Collison M, James D J, Graham D, Holman G D, Connell J M C, Dominiczak A F, Gould G W, Salt I P
The Henry Wellcome Laboratory of Cell Biology, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK.
Diabetologia. 2005 Mar;48(3):539-46. doi: 10.1007/s00125-005-1674-x. Epub 2005 Feb 24.
AIMS/HYPOTHESIS: Insulin-stimulated glucose transport is impaired in a genetic model of hypertension, the stroke-prone spontaneously hypertensive rat (SHRSP), yet the molecular mechanisms that underlie this defect in the animals remain unclear.
We examined the effects of insulin on the trafficking of the insulin-responsive glucose transporter GLUT4 to the plasma membrane in isolated adipocytes from SHRSP and normotensive control Wistar-Kyoto (WKY) rats.
Treatment of isolated adipocytes with insulin resulted in trafficking of GLUT4 to the plasma membrane. There was no significant difference in the magnitude of insulin-stimulated GLUT4 trafficking from intracellular membranes to the plasma membrane between strains. In contrast, we demonstrated that there is a significant reduction in GLUT4 accessible to the glucose photolabel Bio-LC-ATB-BGPA at the plasma membrane of SHRSP adipocytes compared with control rats.
CONCLUSIONS/INTERPRETATION: We propose that a large proportion of GLUT4 translocated to the plasma membrane in response to insulin is not able to bind substrate and catalyse transport in the SHRSP. Therefore, there is a reduction in bioavailable GLUT4 in SHRSP animals that is likely to account, at least in part, for the reduced insulin-stimulated glucose uptake.
目的/假设：在高血压的遗传模型——易卒中型自发性高血压大鼠（SHRSP）中，胰岛素刺激的葡萄糖转运受损，但该动物模型中此缺陷的分子机制仍不清楚。
我们研究了胰岛素对从SHRSP和血压正常的对照Wistar-Kyoto（WKY）大鼠分离的脂肪细胞中胰岛素反应性葡萄糖转运体GLUT4转运至质膜的影响。
用胰岛素处理分离的脂肪细胞导致GLUT4转运至质膜。不同品系间胰岛素刺激的GLUT4从细胞内膜转运至质膜的幅度无显著差异。相比之下，我们证明，与对照大鼠相比，SHRSP脂肪细胞质膜上可被葡萄糖光标记物Bio-LC-ATB-BGPA作用的GLUT4显著减少。
结论/解读：我们提出，在SHRSP中，很大一部分响应胰岛素转运至质膜的GLUT4无法结合底物并催化转运。因此，SHRSP动物中生物可利用的GLUT4减少，这可能至少部分解释了胰岛素刺激的葡萄糖摄取减少的原因。
