Efficacy and Mechanisms of Action of Oxytocin in NA/STZ-induced Diabetic Wistar Rats: Roles of Adipocytokines, PI3K/AKT, and AMPK Signaling Pathways.

BACKGROUND/AIM: Type 2 diabetes mellitus (T2DM) is a prevalent disorder characterized by an increased concentration of blood glucose and impaired insulin function. Throughout the course of the disease, β-cell function fails and insulin production decreases. Studying the molecular systems responsible for insulin production, release, and action is crucial for the management and treatment of the disease. Thus, this study aimed to scrutinize the therapeutic efficacies of oxytocin (OXT) on nicotinamide (NA)/streptozotocin (STZ)-induced diabetes in rats and elucidate the underlying mechanisms.

MATERIALS AND

METHODS

Wistar rats were supplied a single intraperitoneal (i.p.) dose of NA (120 mg/kg) 15 min before an i.p. injection of STZ (60 mg/kg) after fasting for 16 h. Ten days later, the diabetic rats were orally administered OXT every day for eight weeks at dose levels 0.5, 1, and 2 IU/kg.

RESULTS

The treatment of diabetic rats with OXT significantly improved oral glucose tolerance, serum insulin and C-peptide concentrations, and pancreatic islets' structure and function. Furthermore, the activities of liver glucose-6-phospatase and glycogen phosphorylase significantly decreased. OXT treatment also resulted in an increase in serum adiponectin levels, while the levels of serum resistin, omentin, vaspin, and free fatty acids significantly decreased. Additionally, OXT significantly alleviated the mRNA levels of components of the PI3K-AKT and AMPK signaling pathways as well as their effectors including PPARγ, insulin receptor (IR), IR substrates 1 and 2 (IRS1 & IRS2), PI3K, AKT, AMPK, and glucose transporter 4 (GLUT4) in visceral adipose tissues of diabetic rats.

CONCLUSION

OXT can exert antidiabetic effects and may be useful for developing multiple targeted therapeutic strategies for diabetes treatment. The effects may be mediated via improvement in β-cell function, insulin secretory response, and insulin sensitivity.