engleski

Toxicity of amylin from sera of NIDDM patients on isolated islet cells

Diabetes type II is accompanied by an elevated serum amylin. This paptide was shown to be cytotoxic to rat insulinoma islet beta-cells in tissue culture, through a mechanism which includes DNA damage and apoptosis. We have investigated the ability of diabetic patients sera to cause beta-cell death by a similar mechanism. Islets of Langerhans were isolated from rat pancreas by collagenase digestion and subsequently treated with sera of type II diabetic patients by incubation for 48 hours at 22oC. Viable cell count and nucleus fragmentation was determined by propidium iodide staining and fluorescent microscopy. Isolated rat Langerhans islets treated with sera from diabetic patients with hyperinsulinemia, have shown reduced viability of beta-cells, and morphological characteristics of apoptotic process. DNA fragmentation in islet beta-cells was also demonstrated. Control human sera, even at higher concentrations, did not cause the same effect. These findings identify DNA as an early target of "amylin" present in sera of diabetes type II patients with hyperglycaemia and hyperinsulinemia. Amylin from sera of diabetes type II patients is a likely candidate for a factor which enhances nucleus fragmentation, apoptosis and reduction of islet beta-cell population in vivo.

diabetes; Langerhans islets; sera; apoptosis; collagenase

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