Anti-diabetic effects of ifenprodil, A selective nmda-GLUN2B receptor antagonist, in TYPE-1 diabetic mice

N-methyl-D aspartate (NMDA) receptors, expressed in glutamatergic synapses of the central nervous system, have important subunit specific roles in the critical physiologic processes such as synaptic transmission, neuronal plasticity, and excitotoxicity. It has previously been reported that deletion of GluN2B (a subunit of NMDA receptors) from AgRP neurons leads to full correction of hyperglycemia in diabetic ob/ob mice, suggesting that GluN2B subunit may have anti-diabetic effects. Therefore, it was hypothesized that ifenprodil, a highly selective GluN2B antagonist, can have anti-diabetic effects in type-1 diabetic mice. A total of 26 BALB/c adult mice (6-8 weeks old) were used throughout the experimental period. Type-1 diabetes was induced by intraperitoneal streptozotocin administration (150 mg/kg). After inducing diabetes, different doses of ifenprodil (250 and 500 nM/day) were administered subcutaneously via osmotic mini-pump for 14 days. Daily body weight, food intake, and glucose levels were recorded throughout the experiment. At the end of the experiment, serum samples were decanted to measure glucagon and leptin levels after blood samples were collected by decapitation under deep anesthesia. The obtained data show that ifenprodil (500 nM/day) does not have effects on body weight and food intake (P>0.05), but it has glucose-lowering effects (P<0.001). In addition, It was found that both doses (250 and 500 nM/day) of ifenprodil entirely normalized glucagon levels. The findings indicate that ifenprodil may have glucose-lowering effects via glucagon, independently of food intake in type-1 diabetic mice.