Inhibition of insulin release by Jatrophone.
In many 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 microM range, probably involving alterations in membrane Ca2+ permeability and/or internal Ca2+ distribution. In collagenase-isolated rat islets and in the absence of glucose, basal insulin secretion measured by radioimmunoassay averaged 122 +/- 13 microU/islet per 90 min (N = 25). At 16.7 mM glucose, the insulin output reached 445 +/- 32 microU/islet per 90 min (N = 27). Jatrophone (1-100 microM/l) caused a dose-related inhibition of glucose-induced insulin release, over basal secretion, with an ID50 close to 8 microM/l. Complete inhibition of insulin release was obtained with 100 microM/l Jatrophone. However, at 100 microM/l (but not at 10 microM/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 +/- 3.63 (N = 42) to 7.48 +/- 1.36 (N = 16) pmol/l per islet. In conclusion, at lower concentrations (10 microM/l) Jatrophone could be a valuable tool for the study of the mechanism of insulin release induced either by glucose or other secretagogues.
Menezes
F V
FV
Departamento de Fisiologia e Biofisica, Universidade Estadual de Campinas, SP, Brasil.
Carneiro
E M
EM
Delattre
E
E
Boschero
A C
AC
D000818:Animals; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004224:Diterpenes; D007328:Insulin; D007329:Insulin Antagonists; C006386:jatrophone