Rosiglitazone protects INS-1E cells from human islet amyloid polypeptide toxicity

Human islet amyloid polypeptide (hIAPP or amylin) is a hormone co-secreted with insulin by pancreatic 8 -cells, and is the main component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes and may be involved in 8 -cell dysfunction and death, observed in this disease. Thus, counteracting islet amyloid toxicity represents a therapeutic approach to preserve 8 -cell mass and function. In this sense, thiazolidinediones (TZDs), as rosiglitazone, have shown protective effects against other harmful insults to 8 -cells. For this reason, we investigated whether rosiglitazone could protect 8 -cells from hIAPP-induced cell death and the underlying mechanisms mediating such effect. Here, we show that rosiglitazone improved the viability of hIAPP-exposed INS-1E cells. This benefit is not dependent on the insulin-degrading enzyme (IDE) since rosiglitazone did not modulate IDE protein content and activity. However, rosiglitazone inhibited hIAPP fibrillation and decreased hIAPP-induced expression of C/EBP homologous protein (CHOP) (CTL 100.0 & PLUSMN; 8.4; hIAPP 182.7 & PLUSMN; 19.1; hIAPP + RGZ 102.8 & PLUSMN; 9.5), activating transcription factor-4 (ATF4) (CTL 100.0 & PLUSMN; 3.1; hIAPP 234.9 & PLUSMN; 19.3; hIAPP + RGZ 129.6 & PLUSMN; 3.0) and phospho-eukaryotic initiation factor 2-alpha (p-eIF2a) (CTL 100.0 & PLUSMN; 31.1; hIAPP 234.1 & PLUSMN; 36.2; hIAPP + RGZ 150.4 & PLUSMN; 18.0). These findings suggest that TZDs treatment may be a promising approach to preserve 8 -cell mass and function by inhibiting islet amyloid formation and decreasing endoplasmic reticulum stress hIAPP-induced.

Automated summary

The study demonstrates that rosiglitazone can improve the viability of INS-1E cells exposed to hIAPP, independent of insulin-degrading enzyme (IDE) modulation. Rosiglitazone inhibited hIAPP fibrillation and reduced hIAPP-induced expression of CHOP, ATF4, and p-eIF2a, suggesting that TZDs treatment may be a promising approach to preserve β-cell mass and function.