Effects of MCC950 on lipid profiles, glycemic control, and sympathetic dysfunction in a streptozotocin-induced type 1 diabetic rat model.

AIM: To evaluate the effects of MCC950, a selective NLRP3 inflammasome inhibitor, on glycemic control, lipid profiles, and sympathetic dysfunction in a streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) rat model.

METHODS

Male Wistar rats were rendered diabetic by intraperitoneal injection of STZ (50 mg/kg). T1DM induction was confirmed by persistent hyperglycemia, reduced serum C-peptide, and pancreatic histopathological changes. Diabetic cardiac autonomic neuropathy was established by elevated serum noradrenaline (NA) before treatment. Diabetic rats subsequently received MCC950, insulin, or normal saline for four weeks. Fasting blood glucose, serum lipid profiles, C-peptide, pancreatic histology, and serum NA were evaluated before and after treatment.

RESULTS

MCC950-treated rats showed significantly reduced fasting blood glucose, total cholesterol, triglycerides, and LDL-cholesterol (all P<0.0001) levels compared with untreated diabetic rats, while HDL levels remained unchanged, which suggests an improvement in diabetes-associated dyslipidemia. MCC950 treatment also partially restored C-peptide concentrations, improved pancreatic histology, and reduced serum NA levels.

CONCLUSION

These findings suggest that NLRP3 inflammasome inhibition may improve metabolic disturbances associated with experimental T1DM. Further studies incorporating direct functional assessments of cardiac autonomic function are required to determine its role in diabetic cardiac autonomic neuropathy.