title: Borapetoside C from Tinospora crispa improves insulin sensitivity in diabetic mice.
abstract: Diabetes mellitus (DM) often leads to disability from vascular complications and neurological complications. Tinospora crispa has been widely used in Asia and Africa as a remedy for diabetes and other diseases. In this study, we investigated the hypoglycemic actions of borapetoside C isolated from T. crispa, and the mechanisms underlying its actions. Acute treatment with borapetoside C (5mg/kg, i.p.) attenuated the elevated plasma glucose induced by oral glucose in normal and type 2 DM (T2DM) mice. Compared to the effect of injected insulin (0.5 IU/kg), borapetoside C caused a more prominent increase of glycogen content in skeletal muscle of T2DM mice, but a less increase in type 1 DM (T1DM) mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, i.p.) plus insulin enhanced insulin-induced lowering of the plasma glucose level and insulin-induced increase of muscle glycogen content. Continuous treatment with 5mg/kg borapetoside C (twice daily) for 7 days increased phosphorylation of insulin receptor (IR) and protein kinase B (Akt) as well as the expression of glucose transporter-2 (GLUT2) in T1DM mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, twice daily) plus insulin for 7 days enhanced insulin-induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice. This study proved that borapetoside C can increase glucose utilization, delayed the development of insulin resistance and enhanced insulin sensitivity. The activation of IR-Akt-GLUT2 expression and the enhancement of insulin sensitivity may contribute to the hypoglycemic action of borapetoside C in diabetic mice.
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Tun
authors.initials: CT
authors.lastname: Ruan
authors.forename: Sio-Hong
authors.initials: SH
authors.lastname: Lam
authors.forename: Tzong-Cherng
authors.initials: TC
authors.lastname: Chi
authors.forename: Shoei-Sheng
authors.initials: SS
authors.lastname: Lee
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D010946:Plants, Medicinal / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D031610:Tinospora / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D004224:Diterpenes; D051273:Glucose Transporter Type 2; D007004:Hypoglycemic Agents; D007328:Insulin; C495683:Slc2a2 protein, rat; C576563:borapetoside C; D006003:Glycogen; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt