Development of Regulatory Subunit P85 Vaccination as a Novel Preventive Approach for Type 2 Diabetes Mellitus

Mahendra, Aditya I. 1 , Afifah, Yuri 1 , Indra, Rasjad M.2

1 2

Faculty of Medicine, Brawijaya University, Malang.

Department of Physiology, Brawijaya University, Malang.

Diabetes mellitus is a chronic metabolic disease with highest mortality and morbidity worldwide with 90-95% cases among them were type 2 diabetes mellitus (DM ) that caused by insulin resistance. The underlying mechanism to develop insulin resistance is remain enigmatic but recent studies suggested that obesity-induced overexpression of p85, regulatory subunit isoform of PI-3kinase, play an important role in mediating this process. Previous study showed that p85 antibody specifically bound with regulatory subunit p85 expressed in cell cytoplasm in vitro. This research aim at investigating whether vaccination using p85 had protective effect to prevent insulin resistance in type 2 DM . Rattus novergicus as animal models were divided into control group given normal diet and treatment groups given high fat diet and streptozotocin injection to develop type 2 DM . The treatment groups were injected by p85 100 L + CFAIFA 100 L, p85 100 L, and CFA-IFA 100 L solution. Vaccine were injected three times at two weeks interval. After 7 weeks all rats were sacrificed. Changes in body weight and visceral fat were recorded whereas serum level of blood glucose and advanced glycation end product (AGE) were analyzed using standard methods. The result showed that there was no difference in the means of diet intake among groups (p>0.05). Administration of p85 + CFA -IFA and p85 alone could significantly reduce the body weight and visceral fat compared to the positive control group (p < 0,05). M oreover, p85 + CFA-IFA also caused notable decrease in blood glucose level and AGE formation (p < 0,05). Bivariate analysis showed there were significant correlation between decrease in body weight and reduction of blood glucose level and AGE formation. These results suggest that p85 vaccination can effectively decrease body weight, blood glucose level and AGE formation related to the risk of type 2 DM . Thus, it shows a potential ability as novel preventive approach against type 2 DM . Keywords : type 2 diabetes mellitus, insulin resistance, obesity, p85