year = {{2017}},
}