Long-term AICAR administration and exercise prevents diabetes in ZDF rats
Long-term AICAR administration and exercise prevents diabetes in ZDF rats
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DOI：
10.2337/diabetes.54.4.928
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发表时间：
2005-04-01
期刊：
影响因子：
7.7
通讯作者：
Lund, S
中科院分区：
文献类型：
--
作者：
Pold, R;Jensen, LS;Lund, S
包括锻炼计划在内的生活方式干预是预防肥胖相关糖尿病的基石。AMP激活的蛋白激酶(AMPK)被认为与运动对糖脂代谢的许多有益影响有关。研究了长期运动训练或5-aminoimidazole-4-carboxamide-1-beta-D-riboruranoside治疗对雄性Zucker糖尿病肥胖大鼠糖尿病发展的影响。5周龄的糖尿病前期ZDF大鼠在8周内每天进行跑步机跑步或AICAR治疗，并与未治疗组进行比较。与未经治疗的大鼠相比，运动和AICAR治疗的大鼠在干预期间都没有出现高血糖。在干预期结束时，通过高胰岛素-正常血糖钳夹来评估全身胰岛素敏感性，运动组和AICAR治疗组的动物与未治疗的ZDF大鼠相比显著增加(P<；0.01)。此外，在运动和AICAR治疗的动物中，胰腺β细胞的形态几乎正常，表明体内慢性激活AMPK可能保留了β细胞的功能。我们的结果表明，AMPK的激活可能代表了一种改善胰岛素作用和防止与2型糖尿病相关的β细胞功能下降的治疗方法。
Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-D-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, prediabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.