Nerve conduction study and Fas mediated apoptosis of nerve cells in peripheral neuropathy in type 2 diabetes

ABSTRACT

Apoptosis may play a crucial role in the pathogenesis of late diabetic neuropathy. We determine the role of Fas mediated apoptosis in the aetiopathogenesis of diabetic neuropathy, by measurement of apoptosis markers, induction of apoptosis by Fas and/or serum and correlate the level of soluble Fas [marker of apoptosis] with the nerve conduction study. Furthermore, we elucidate the role of apoptosis inhibition in prevention of diabetic neuropathy by the Fas blocker [ZB4]. There was significant increase in the sFas serum level in diabetics with neuropathy as compared to the controls and diabetic patients without neuropathy [p < 0.005]. All parameters of the motor median nerve conduction study showed significant correlation with the serum sFas levels, especially the nerve conduction velocity [r=-0.60, p<0.01]. Cells treated with the serum of diabetic patients with neuropathy showed significantly higher percentages of early and late apoptosis [p < 0.05] compared to the negative control. A 500ng/mL Fas blocker [ZB4], antagonistic anti-Fas antibody caused significantly lower levels of early and late apoptosis [p < 0.025] compared to serum of diabetic patients with neuropathy treatment. In conclusion, Fas-mediated apoptosis of the neuronal cell line is responsible for the degradation of the neurons in patients with diabetic neuropathy and provides evidence for the involvement of the receptor pathway in Fas-mediated apoptosis of these cells. Thus, targeting and inhibiting Fas receptor offers an option for diabetic neuropathy therapy