Makino H, Kanatsuka A, Suzuki T, Kuribayashi S, Hashimoto N, Yoshida S, Nishimura M
Diabetes. 1985 Sep;34(9):844-9. doi: 10.2337/diab.34.9.844.
In an attempt to determine the mechanism of insulin resistance in the presence of obesity, we examined effects of insulin on insulin-sensitive phosphodiesterase (PDE) in spontaneously diabetic KK mice. Isolated fat cells prepared from epididymal adipose tissue were incubated, with or without insulin, for 10 min. In the case of subcellular fractionation, only membrane-bound PDE was activated by insulin, as was noted in the case of rat fat cells. The specific activity was decreased in KK mice compared with control C57BL/6 mice. The dose-response curve, expressed as a percent of the maximal insulin effect, shifted to the right and the increase of ED50 indicated a decreased insulin sensitivity in the KK mice. The maximal insulin effect did not change, either when expressed as a percent of the basal enzyme activity or when expressed on a per cell basis. Specific binding of [125I]-insulin in fat cells increased in KK mice and curvilinear Scatchard plots showed an increase of the high-affinity sites. These data indicate that impairment of PDE activation in fat cells of KK mice relates to postreceptor defects and the uncoupling may result in a decreased sensitivity.
为了确定肥胖情况下胰岛素抵抗的机制，我们研究了胰岛素对自发性糖尿病KK小鼠胰岛素敏感磷酸二酯酶（PDE）的影响。从附睾脂肪组织制备的分离脂肪细胞在有或无胰岛素的情况下孵育10分钟。在亚细胞分级分离的情况下，只有膜结合PDE被胰岛素激活，这与大鼠脂肪细胞的情况相同。与对照C57BL/6小鼠相比，KK小鼠的比活性降低。以最大胰岛素效应的百分比表示的剂量反应曲线向右移动，ED50的增加表明KK小鼠的胰岛素敏感性降低。当以基础酶活性的百分比表示或按每个细胞计算时，最大胰岛素效应均未改变。KK小鼠脂肪细胞中[125I]胰岛素的特异性结合增加，曲线型Scatchard图显示高亲和力位点增加。这些数据表明，KK小鼠脂肪细胞中PDE激活受损与受体后缺陷有关，这种解偶联可能导致敏感性降低。
