The extracts of small-leaved kudingcha as potential modulators of β-cells for the therapy of type 2 diabetes mellitus

Small-leaved Kudingcha (SLK), a unique variety of tea, has blood sugar-lowering effect. However, the underlying molecular mechanisms of lowering blood sugar is still unclear. Here, the crude extract of SLK and its four fractions of petroleum ether (SLK-PE), ethyl acetate (SLK-EA), n-butanol (SLK-NA), and water (SLK-WA) were prepared and analyzed by Liquid Chromatography-Mass spectrometry/Mass spectrometry. The findings revealed that SLK-PE and SLK-NA ameliorated polydipsia, polyphagia, and polyuria in T2DM mice, as well as serum biochemical indicators. We found that SLK-PE and SLK-NA could enhance blood sugar regulation ability and improve the degree of islet cells damage by upregulating the relative protein levels of p-PI3K/PI3K and p-AKT/AKT ratios, as well as Glut4, Nrf2, INS, SIRT1 and PGC-1α, while downregulating the expression levels of Keap-1, FoXO1, GSK3β, and GCG. Cellular experiment results further demonstrated that SLK-PE and SLK-NA could promote MIN6 cells proliferation and increasing insulin secretion via PI3K/AKT signaling pathway. Additionally, SLK-PE and SLK-NA have a high level of safety. The findings demonstrate that SLK-PE and SLK-NA could serve as potential functional additives for the prophylaxis and management of diabetes and linked metabolic conditions. • The extracts of small-leaved kudingcha possess significant hypoglycemic activity and higher safety. • The extracts of SLK can improve the insulin secretion of islet β cells. • The extracts of SLK can promote the islet β cell proliferation via PI3K/AKT pathway.