EFFECTS OF DIABETES ON MYOCARDIAL GLUCOSE-TRANSPORT SYSTEM IN RATS - IMPLICATIONS FOR DIABETIC CARDIOMYOPATHY

被引:133
作者
GARVEY, WT
HARDIN, D
JUHASZOVA, M
DOMINGUEZ, JH
机构
[1] INDIANA UNIV, SCH MED, DEPT MED, INDIANAPOLIS, IN 46202 USA
[2] INDIANA UNIV, SCH MED, VET ADM MED CTR, NEPHROL SECT, INDIANAPOLIS, IN 46202 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY | 1993年 / 264卷 / 03期
关键词
HEART; MYOCARDIUM; DIABETES-MELLITUS; STREPTOZOTOCIN; GLUT4; GLUCOSE TRANSPORTER PROTEINS; GENE EXPRESSION; INSULIN RESISTANCE;
D O I
10.1152/ajpheart.1993.264.3.H837
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Biochemical mechanisms underlying impaired myocardial glucose utilization in diabetes mellitus have not been elucidated. We studied sarcolemmal vesicles (SL) in control, streptozotocin-induced diabetic (D), and insulin-treated diabetic (Tx) rats and found that 3-O-methylglucose transport rates were decreased 53% in D rats and were normalized by insulin therapy. Immunoblot analyses of SL revealed that GLUT4 glucose transporters were decreased 56% in D and were normal in Tx rats. Thus diminished transport rates could be fully explained by reduced numbers of SL GLUT4 with normal functional activity. To determine whether SL GLUT4 were decreased due to tissue depletion or abnormal subcellular distribution, we measured GLUT4 in total membranes (SL plus intracellular fractions). Total GLUT4 (per mg membrane protein or per DNA) was decreased 45-51% in D [half time = 3.5 days after streptozotocin], and these values were restored to normal in Tx rats. Also, diabetes decreased GLUT4 mRNA levels by 43%, and this effect was reversed by insulin therapy. We conclude that, in diabetes, 1) impaired myocardial glucose utilization is the result of a decrease in glucose transport activity, and 2) transport rates are reduced due to pretranslational suppression of GLUT4 gene expression and can be corrected by insulin therapy. GLUT4 depletion could limit glucose availability under conditions of increased workload and anoxia and could cause myocardial dysfunction.
引用
收藏
页码:H837 / H844
页数:8
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