Thorens B, Weir G C, Leahy J L, Lodish H F, Bonner-Weir S
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
Proc Natl Acad Sci U S A. 1990 Sep;87(17):6492-6. doi: 10.1073/pnas.87.17.6492.
Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.
出生2天的大鼠注射单剂量链脲佐菌素后,6周后会发展为非胰岛素依赖型糖尿病。这些糖尿病大鼠的胰腺β胰岛细胞在维持对其他促分泌素(如精氨酸)敏感性的同时,丧失了葡萄糖诱导的胰岛素分泌能力。我们通过胰腺切片免疫荧光染色和胰岛裂解物的蛋白质印迹法,分析了糖尿病胰岛中肝/β细胞葡萄糖转运体异构体的表达水平。糖尿病动物的胰岛中这种β细胞特异性葡萄糖转运体异构体的表达降低,且降低程度与高血糖的严重程度相关。相比之下,糖尿病对肝脏中这种转运体异构体的表达影响极小。因此,β细胞中肝/β细胞葡萄糖转运体异构体表达降低与糖尿病胰岛受损的葡萄糖感应特性相关;我们的数据表明,这种葡萄糖转运体可能是β细胞葡萄糖传感器的一部分。