Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The T-type calcium channel CaV3.2 regulates insulin secretion in the pancreatic β-cell

Barghouth, Mohammad LU ; Ye, Yingying LU ; Karagiannopoulos, Alexandros LU orcid ; Ma, Yunhan LU ; Cowan, Elaine LU orcid ; Wu, Rui LU ; Eliasson, Lena LU orcid ; Renström, Erik LU ; Luan, Cheng LU and Zhang, Enming LU (2022) In Cell Calcium 108.
Abstract

Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic β-cells and contributes to the development of type-2 diabetes (T2D). The role of the low-voltage gated T-type CaV channels in β-cells remains obscure. Here we have measured the global expression of T-type CaV3.2 channels in human islets and found that gene expression of CACNA1H, encoding CaV3.2, is negatively correlated with HbA1c in human donors, and positively correlated with islet insulin gene expression as well as secretion capacity in isolated human islets. Silencing or pharmacological blockade of CaV3.2 attenuates glucose-stimulated cytosolic Ca2+ signaling, membrane potential, and insulin release. Moreover, the... (More)

Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic β-cells and contributes to the development of type-2 diabetes (T2D). The role of the low-voltage gated T-type CaV channels in β-cells remains obscure. Here we have measured the global expression of T-type CaV3.2 channels in human islets and found that gene expression of CACNA1H, encoding CaV3.2, is negatively correlated with HbA1c in human donors, and positively correlated with islet insulin gene expression as well as secretion capacity in isolated human islets. Silencing or pharmacological blockade of CaV3.2 attenuates glucose-stimulated cytosolic Ca2+ signaling, membrane potential, and insulin release. Moreover, the endoplasmic reticulum (ER) Ca2+ store depletion is also impaired in CaV3.2-silenced β-cells. The linkage between T-type (CaV3.2) and L-type CaV channels is further identified by the finding that the intracellular Ca2+ signaling conducted by CaV3.2 is highly dependent on the activation of L-type CaV channels. In addition, CACNA1H expression is significantly associated with the islet predominant L-type CACNA1C (CaV1.2) and CACNA1D (CaV1.3) genes in human pancreatic islets. In conclusion, our data suggest the essential functions of the T-type CaV3.2 subunit as a mediator of β-cell Ca2+ signaling and membrane potential needed for insulin secretion, and in connection with L-type CaV channels.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cell Calcium
volume
108
article number
102669
publisher
Elsevier
external identifiers
  • scopus:85141268230
  • pmid:36347081
ISSN
0143-4160
DOI
10.1016/j.ceca.2022.102669
language
English
LU publication?
yes
id
ce7730f8-4478-4c44-ae1f-4764ea1b4a33
date added to LUP
2022-11-23 11:42:45
date last changed
2025-03-07 13:48:15
@article{ce7730f8-4478-4c44-ae1f-4764ea1b4a33,
  abstract     = {{<p>Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic β-cells and contributes to the development of type-2 diabetes (T2D). The role of the low-voltage gated T-type CaV channels in β-cells remains obscure. Here we have measured the global expression of T-type CaV3.2 channels in human islets and found that gene expression of CACNA1H, encoding CaV3.2, is negatively correlated with HbA1c in human donors, and positively correlated with islet insulin gene expression as well as secretion capacity in isolated human islets. Silencing or pharmacological blockade of CaV3.2 attenuates glucose-stimulated cytosolic Ca2+ signaling, membrane potential, and insulin release. Moreover, the endoplasmic reticulum (ER) Ca2+ store depletion is also impaired in CaV3.2-silenced β-cells. The linkage between T-type (CaV3.2) and L-type CaV channels is further identified by the finding that the intracellular Ca2+ signaling conducted by CaV3.2 is highly dependent on the activation of L-type CaV channels. In addition, CACNA1H expression is significantly associated with the islet predominant L-type CACNA1C (CaV1.2) and CACNA1D (CaV1.3) genes in human pancreatic islets. In conclusion, our data suggest the essential functions of the T-type CaV3.2 subunit as a mediator of β-cell Ca2+ signaling and membrane potential needed for insulin secretion, and in connection with L-type CaV channels.</p>}},
  author       = {{Barghouth, Mohammad and Ye, Yingying and Karagiannopoulos, Alexandros and Ma, Yunhan and Cowan, Elaine and Wu, Rui and Eliasson, Lena and Renström, Erik and Luan, Cheng and Zhang, Enming}},
  issn         = {{0143-4160}},
  language     = {{eng}},
  month        = {{10}},
  publisher    = {{Elsevier}},
  series       = {{Cell Calcium}},
  title        = {{The T-type calcium channel CaV3.2 regulates insulin secretion in the pancreatic β-cell}},
  url          = {{http://dx.doi.org/10.1016/j.ceca.2022.102669}},
  doi          = {{10.1016/j.ceca.2022.102669}},
  volume       = {{108}},
  year         = {{2022}},
}