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松醇的胰岛素样作用。

Insulin-like effect of pinitol.

作者信息

Bates S H, Jones R B, Bailey C J

机构信息

School of Life and Health Sciences, Aston University, Birmingham, USA.

出版信息

Br J Pharmacol. 2000 Aug;130(8):1944-8. doi: 10.1038/sj.bjp.0703523.

Abstract

D-pinitol (3-O-methyl-chiroinositol), an active principle of the traditional antidiabetic plant Bougainvillea spectabilis, is claimed to exert insulin-like effects. This study investigates the effect of D-pinitol on glucose homeostasis in animal models of diabetes, and on glucose transport by cultured muscle cells. Plasma glucose concentrations were measured in normal, obese-diabetic (ob/ob) and streptozotocin (STZ)-diabetic mice after oral (p.o.) and intraperitoneal (i.p.) administration of D-pinitol. Glucose transport was measured in L6 rat muscle cells by 2-deoxyglucose (2DG) uptake. In STZ-diabetic mice, 100 mg kg(-1) p.o. D-pinitol acutely decreased the hyperglycaemia (by 22% at 6 h). A similar decrease in plasma glucose (by 21%) was observed after 100 mg kg(-1) i.p. D-pinitol. Insulin concentrations and the rate of insulin-induced (1 unit kg(-1) actrapid i.p.) glucose disappearance were not altered by 100 mg kg(-1) p.o. D-pinitol. Chronic administration of D-pinitol (100 mg kg(-1) i.p. twice daily for 11 days) to STZ-diabetic mice maintained a reduction in plasma glucose concentrations from about 14 to 10 mmol l(-1). In normal non-diabetic and severely insulin resistant ob/ob mice, 100 mg kg(-1) p.o. D-pinitol did not significantly affect plasma glucose or insulin during acute studies. Incubation of L6 muscle cells with D-pinitol (10(-3) M) increased basal 2DG uptake by 41% after 10 min and by 34% after 4 h. The effect of D-pinitol was inhibited by the phosphatidylinositol 3-kinase inhibitor LY294002. D-pinitol did not increase insulin-stimulated 2DG uptake by L6 cells. The data support the view that D-pinitol can exert an insulin-like effect to improve glycaemic control in hypoinsulinaemic STZ-diabetic mice. D-pinitol may act via a post-receptor pathway of insulin action affecting glucose uptake.

摘要

D-松醇(3-O-甲基-手性肌醇)是传统抗糖尿病植物叶子花属植物的一种活性成分,据称具有胰岛素样作用。本研究调查了D-松醇对糖尿病动物模型中葡萄糖稳态以及对培养的肌肉细胞葡萄糖转运的影响。在正常、肥胖糖尿病(ob/ob)和链脲佐菌素(STZ)诱导的糖尿病小鼠口服(p.o.)和腹腔注射(i.p.)D-松醇后,测量血浆葡萄糖浓度。通过2-脱氧葡萄糖(2DG)摄取来测量L6大鼠肌肉细胞中的葡萄糖转运。在STZ诱导的糖尿病小鼠中,口服100 mg kg⁻¹ D-松醇可使高血糖急性降低(6小时时降低22%)。腹腔注射100 mg kg⁻¹ D-松醇后,观察到血浆葡萄糖有类似程度的降低(降低21%)。口服100 mg kg⁻¹ D-松醇不会改变胰岛素浓度以及胰岛素诱导的(腹腔注射1单位kg⁻¹ Actrapid)葡萄糖消失率。对STZ诱导的糖尿病小鼠长期给予D-松醇(腹腔注射100 mg kg⁻¹,每日两次,共11天)可使血浆葡萄糖浓度从约14 mmol l⁻¹降至10 mmol l⁻¹。在正常非糖尿病和严重胰岛素抵抗的ob/ob小鼠中,急性研究期间口服100 mg kg⁻¹ D-松醇对血浆葡萄糖或胰岛素没有显著影响。用D-松醇(10⁻³ M)孵育L6肌肉细胞10分钟后,基础2DG摄取增加41%,4小时后增加34%。D-松醇的作用被磷脂酰肌醇3-激酶抑制剂LY294002抑制。D-松醇不会增加L6细胞对胰岛素刺激的2DG摄取。这些数据支持这样一种观点,即D-松醇可以发挥胰岛素样作用,改善低胰岛素血症的STZ诱导的糖尿病小鼠中的血糖控制。D-松醇可能通过胰岛素作用的受体后途径发挥作用,影响葡萄糖摄取。

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