Triterpene derivative: A potential signaling pathway for the fern-9(11)-ene-2α,3β-diol on insulin secretion in pancreatic islet

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• 作者：Gabrielle da Luz^a ; Marisa Já ; dna Silva Frederico^a ; Allisson Jhonatan Gomes Castro^a ; Ana Luiza Ludwig Moraes^a ; Francieli Kanumfre de Carvalho^b ; Leandro Espí ; ndola^b ; É ; der Carlos Schmidt^c ; Zenilda Laurita Bouzon^c ; Moacir Geraldo Pizzolatti^b ; Fá ; tima Regina Mena Barreto Silva^a ; ^{mena.barreto@ufsc.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Triterpene ; Glycaemia ; Insulin ; Calcium influx ; Pancreas
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：154
• 期：Complete
• 页码：58-65
• 全文大小：763 K

文摘

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.

Main 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.

Key findings

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.

Significance

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.