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

Luz, Gabrielle da; Frederico, Marisa Jádna Silva; Castro, Allisson Jhonatan Gomes; Moraes, Ana Luiza Ludwig; Carvalho, Francieli Kanumfre de; Espíndola, Leandro; Schmidt, Éder C.; Bouzon, Zenilda L.; Pizzolatti, Moacir Geraldo; Silva, Fátima Regina Mena Barreto

doi:10.1016/j.lfs.2016.04.027

Cited by 13 publications

(7 citation statements)

References 45 publications

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“…This may be attributed to the previously reported anti-hyperglycaemic properties of triterpenes which includes myocytes and adipocytes glucose uptake through promoting glucose transpoter-4(GLUT-4) translocation to the cellular membrane [30]. Moreover, triterpenes are also known to inhibit the protein tyrosine phosphatase enzymes [31]. These enzymes are involved in the dephosphorylation of the beta-subunit of the insulin receptor and subsequently result in the impairment of the insulin dependent glucose uptake [32].…”

Section: Discussionmentioning

confidence: 99%

Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors

et al. 2019

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The pathogenesis of prediabetes is associated with risk factors such as chronic consumption of an unhealthy diet. Recent studies have reported that diet-induced pre-diabetes is also associated with risk factors of cardiovascular complications, hence this study was aimed at evaluating the effects of oleanolic acid (OA) on pre-diabetes rats. Pre-diabetes was induced by chronic exposure of Sprague Dawley rats (SD) to high-fat high-carbohydrate diet (20 weeks), whereas the non-pre-diabetes control (NC) was given standard rat chow. Pre-diabetes animals were grouped into five groups namely prediabetes control (PC), metformin treated (Met), metformin with diet intervention (Met + DI), oleanolic acid treated (OA), and oleanolic acid with diet intervention (OA + DI) then treated for 12 weeks. At the end of treatment, all animals were sacrificed where organs and tissues were harvested for biochemical analysis and histological studies. The results showed that PC had a significantly higher triglycerides (TGs), low density lipoprotein cholesterol (LDL-C, interleukin-6(IL-6), tumor necrosis factor alpha (TNFα), C-reactive protein (CRP), mean arterial pressure (MAP) and hearts weights in comparison to NC (p < 0.05). However, the administration of OA, in both the presence and absence of dietary intervention showed a significant decrease in TGs, LDL-C, IL-6, TNFα, CRP, MAP, hearts weights (p < 0.05). In conclusion, the administration of OA was able to lower the risks of developing CVDs in pre-diabetes rat model through ameliorating dyslipidaemia, oxidative stress, hypertension, and low-grade inflammation. Therefore OA has the potential to be used as an alternative treatment to prevent the onset of CVDs during pre-diabetes stage even in the absence of dietary and lifestyle intervention.

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Section: Discussionmentioning

confidence: 99%

Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors

et al. 2019

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“…This effect on serum glucose lowering may be mediated by a combination of different mechanisms such as an increase in insulin secretion and/or the stimulation of glucose uptake and utilization in peripheral tissues . Fernenediol has already been described as a potential antihyperglycemic agent by Da Luz et al Additionally, the effects on glucose metabolism and the maintenance of glucose homeostasis have already been described for triterpenes from different classes. − , In terms of whole-body glucose homeostasis, the liver is responsible for removing part of the ingested glucose from the circulation and stores it in the form of glycogen or metabolizes it through glycolysis to minimize the fluctuation of glycaemia . In terms of glycogen metabolism, fernenediol significantly increased the liver glycogen content after the oral treatment in hyperglycemic rats.…”

Section: Discussionmentioning

confidence: 99%

“…EZRMI-13K) was obtained from Millipore (Sts Charles, MO, USA). [U- 11)-ene-2α,3β-diol) was isolated from the hexane fraction of the crude hydroalcoholic extract obtained of the C. heterodoxus (aerial parts) as described by Carvalho 19 and Da Luz et al 20 2.3. Animals.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2018

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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.

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“…Scheen reported that new insulin secretagogues should offer advantages over sulfonylureas in the near feature. [ 14 ] Most of the plants contain substances that have antidiabetic effect and insulin secretagogue as plant extracts, functional foods,[ 15 16 17 18 ] and some isolated as triterpenes and derivatives,[ 19 20 ] phytosterols,[ 21 22 ] stilbene,[ 23 ] and iridoid glycoside[ 24 ] have shown activity which stimulates or potentiates insulin secretion in pancreatic islets.…”

Section: Introductionmentioning

confidence: 99%

Influence of flavonoids on mechanism of modulation of insulin secretion

Soares¹,

Leal²,

Silva³

et al. 2017

Phcog Mag

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Background:The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue.Objective:To study the influence of flavonoid on overall modulation mechanisms of insulin secretion.Methods:The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells.Results:Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases.Conclusion:According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes.SUMMARY The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: KATP channels: ATP-sensitive K+ channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca+2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca2+/calmodulin-dependent protein kinase II, GSIS: Glucose-stimulated insulin secretion, Insig-1: Insulin-induced gene 1, IRS-2: Insulin receptor substrate 2, PDX-1: Pancreatic and duodenal homeobox 1, SREBP-1c: Sterol regulatory element binding protein-1c, DMC: Dihydroxy-6’-methoxy-3’,5’-dimethylchalcone, GLP-1: Glucagon-like peptide-1, GLP-1R: Glucagon-like peptide 1 receptor.

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

Cited by 13 publications

References 45 publications

Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors

Plant-Derived Oleanolic Acid (OA) Ameliorates Risk Factors of Cardiovascular Diseases in a Diet-Induced Pre-Diabetic Rat Model: Effects on Selected Cardiovascular Risk Factors

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

Influence of flavonoids on mechanism of modulation of insulin secretion

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