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Interleukin-4 reduces insulin secretion in human islets from healthy but not type-2 diabetic donors

Westholm, Efraim LU ; Edlund, Anna LU ; Karagiannopoulos, Alexandros LU orcid ; Wendt, Anna LU and Eliasson, Lena LU orcid (2023) In Biochemical and Biophysical Research Communications 649. p.87-92
Abstract
Type 2 diabetes (T2D) is associated with low-grade inflammation. Here we investigate if the anti-inflammatory
cytokine interleukin-4 (IL-4) affects glucose-stimulated insulin secretion (GSIS) in human islets from nondiabetic
(ND) and type-2 diabetic (T2D) donors. We first confirmed that GSIS is reduced in islets from T2D
donors. Treatment with IL-4 for 48 h had no further effect on GSIS in these islets but significantly reduced secretion
in ND islets. Acute treatment with IL-4 for 1 h had no effect on GSIS in ND islets which led us to suspect that
IL-4 affects a slow cellular mechanism such as gene transcription. IL-4 has been reported to regulate miR-378a-3p
and, indeed, we found that this microRNA was increased... (More)
Type 2 diabetes (T2D) is associated with low-grade inflammation. Here we investigate if the anti-inflammatory
cytokine interleukin-4 (IL-4) affects glucose-stimulated insulin secretion (GSIS) in human islets from nondiabetic
(ND) and type-2 diabetic (T2D) donors. We first confirmed that GSIS is reduced in islets from T2D
donors. Treatment with IL-4 for 48 h had no further effect on GSIS in these islets but significantly reduced secretion
in ND islets. Acute treatment with IL-4 for 1 h had no effect on GSIS in ND islets which led us to suspect that
IL-4 affects a slow cellular mechanism such as gene transcription. IL-4 has been reported to regulate miR-378a-3p
and, indeed, we found that this microRNA was increased with IL-4 treatment. However, overexpression of miR-
378a-3p in the human beta cell line EndoC-βH1 did not affect GSIS. MiR-378a-3p is transcribed from the same
gene as peroxisome proliferator-activated receptor gamma co-activator 1 beta (PCG-1β) and we found that IL-4
treatment showed a clear tendency to increased gene expression of PCG-1β. PCG-1β is a co-activator of peroxisome
proliferator-activated receptor gamma (PPARγ) and, the gene expression of PPARγ was also increased with
IL-4 treatment. Our data suggests that the protective role of IL-4 on beta cell survival comes at the cost of lowered
insulin secretion, presumably involving the PPARγ-pathway. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
IL-4, Beta cell, Diabetes, Insulin secretion, microRNA, PPARγ
in
Biochemical and Biophysical Research Communications
volume
649
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:85147596184
  • pmid:36758483
ISSN
1090-2104
DOI
10.1016/j.bbrc.2023.01.092
language
English
LU publication?
yes
id
ac8763d8-144e-4559-8172-5b8647ee87b5
date added to LUP
2023-01-31 16:40:56
date last changed
2023-05-04 03:03:22
@article{ac8763d8-144e-4559-8172-5b8647ee87b5,
  abstract     = {{Type 2 diabetes (T2D) is associated with low-grade inflammation. Here we investigate if the anti-inflammatory<br/>cytokine interleukin-4 (IL-4) affects glucose-stimulated insulin secretion (GSIS) in human islets from nondiabetic<br/>(ND) and type-2 diabetic (T2D) donors. We first confirmed that GSIS is reduced in islets from T2D<br/>donors. Treatment with IL-4 for 48 h had no further effect on GSIS in these islets but significantly reduced secretion<br/>in ND islets. Acute treatment with IL-4 for 1 h had no effect on GSIS in ND islets which led us to suspect that<br/>IL-4 affects a slow cellular mechanism such as gene transcription. IL-4 has been reported to regulate miR-378a-3p<br/>and, indeed, we found that this microRNA was increased with IL-4 treatment. However, overexpression of miR-<br/>378a-3p in the human beta cell line EndoC-βH1 did not affect GSIS. MiR-378a-3p is transcribed from the same<br/>gene as peroxisome proliferator-activated receptor gamma co-activator 1 beta (PCG-1β) and we found that IL-4<br/>treatment showed a clear tendency to increased gene expression of PCG-1β. PCG-1β is a co-activator of peroxisome<br/>proliferator-activated receptor gamma (PPARγ) and, the gene expression of PPARγ was also increased with<br/>IL-4 treatment. Our data suggests that the protective role of IL-4 on beta cell survival comes at the cost of lowered<br/>insulin secretion, presumably involving the PPARγ-pathway.}},
  author       = {{Westholm, Efraim and Edlund, Anna and Karagiannopoulos, Alexandros and Wendt, Anna and Eliasson, Lena}},
  issn         = {{1090-2104}},
  keywords     = {{IL-4; Beta cell; Diabetes; Insulin secretion; microRNA; PPARγ}},
  language     = {{eng}},
  month        = {{03}},
  pages        = {{87--92}},
  publisher    = {{Elsevier}},
  series       = {{Biochemical and Biophysical Research Communications}},
  title        = {{Interleukin-4 reduces insulin secretion in human islets from healthy but not type-2 diabetic donors}},
  url          = {{http://dx.doi.org/10.1016/j.bbrc.2023.01.092}},
  doi          = {{10.1016/j.bbrc.2023.01.092}},
  volume       = {{649}},
  year         = {{2023}},
}