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

• Type 2 diabetes (T2D) is associated with low-grade inflammation. Here we investigate if the anti-inflammatorycytokine 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 T2Ddonors. Treatment with IL-4 for 48 h had no further effect on GSIS in these islets but significantly reduced secretionin ND islets. Acute treatment with IL-4 for 1 h had no effect on GSIS in ND islets which led us to suspect thatIL-4 affects a slow cellular mechanism such as gene transcription. IL-4 has been reported to regulate miR-378a-3pand, 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 samegene as peroxisome proliferator-activated receptor gamma co-activator 1 beta (PCG-1β) and we found that IL-4treatment showed a clear tendency to increased gene expression of PCG-1β. PCG-1β is a co-activator of peroxisomeproliferator-activated receptor gamma (PPARγ) and, the gene expression of PPARγ was also increased withIL-4 treatment. Our data suggests that the protective role of IL-4 on beta cell survival comes at the cost of loweredinsulin secretion, presumably involving the PPARγ-pathway.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Keyword

IL-4

Beta cell

Diabetes

Insulin secretion

microRNA

PPARγ

Publication and Content Type

art (subject category)

ref (subject category)