16,17-Dihydro-17b-hydroxy isomitraphylline alkaloid as an inhibitor of DPP-IV, and its effect on incretin hormone and β-cell proliferation in diabetic rat.

Reduces levels of intact GLP-1 and inhibition of DPPIV augments levels of intact GLP-1 improves glycemic control in type 2 diabetes patients and diabetic animal model. Although, GLP-1 is known to stimulate insulin secretion, insulin biosynthesis and dose insulin gene transcription, augmented supplies of insulin for secretion. DHIM is an indole alkaloid, isolated from Mitragyna parvifolia. In the present in vitro study, we investigated the inhibitor activity of novel alkaloid on DPP IV. DHIM produced marked inhibition of DPP IV. Accordingly, we used 5, 10 and 20 μg DHIM alkaloids in DPPIV assay, and then found 18%, 56%, and 68% inhibition activity. In the present in vivo study, we examined the 16,17-dihydro-17b-hydroxy (DHIM) effect on neonatal Wistar albino rats treated with streptozotocin, an established model of type 2 diabetes. Diabetic rats, 8 weeks chronic administered with DHIM (100mg/kg) markedly reduced plasma glucose concentration, increased glucose tolerance in response to glucose loading. Consequently, GLP-1 and IL-10 levels were also significantly increased in treated diabetic rats. Despite, body weight was not found changed significantly; the insulin content and β-cell mass at 2 months were significantly increased by DHIM. Immunostaining and Confocal image of TUNEL assay showed that DHIM stimulates β-cell proliferation and reduced pancreatic cell apoptosis in diabetic treated rats. These results suggest that DHIM induces proliferation of pancreatic cells and increases the formation of β-cells.