Krook A, Roth R A, Jiang X J, Zierath J R, Wallberg-Henriksson H
Department of Clinical Physiology, Karolinska Hospital, Stockholm, Sweden.
Diabetes. 1998 Aug;47(8):1281-6. doi: 10.2337/diab.47.8.1281.
The serine/threonine kinase Akt (PKB/Rac) has been implicated as playing a role in the insulin-signaling pathway to glucose transport. Little is known regarding the regulation of Akt kinase activity in insulin-sensitive tissues, such as skeletal muscle, or whether this regulation is altered in insulin-resistant states such as NIDDM. We examined the effect of insulin on Akt kinase activity in skeletal muscle from six NIDDM patients and six healthy subjects. Whole-body insulin sensitivity, assessed by the euglycemic-hyperinsulinemic clamp, was significantly lower in NIDDM subjects (P < 0.001), and this was accompanied by impaired in vitro insulin-stimulated glucose transport in skeletal muscle. In both groups, insulin induced a significant increase in Akt kinase activity, but the response to maximal insulin (60 nmol/l) was markedly reduced in skeletal muscle from NIDDM subjects (66% of control levels, P < 0.01). Impaired Akt kinase activity was not accompanied by decreased protein expression of Akt. Instead, a trend toward increased Akt expression was noted in skeletal muscle from NIDDM subjects (P < 0.1). These parallel defects in insulin-stimulated Akt kinase activity and glucose transport in diabetic skeletal muscle suggest that reduced Akt kinase activity may play a role in the development of insulin resistance in NIDDM.
丝氨酸/苏氨酸激酶Akt（PKB/Rac）被认为在胰岛素信号传导至葡萄糖转运的途径中发挥作用。关于胰岛素敏感组织（如骨骼肌）中Akt激酶活性的调节，以及在诸如非胰岛素依赖型糖尿病（NIDDM）等胰岛素抵抗状态下这种调节是否改变，目前所知甚少。我们研究了胰岛素对6名NIDDM患者和6名健康受试者骨骼肌中Akt激酶活性的影响。通过正常血糖-高胰岛素钳夹技术评估的全身胰岛素敏感性，在NIDDM受试者中显著降低（P<0.001），并且这伴随着骨骼肌中体外胰岛素刺激的葡萄糖转运受损。在两组中，胰岛素均诱导Akt激酶活性显著增加，但NIDDM受试者骨骼肌对最大胰岛素浓度（60 nmol/l）的反应明显降低（为对照水平的66%，P<0.01）。Akt激酶活性受损并未伴随Akt蛋白表达降低。相反，在NIDDM受试者的骨骼肌中观察到Akt表达有增加的趋势（P<0.1）。糖尿病骨骼肌中胰岛素刺激的Akt激酶活性和葡萄糖转运的这些平行缺陷表明，降低的Akt激酶活性可能在NIDDM胰岛素抵抗的发生中起作用。
