AMPK is required for exercise to enhance insulin sensitivity in skeletal muscles

نویسندگان

  • Jørgen Jensen
  • Stephen O'Rahilly
چکیده

The signaling mechanisms by which exercise improves muscle insulin AMPKa is not a sensitive method to judge AMPK activation. So, 172 sensitivity seem even harder to solve than to get people to exercise. Exercise (muscle contraction) has two diverse effects on muscle glucose metabolism. Firstly, acute exercise stimulates glucose uptake in skeletal muscles via translocation of GLUT4 translocation. This effect is insulin independent, and glucose uptake remains elevated a couple of hours after termination of exercise. Secondly, exercise increases insulin sensitivity in skeletal muscles. This latter effect remains for many hours after cessation of exercise, and is obviously insulin dependent. Indeed, candidates have been abundant for both effects of exercise, but convincing signalling mechanisms have not emerged [1]. From a health perspective, the improved muscle insulin sensitivity in the period after exercise improves metabolic regulation. The observation that muscle contraction increases insulin action in prior active muscle was reported in 1982 by Richter et al. [2]. Until now, the most important finding on the mechanisms governing insulin action after exercise is the reports from Holloszy’s laboratory in the 1980s describing that the glycogen content in muscles determines insulin sensitivity after exercise. These studies showed that carbohydrate feeding reduced insulin sensitivity in muscles, whereas insulin sensitivity remained elevated when muscle glycogen content was kept low [3,4]. Indeed, glycogen has kept its central position in regulation of insulin action and capacity to store glucose in muscles [5,6], but little progress has occurred on the mechanisms for elevated muscle insulin sensitivity after exercise. It was obvious to look for enhanced activation of the insulin signaling pathway, but this research has been discouraging. In fact, we found that exercise reduced insulin-stimulated IRS-1 associated PI-3 kinase activity [7]. Other studies, including studies of man, have also found that increased insulin-stimulated glucose uptake following exercise is not associated with enhanced activation of the proximal insulin signalling pathway [8]. The limited progress in our understanding of the mechanisms regulating insulin sensitivity may result from most researchers’ focus on enhanced activation of insulin signaling rather than other signaling mechanisms. In a ground-breaking paper published in Diabetes, Kjøbsted et al. link AMPK to improved insulin sensitivity after exercise [9]. Professor Jørgen Wojtaszewski’s group shows that AMPK activity is required for muscle contraction to increase insulin sensitivity as deletion of the two catalytic subunits (a1 and a2) prevented the ability of exercise to increase insulin sensitivity. Kjøbsted et al. also highlight another wellknown problem in the AMPK field; the Thr phosphorylation of

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2017