Metformin (MET) is the preferred first-line treatment for patients with type 2 diabetes. However, the mechanism of diabetic peripheral neuropathy (DPN) is still unclear. To improve the oral utilization of metformin, a metformin nanoemulsion (MET-NE) was prepared to investigate its effects
on DPN and its underlying mechanism. In this study, a DPN model was established in Wistar rats induced by streptozotocin (STZ). The diabetic rats were randomly divided into four groups: the diabetic model group (DM group), the metformin tablet-treated group (MET group), the metformin nanoemulsion-treated
group (MET-NE group), and a normal control group consisting of five normal Wistar rats. All groups were administered the treatment orally for a period of 10 weeks. The findings of the study demonstrated that both MET and MET-NE significantly reduced blood glucose levels, glycated serum protein
levels, food intake, and water intake in DM rats. It was also observed that MET-NE was more effective than MET in reducing blood glucose levels. Additionally, both MET and MET-NE treatments significantly increased the motor nerve conduction velocity (MNCV), sensory nerve conduction velocity
(SNCV), and sensory nerve action potential (SNAP) amplitude in DM rats. Furthermore, these treatments improved mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL), resulting in a reduced sensitivity to pain stimuli. Moreover, both MET and MET-NE treatments promoted the
phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) proteins, as well as increased the activity of autophagic proteins in the sciatic nerve. However, no significant differences were observed between MET and MET-NE treatments in terms of these effects. In
conclusion, the MET-NE demonstrated a rapid decrease in blood glucose levels and improved glucose tolerance and metabolism, which was found to be superior to MET. Furthermore, MET-NE significantly improved the neurophysiological function and sciatic nerve pain threshold in DPN rats. These
beneficial effects may be attributed to the regulation of AMPK-mediated autophagy by MET-NE.
