Stevioside acts directly on pancreatic β cells to secrete insulin:: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity
Stevioside acts directly on pancreatic β cells to secrete insulin:: Actions independent of cyclic adenosine monophosphate and adenosine triphosphate-sensitive K+-channel activity
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DOI：
10.1016/s0026-0495(00)91325-8
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发表时间：
2000-02-01
影响因子：
9.8
通讯作者：
Hermansen, K
中科院分区：
文献类型：
--
作者：
Jeppesen, PB;Gregersen, S;Hermansen, K
天然甜味剂甜菊苷，这是在植物甜叶菊Bertoni中发现的，多年来一直用于治疗巴拉圭和巴西的印度人的糖尿病。然而，降血糖作用的机制仍不清楚。为了阐明甜菊苷及其配基甜菊醇对来自正常小鼠胰岛和β细胞系INS-1的胰岛素释放的影响。在16.7mmol/L葡萄糖存在下，甜菊苷和甜菊醇（1 nmol/L ~ 1 mmol/L）均剂量依赖性地促进培养的小鼠胰岛分泌胰岛素（P <0.05）。甜菊苷和甜菊醇的促胰岛素分泌作用与葡萄糖浓度密切相关，即甜菊苷（1 mmol/L）和甜菊醇（1 μ mol/L）仅在葡萄糖浓度为8.3 mmol/L或更高时才能促进胰岛素分泌（P <0.05）。有趣的是，甜菊苷和甜菊醇的促胰岛素分泌作用在细胞外Ca ~（2+）缺乏的情况下得以保持。在胰岛灌流过程中，在16.7mmol/L葡萄糖存在下，甜菊苷（1 mmol/L）和甜菊醇（1 μ mol/L）具有持续的、明显可逆的促胰岛素作用（P <0.05）。为了确定甜菊苷和甜菊醇是否直接作用于β细胞，还研究了对INS-1细胞的影响。甜菊苷和甜菊醇均能增强INS-1细胞的胰岛素分泌（P <0.05）。甜菊苷（1 ~ 100 μ mol/L）和甜菊醇（10 nmol/L ~ 10 μ mol/L）均不影响细胞膜K+三磷酸腺苷（K-ATP（+））敏感性通道的活性，也不改变胰岛中环磷酸腺苷（cAMP）水平。总之，甜菊苷和甜菊醇通过直接作用于β细胞刺激胰岛素分泌。结果表明，这些化合物可能具有潜在的作用，作为抗高血糖药物在治疗2型糖尿病。Copyright（C）2000 by W.B.桑德斯公司
The natural sweetener stevioside, which is found in the plant Stevia rebaudiana Bertoni, has been used for many years in the treatment of diabetes among Indians in Paraguay and Brazil. However, the mechanism for the blood glucose-lowering effect remains unknown. To elucidate the impact of stevioside and its aglucon steviol on insulin release from normal mouse islets and the beta-cell line INS-1 were used. Both stevioside and steviol (1 nmol/L to 1 mmol/L) dose-dependently enhanced insulin secretion from incubated mouse islets in the presence of 16.7 mmol/L glucose (P < .05). The insulinotropic effects of stevioside and steviol were critically dependent on the prevailing glucose concentration, ie, stevioside (1 mmol/L) and steviol (1 mu mol/L) only potentiated insulin secretion at or above 8.3 mmol/L glucose (P < .05), Interestingly, the insulinotropic effects of both stevioside and steviol were preserved in the absence of extracellular Ca2+. During perifusion of islets, stevioside (1 mmol/L) and steviol (1 mu mol/L) had a long-lasting and apparently reversible insulinotropic effect in the presence of 16.7 mmol/L glucose (P < .05). To determine if stevioside and steviol act directly on beta cells, the effects on INS-1 cells were also investigated. Stevioside and steviol both potentiated insulin secretion from INS-1 cells (P < .05), Neither stevioside (1 to 100 mu mol/L) nor steviol (10 nmol/L to 10 mu mol/L) influenced the plasma membrane K+ adenosine triphosphate (K-ATP(+))-sensitive channel activity, nor did they alter cyclic adenosine monophosphate (cAMP) levels in islets. In conclusion, stevioside and steviol stimulate insulin secretion via a direct action on beta cells. The results indicate that the compounds may have a potential role as antihyperglycemic agents in the treatment of type 2 diabetes mellitus. Copyright (C) 2000 by W.B. Saunders Company.