REGULATION OF GLUCOSE-TRANSPORTER AND HEXOKINASE-II EXPRESSION IN TISSUES OF DIABETIC RATS
REGULATION OF GLUCOSE-TRANSPORTER AND HEXOKINASE-II EXPRESSION IN TISSUES OF DIABETIC RATS
复制标题
DOI：
10.1152/ajpendo.1993.265.3.e392
复制
发表时间：
1993-09-01
影响因子：
--
通讯作者：
GIRARD, J
中科院分区：
文献类型：
--
作者：
BURCELIN, R;PRINTZ, RL;GIRARD, J
糖尿病患者肌肉和脂肪组织中葡萄糖转运和磷酸化减少。葡萄糖转运蛋白GLUT-4和己糖激酶II（HK II）是胰岛素敏感组织、脂肪组织、骨骼肌和心脏中参与葡萄糖转运和磷酸化的主要蛋白质亚型。在成年雄性Wistar大鼠给予链脲佐菌素（STZ）后的前3天，研究了葡萄糖转运和磷酸化减少的分子机制。测定GLUT-4 mRNA和蛋白、HK Ⅱ mRNA和酶活性。注射STZ后（30 h），GLUT-4和HK II mRNA分别降低至非糖尿病大鼠的10 +/- 1和20 +/- 3%;它们保持在这些低水平72 h。通过根皮苷输注使血糖水平正常化并没有使GLUT-4和HK II mRNA浓度恢复正常。与此相反，正常化的血糖水平的生理胰岛素输注导致GLUT-4和HK II mRNA浓度的总正常化。当胰岛素治疗停止时，GLUT-4和HK II mRNA和蛋白浓度在6小时内分别下降至对照水平的40%和20%。糖尿病大鼠骨骼肌和心脏中GLUT-4和HK Ⅱ mRNA及HK Ⅱ活性变化最小。我们的结论是GLUT-4和HK II mRNA在白色脂肪组织中协调表达。它们迅速受到血浆胰岛素浓度急性降低的影响，但不受高血糖症的影响。相比之下，骨骼肌和心脏GLUT-4和HK II mRNA受短期糖尿病的影响不大。
Glucose transport and phosphorylation are decreased in muscle and adipose tissue in diabetes mellitus. The glucose transporter GLUT-4 and hexokinase II (HK II) are the main isoforms of proteins involved in glucose transport and phosphorylation in insulin-sensitive tissues, adipose tissue, skeletal muscle, and heart. The molecular mechanisms responsible for the decrease of glucose transport and phosphorylation have been studied during the first 3 days after streptozotocin (STZ) administration in adult male Wistar rats. GLUT-4 mRNA and protein and HK II mRNA and enzyme activity were measured. After the injection of STZ (30 h), GLUT-4 and HK II mRNAs were decreased to 10 +/- 1 and 20 +/- 3% that found in nondiabetic rats, respectively; they remained at these low levels for 72 h. Normalization of the blood glucose level by phlorizin infusion did not restore GLUT-4 and HK II mRNA concentrations to normal. In contrast, normalization of the blood glucose level by physiological infusion of insulin resulted in a total normalization of GLUT-4 and HK II mRNA concentrations. When insulin therapy was stopped, GLUT-4 and HK II mRNA and protein concentrations fell in 6 h to 40 and 20% of control levels, respectively. Minimal changes of GLUT-4 and HK II mRNA, and of HK II activity, were observed in skeletal muscle and heart of diabetic rats. We conclude that GLUT-4 and HK II mRNA are coordinately expressed in white adipose tissue. They are rapidly affected by an acute decrease of the plasma insulin concentrations but are not modified by hyperglycemia. In contrast, skeletal muscle and heart GLUT-4 and HK II mRNA are not greatly affected by short-term diabetes.