Triterpene derivative: A potential signaling pathway for the fern-9(11)-ene-2α,3β-diol on insulin secretion in pancreatic islet.
OBJECTIVE
Triterpenes and their derivatives influence on carbohydrate metabolism. In vivo and in vitro treatment investigated the effect of the natural triterpene fern-9(11)-ene-2α,3β-diol (1), isolated from Croton heterodoxus, and a derivative triterpene (2) on glucose homeostasis.


METHODS
The antidiabetic effect of the crude extract from C. heterodoxus leaves, the natural triterpene (1) as well as the derivative triterpene (2) were assayed on glucose tolerance. The effect and the mechanism of action on in vivo treatment with triterpene 2 on glycaemia and insulin secretion were studied. In addition, in vitro studies investigated the mechanism of triterpene 2 on glucose uptake and calcium influx on insulin secretion in pancreatic islets.


RESULTS
The results show the extract slightly reduced the glycaemia when compared with hyperglycemic group. However, the presence of the substituent electron-withdrawing 4-nitrobenzoyl group in the A-ring of triterpene 2 powered the serum glucose lowering compared to triterpene 1. In addition, in vivo treatment with triterpene 2 significantly increased the insulin secretion induced by glucose and stimulated the glucose uptake and calcium influx in pancreatic islet. The effect of triterpene on calcium influx was completely inhibited by diazoxide, nifedipine and stearoylcarnitine treatment.


CONCLUSIONS
The stimulatory effect of triterpene 2 on glucose uptake, calcium influx, regulation of potassium (K(+)-ATP) and calcium (L-VDCCs) channels activity as well as the pathway of PKC highlights the mechanism of action of the compound in pancreatic islets on insulin secretion and glucose homeostasis. In addition, this compound did not induce toxicity in this experimental condition.
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Gabrielle
G
da Luz
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Marisa Jádna Silva
MJ
Frederico
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Allisson Jhonatan Gomes
AJ
Castro
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Ana Luiza Ludwig
AL
Moraes
Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Francieli Kanumfre
FK
de Carvalho
Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Leandro
L
Espíndola
Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Éder Carlos
ÉC
Schmidt
Departamento de Biologia Celular, Embriologia e Genética, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Zenilda Laurita
ZL
Bouzon
Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Moacir Geraldo
MG
Pizzolatti
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: mena.barreto@ufsc.br.
Fátima Regina Mena Barreto
FR
Silva
D000818:Animals; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014315:Triterpenes / Q000494:pharmacology*
D007328:Insulin; D014315:Triterpenes
Calcium influx; Glycaemia; Insulin; Pancreas; Triterpene