Laboratory of Ion Channel Research, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
TRP Research Platform Leuven (TRPLe), KU Leuven, Herestraat 49/802, 3000 Leuven, Belgium.
Nat Commun. 2017 Mar 31;8:14733. doi: 10.1038/ncomms14733.
Steviol glycosides (SGs), such as stevioside and rebaudioside A, are natural, non-caloric sweet-tasting organic molecules, present in extracts of the scrub plant Stevia rebaudiana, which are widely used as sweeteners in consumer foods and beverages. TRPM5 is a Ca-activated cation channel expressed in type II taste receptor cells and pancreatic β-cells. Here we show that stevioside, rebaudioside A and their aglycon steviol potentiate the activity of TRPM5. We find that SGs potentiate perception of bitter, sweet and umami taste, and enhance glucose-induced insulin secretion in a Trpm5-dependent manner. Daily consumption of stevioside prevents development of high-fat-diet-induced diabetic hyperglycaemia in wild-type mice, but not in Trpm5 mice. These results elucidate a molecular mechanism of action of SGs and identify TRPM5 as a potential target to prevent and treat type 2 diabetes.
甜菊糖苷(SGs),如甜菊苷和莱鲍迪苷 A,是天然的、无热量的、有甜味的有机分子,存在于甜叶菊 Stevia rebaudiana 的提取物中,被广泛用作消费者食品和饮料中的甜味剂。TRPM5 是一种在 II 型味觉受体细胞和胰腺β细胞中表达的 Ca2+激活阳离子通道。在这里,我们表明甜菊苷、莱鲍迪苷 A 及其苷元甜菊醇可增强 TRPM5 的活性。我们发现 SGs 可增强苦味、甜味和鲜味的感知,并以 Trpm5 依赖的方式增强葡萄糖诱导的胰岛素分泌。在野生型小鼠中,每天食用甜菊苷可预防高脂肪饮食引起的糖尿病高血糖的发展,但在 Trpm5 小鼠中则不行。这些结果阐明了 SGs 的作用机制,并确定 TRPM5 是预防和治疗 2 型糖尿病的潜在靶点。