Steviol glucuronide, a metabolite of steviol glycosides, potently stimulates insulin secretion from isolated mouse islets: Studies in vitro

Abstract

Aims Steviol glycosides are the sweet components extracted from medicinal plant Stevia rebaudiana Bertoni, which have antihyperglycaemic effects. Steviol glucuronide (SVG) is the metabolite excreted in human urine after oral administration of steviol glycosides. We aimed to clarify whether SVG exerts direct insulin stimulation from pancreatic islets and to explore its mode of action. Materials and Methods Insulin secretion was measured after 60 minutes static incubation of isolated mouse islets with (a) 10−9‐10−5 mol/L SVG at 16.7 mmol/L glucose and (b) 10−7 mol/L SVG at 3.3‐16.7 mmol/L glucose. Islets were perifused with 3.3 or 16.7 mmol/L glucose in the presence or absence of 10−7 mol/L SVG. Gene transcription was measured after 72 hours incubation in the presence or absence of 10−7 mol/L SVG. Results SVG dose‐dependently increased insulin secretion from mouse islets with 10−7 mol/L exerting the maximum effect in the presence of 16.7 mmol/L glucose (P < .001). The insulinotropic effect of SVG was critically dependent on the prevailing glucose concentration, and SVG (10−7 mol/L) enhanced insulin secretion at or above 11.1 mmol/L glucose (P < .001) and showed no effect at lower glucose concentrations. During perifusion of islets, SVG (10−7 mol/L) had a long‐acting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). Gene‐transcript levels of B2m and Gcgr were markedly altered. Conclusion This is the first report to demonstrate that SVG stimulates insulin secretion in a dose‐ and glucose‐dependent manner from isolated mouse islets of Langerhans. SVG may be the main active metabolite after oral intake of steviol glycosides.

Natural Sweeteners: The Relevance of Food Naturalness for Consumers, Food Security Aspects, Sustainability and Health Impacts

“…Steviol glycosides are hydrolysed to steviol by colonic microbiota. Most steviol is absorbed by the intestine before reaching the liver, where it goes through a process of conjugation with glucuronic acid to produce steviol glucoronides, which are finally excreted mostly in urine [ 102 ]. Consuming steviol glycosides is safe provided it lies within the 4 mg/kg of body weight/day limit [ 103 ].…”

Approaches toward the Separation, Modification, Identification and Scale up Purification of Tetracyclic Diterpene Glycosides from Stevia rebaudiana (Bertoni) Bertoni

“…It has also been described that steviol glycosides stimulates insulin secretion in a dose- and glucose-dependent manner from isolated mouse islets of Langerhans. Steviol glucuronide has been identified in human urine, thus steviol is the main active metabolite after oral intake of steviol glycosides [ 18 , 19 ]. The antihyperglycemic and blood pressure-reducing effects of stevioside in the diabetic Goto-Kakizaki rat and the mechanism of the hypoglycemic effect of stevioside has been described [ 20 , 21 ].…”

Beneficial role of Stevia rebaudiana dry extract on the blood glucose reduction in the chronic diabetes mellitus

“…These results may be mediated through the properties of Stevia rebaudiana as an anti-oxidant and also as an insulin-mimetic agents in the pancreas islets. [6][7][8]12 Not only the stevioside but also the steviol glycoside metabolite gave pivotal role in the reduction of blood glucose concentration.…”

“…7,9,10 It is not only the stevioside that exerts an antidiabetic property but also its metabolite, steviol, that actively increases the uptake of the glucose in the brain and myocardium. 11,12 We have reported that prolonged use of liquid stevia sweetener (equivalent with stevioside 40 mg/kg BW) contributed to the blood glucose reduction in the diabetes mellitus. 13 However, different results were found in the clinical setting.…”