Correlations between Insulin Receptor Substrate-1 with Phosphoinositide 3-Kinase and P38 Mitogen-Activated Protein Kinase Levels after Treatment of Diabetic Rats with Puguntano (Curanga Fel-Terrae [Merr.]) Leaf Extract

BACKGROUND: Defects in post-receptor insulin signalling are the major cause of insulin resistance in type 2 diabetes mellitus (T2DM). AIM: This study aimed to investigate the correlations between insulin receptor substrate (IRS)-1 with phosphoinositide 3-kinase (PI3K) and p38 mitogen-activated protein kinase (MAPK) levels after puguntano (Curanga fel-terrae [Merr.]) leaf extract treatment in a rat model of T2DM. METHODS: A combination of high-fat diet-feeding (HFD) and multiple low dose intraperitoneal injections of streptozotocin was used to induced T2DM in 48 Wistar rats, which were then randomly divided into control and treatment groups (n = 24 per group). Puguntano leaf extract was administered to the treatment group once daily (200 mg/kg.bw) for 10 days. IRS-1, PI3K and p38 MAPK levels were measured in skeletal muscle using sandwich ELISAs in control group after becoming T2DM and in the treatment group after 10 days of puguntano treatment. Data were analysed using the Wilcoxon test and Spearman’s correlation. RESULTS: IRS-1, PI3K and p38 MAPK levels were significantly higher in the treatment group than in the control group. There were also significant positive correlations between IRS-1 with PI3K and p38 MAPK levels (r = 0.375, p = 0.035; r = 0.552, p = 0.003; respectively) after the treatment. CONCLUSION: This study demonstrated significant positive correlations between IRS-1 with PI3K and p38 MAPK levels after puguntano leaf extract treatment of T2DM rats.