IMPAIRMENT OF INSULIN ACTION ON PERIPHERAL GLUCOSE-UPTAKE AND HEPATIC GLUCOSE-PRODUCTION IN TUMOR-BEARING RATS

被引:5
作者
LANG, CH [1 ]
SKREPNIK, N [1 ]
DOBRESCU, C [1 ]
BURNS, AH [1 ]
机构
[1] LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,NEW ORLEANS,LA 70112
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 265卷 / 02期
关键词
CANCER; LEUKOCYTOSIS; GLUCOSE UTILIZATION; INSULIN-MEDIATED GLUCOSE UPTAKE; GLUCOSE UPTAKE; NON-INSULIN-MEDIATED GLUCOSE UPTAKE; INSULIN RESISTANCE; CACHEXIA; FASTING;
D O I
10.1152/ajpregu.1993.265.2.R356
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The present study was performed to determine the time-course for the development of peripheral and hepatic insulin resistance in rats as a result of an increasing tumor burden. Animals were inoculated with Yoshida ascites hepatoma, and studies were conducted during the early phase of tumor growth (day 4) at which time there was no change in food intake and at a later time point (day 8) when the tumor burden was increased and rats demonstrated anorexia. In vivo insulin action was accessed under euglycemic hyperinsulinemic conditions, in which insulin was infused at rates sufficient to produce arterial insulin levels that represent high physiological (3.5 ng/ml) or maximally stimulating values (180 ng/ml). On day 4, tumor-bearing (TB) rats were euglycemic, and whole body glucose turnover was elevated 32%. Insulin-mediated glucose uptake (IMGU) in TB rats was similar to control values at the low insulin infusion rate but reduced by 53% under maximally stimulating conditions. The insulin-induced suppression of glucose production was similar in TB and control animals at this time point. In contrast, on day 8, TB rats were hypoglycemic and glucose turnover was reduced 35%. The impairment in IMGU was more severe than seen earlier, with glucose uptake being reduced 39 and 61% at both levels of hyperinsulinemia. At this time point, the ability of insulin to inhibit glucose production was also impaired. These results indicate that the insulin resistance induced by the Yoshida hepatoma was manifested initially by a reduction in IMGU by peripheral tissues. As the tumor burden increased peripheral insulin resistance became more severe and an impairment in hepatic insulin action was observed.
引用
收藏
页码:R356 / R364
页数:9
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