Therapeutic potential of spexin in diabetic neuropathy: Insights from in vitro and in vivo models

The present study investigated the therapeutic potential of spexin (SPX) on both in vitro and in vivo models of diabetic neuropathy (DN). A total of 40 male BALB/c mice were randomly allocated into four experimental groups (n = 10 per group): a normoglycaemic control, an untreated DN group and two SPX treatment groups (DN+SPX-12.5 and DN+SPX-25). To induce the diabetic state, subjects received a single intraperitoneal (i.p.) injection of streptozotocin (STZ) at a dosage of 150 mg/kg. Following the establishment of DN, the treatment groups were administered SPX (12.5 or 25 µg/kg/day) via i.p. injection for 15 consecutive days, whereas the untreated DN group received an equivalent volume of saline vehicle. Thermal hyperalgesia and mechanical allodynia were subsequently evaluated utilizing the hot plate, tail-flick and electronic von Frey behavioural paradigms. in vitro assays demonstrated that SPX administration significantly restored the viability of high glucose-exposed dorsal root ganglion cells, while in vivo assessments revealed a marked attenuation of mechanical allodynia and thermal hyperalgesia in SPX-treated diabetic mice. Furthermore, SPX exhibited profound antioxidant and immunomodulatory properties by mitigating systemic oxidative stress and pro-inflammatory cytokine responses, concomitantly preserving the structural integrity of the pancreatic islets. Taken together, these findings provide compelling evidence that SPX confers neuroprotective benefits in STZ-induced DN through the modulation of oxidative stress, neuroinflammation and nociceptive sensitization, thereby highlighting its potential as a novel therapeutic agent for diabetic microvascular complications.