Interleukin-4 reduces insulin secretion in human islets from healthy but not type-2 diabetic donors
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/ac8763d8-144e-4559-8172-5b8647ee87b5
- author
- Westholm, Efraim LU ; Edlund, Anna LU ; Karagiannopoulos, Alexandros LU ; Wendt, Anna LU and Eliasson, Lena LU
- organization
- publishing date
- 2023-03-15
- 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}}, }