Inhibition of insulin release by jatrophone

ABSTRACT

In may countries, including Brazil, extracts of Jatrophona elliptica species are currently used for the treatment of several diseases. Recently it was shown that a purified compound from these plants inhibits contraction of smooth and cardiac muscle in the uM range, probably involving alterations membrane Ca2+ permeability and/or internal Ca2+ distribution. In the collagenase-isolated rat islets and in the absence of glucose, basal insulin secretion measured by radioimmunoassay averaged 122 ñ 13 uU/islet per 90 min (N=27). Jatrophone (1-100 uM/l) caused a dose-related inhibition of glucose-induced insulin release, over basal secretion, with an ID50 close to 8 uM/l. Complete inhibition of insulin release was obtained with 100 uM/l Jatrophone. However, at 100 uM/l (but not at 10 uM/l) concentration, Jatrophone also provoked a reduction in glucose metabolism by the islets which could explain, at least in part, the reduction in insulin secretion. After 120-min incubation,. the glucose metabolism, measured by the 14CO2 production, was reduced from 26.58 ñ 3.63 (N=42) to 7.48 ñ 1.36 (N=16) pmol/l per islet. In conclusion at lower concentrations (10 uM/l) Jatrophone could be a valuable tool for the study of the mechanism of insulin release induced either by glucose or other secretagogues