Research and Development the Anti-Insulin Resistance Lead Compounds (I-III)

Elevation of free fatty acids plays an important role in obesity-induced insulin resistance, fatty liver disease, and type 2 diabetes mellitus. The patients with type 2 diabetes mellitus are accompanied with hyperglycemia result from reduced glucose uptake by adipose tissue and increased production of glucose by hepatocyte resistant to insulin action. Meanwhile, gluconeogenesis which is mainly controlled via the transcriptional regulation of hepatic phosphenolpyruvate carboxykinase (PEPCK) and glucose-6- phosphatase (G6Pase) acts a crucial role for the onset of hyperglycemia in diabetes, and also serves as an important index for evaluating the hepatic insulin resistance. Therefore, we will measure the mRNA levels of PEPCK and G6Pase in hepatocytes as an indication how the crude extracts or compounds attenuate hepatic insulin resistance. In the preliminary results, the insulin resistance is reduced by the methanolic extract of herbs at 10 μg/ml in AML12 cell hepatic insulin resistance test. We found the extracts of Achillea millefolium, Euphorbia formosana Hayata and Wikstroemia indica C.A. Meyer showed significantly inhibitory activities on G6Pase and PEPCK mRNA expression compared control with inhibitory rates of 96 %, 77%, 88% and 86 %, 63 %, 75 %, respectively. This study aims to look for anti-insulin resistance principles from A. millefolium (the first year), E. formosana Hayata (the second year) and W. indica C.A. Meyer (the third year) by virtue of bioassay-directed isolation and structural elucidation. The results could provide evidences for the chemotaxonomy of these three plants and bioactive principles in AML12 cell hepatic insulin resistance test.

Project ID:PC10207-0333
External Project ID:NSC102-2320-B182-013