Investigation of effect of humanin on cell viability in the model of experimental diabetic neuropathy

Diabetic neuropathy (DN) is a multifactorial disease that affects both central and peripheral nerves due to impaired glucose metabolism and can cause mitochondrial dysfunction. In addition, DN causes changes in the functions of dorsal root ganglia (DRG) neurons, which play a major role in the transport of nociceptive signals to the central nervous system. It is known that humanin, the first peptide discovered to originate from mitochondria, has antiapoptotic properties in neuropathy. However, it is not known how long-term humanin administration affects serum caspase 3 and caspase 9 levels in the in vivo model of DN. It is also not known how and through which pathway humanin affects cell viability in vitro model of DN. The aim of this thesis is to investigate the possible effects and mechanism of humanin on apoptosis and cell viability in in vivo and in vitro models of DN. In in vivo model of DN, humanin (4 mg/kg, i.p.) was administered for 15 days, 21 days after diabetes onset. Afterward, the serum caspase 3 and caspase 9 levels of the mice were measured. The in vitro model of DN was performed by exposing DKG neurons to high glucose (HG) (45 mmol/L) for 24 hours. Humanin was found to significantly reduce caspase 3 and caspase 9 levels in in vivo model of DN (p<0.05). In in vitro model of DN, it was determined that humanin (10 nM, 30 nM, 100 nM, and 300 nM) significantly increased cell viability in a dose-dependent manner and this effect was via JAK2/STAT3 pathway. As a result, it was shown for the first time in this thesis that humanin has a protective effect on cell viability in DN-dependent apoptotic processes and sensory nerve cells, and it exerts this effect through the JAK2/STAT3 pathway. The results of this study suggest that humanin may be a therapeutic target in DN resulting from diabetes, which is an important public health problem.