Abstract
Stevia rebaudiana (Bert.) Bertoni besides being a source of noncaloric sweeteners is also an important source of bioactive molecules. Many plant extracts, mostly obtained with ethyl acetate solvent, are rich in polyphenol compounds that present insulinotropic effects. To investigate whether the nonsweetener fraction, which is rich in phenolic compounds isolated from Stevia rebaudiana with the solvent ethyl acetate (EAF), has an insulinotropic effect, including interference at the terminals of the autonomic nervous system of the pancreatic islets of rats. Pancreatic islets were isolated from Wistar rats and incubated with EAF and inhibitory or stimulatory substances of insulin secretion, including cholinergic and adrenergic agonists and antagonists. EAF potentiates glucose-stimulated insulin secretion (GSIS) only in the presence of high glucose and calcium-dependent concentrations. EAF increased muscarinic insulinotropic effects in pancreatic islets, interfering with the muscarinic receptor subfamily M3. Adrenergic inhibitory effects on GSIS were attenuated in the presence of EAF, which interfered with the adrenergic α 2 receptor. Results suggest that EAF isolated from stevia leaves is a potential therapy for treating type 2 diabetes mellitus by stimulating insulin secretion only in high glucose concentrations, enhancing parasympathetic signal transduction and inhibiting sympathetic signal transduction in beta cells.
Highlights
Stevia rebaudiana (Bert.) Bertoni is exploited worldwide for its leaves, which contain in diterpene glycosides with high sweetening power [1, 2] that is up to 300 times greater than that of sucrose [3]
In view of the complexity of the process of modulating insulin secretion and the lack of studies showing the mechanisms by which the substances produced by stevia act on glycemic homeostasis, the objective of the present study was to test whether the fraction of stevia isolated with the solvent ethyl acetate (EAF), rich in phenolic compounds and low contamination of glycosides, interferes with insulin secretion stimulated by glucose in the presence or absence of autonomic nervous system (ANS) neurotransmitters
An antagonist of the α2 receptor, increased glucose-stimulated insulin secretion (GSIS) by 42%, and in the presence of ethyl acetate fraction (EAF), this increase was approximately 3 times greater (p < 0 001). Both in the presence and absence of EAF, the reduction of GSIS caused by propranolol, an antagonist of β1 and β2 receptors, was approximately 70%. This is the first work that evaluates the effects on insulin secretion by a fraction of extracts of Stevia rebaudiana that is rich in phenolic compounds and nonsweetener
Summary
Stevia rebaudiana (Bert.) Bertoni is exploited worldwide for its leaves, which contain in diterpene glycosides with high sweetening power [1, 2] that is up to 300 times greater than that of sucrose [3]. Stevia sweeteners, which are nontoxic and nonmutagenic compounds [4], are an alternative to artificial sweeteners that, despite widespread use, are still of concern. Animal studies indicate that artificial sweeteners promote food intake and body weight gain and induce metabolic changes that increase the risks of obesity, type 2 diabetes mellitus (DM2), and cardiovascular disease [5]. Does not cause cardiometabolic dysfunctions [6]. The results reported in the literature, in different experimental animal models as well as in humans, indicated that stevia has hypoglycemic properties [7,8,9], stimulating insulin secretion in vitro [10,11,12] and presenting antihyperglycemic, insulinotropic, and glucostatic effects [13, 14]
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