Fern-9(11)-ene-2α,3β-diol Action on Insulin Secretion under Hyperglycemic Conditions

Abstract

The objective of this study was to investigate the effect and the mechanism of action of fernenediol as an insulin secretagogue. Wistar rats were treated with 0.1, 1, and 10 mg/kg fernenediol before inducing hyperglycemia by oral glucose. The glycaemia, insulin, LDH, calcium, and hepatic glycogen were analyzed. Considering the intestine and pancreas as targets for the triterpene action, the duodenum was used to verify the influence of fernenediol on intestinal glycosidases. Additionally, pancreatic islets were used for studies of C-deoxyglucose uptake and the influx ofCa in hyperglycemic media with/without fernenediol in the presence/absence of an inhibitor/activator of K channels, glibenclamide, diazoxide, nifedipine, calcium chelator (BAPTA-AM), and H-89 and ST, the inhibitors of the PKA and PKC enzymes. Fernenediol significantly reduced glycaemia, potentiated glucose-induced insulin secretion, and stimulated liver glycogen deposition in hyperglycemic rats after an in vivo treatment without changing intestinal disaccharidases activities and showing no influence on intestinal glucose absorption. Also, it stimulated the glucose uptake and calcium influx in pancreatic islets. The involvement of voltage-dependent L-type calcium channels and ATP-dependent potassium channels and the release of calcium from intracellular stores are mandatory for the stimulatory effect of fernenediol on calcium influx. Fernenediol did not change PKA and PKC activities or modify calcium levels. This triterpene is a potent antihyperglycemic agent with a strong insulin secretagogue effect on glycogen accumulation as well. As a whole, this compound presents significant perspectives as a future new drug for the treatment of insulin resistance and/or diabetes.

Uvaol Improves the Functioning of Fibroblasts and Endothelial Cells and Accelerates the Healing of Cutaneous Wounds in Mice

“…Our study demonstrated that the inhibitor PKI-(6-22)-amide prevented the migration of uvaol-provoked fibroblast and endothelial cells; thus, this PKA signaling pathway is likely involved in uvaol-induced migration. These findings support previous studies, which showed that other triterpenoids, such as ursolic acid [39], astragaloside [40], and fernenediol [41], induce the activation of the PKA pathway to generate their pharmacological effects. Of note, the activation of PKA intracellular signaling pathways upregulates ECM production by fibroblasts, contributing to tube formation and the motility of endothelial cells [42,43].…”

Antidiabetic and hypolipidemic potential of Campomanesia xanthocarpa seed extract obtained by supercritical CO2

“…Insulin levels were estimated by means of colorimetric measurements at 450 and 550 nm through interpolation from a standard curve. Samples were analysed in duplicate and results were expressed as ng insulin/ml serum (Castro et al, 2018). The sensitivity of the assay was 5 µUI/mL.…”