Terrettaz J, Jeanrenaud B
Endocrinology. 1983 Apr;112(4):1346-51. doi: 10.1210/endo-112-4-1346.
The techniques of hyperglycemic and euglycemic clamps previously used in human investigation have been adapted to small rodents to measure in vivo peripheral (muscle, adipose tissues) glucose metabolism and in vivo hepatic glucose production, in lean and genetically obese (fa/fa) rats. The aim of the study was 1) to assess the in vivo relevance of previously described in vitro abnormalities of muscle and adipose tissues producing insulin resistance in genetically obese (fa/fa) rats; 2) to decide whether livers of obese rats were insulin resistant. It was observed that during either hyperglycemic or euglycemic clamps, peripheral glucose metabolism by muscle and adipose tissue of obese rats was similar to that of lean controls but at the cost, for the obese rats, of plasma insulin levels that were 3.5 times higher than control. This indicated that peripheral tissues of obese rats were indeed insulin resistant when tested in vivo. It was also observed that raising plasma insulin levels in lean rats inhibited the in vivo hepatic glucose production. In contrast, in obese rats, hepatic glucose production was high in spite of a marked increase in basal insulinemia. Furthermore, hepatic glucose production of obese rats failed to be inhibited by further increasing their hyperinsulinemia. This is the first demonstration of a hepatic insulin resistance in genetically obese fa/fa rats.
先前用于人体研究的高血糖钳夹技术和正常血糖钳夹技术已被应用于小型啮齿动物，以测量瘦型和遗传性肥胖（fa/fa）大鼠体内外周（肌肉、脂肪组织）葡萄糖代谢及体内肝脏葡萄糖生成情况。本研究的目的是：1）评估先前描述的遗传性肥胖（fa/fa）大鼠肌肉和脂肪组织产生胰岛素抵抗的体外异常情况在体内的相关性；2）确定肥胖大鼠的肝脏是否存在胰岛素抵抗。研究发现，在高血糖钳夹或正常血糖钳夹期间，肥胖大鼠肌肉和脂肪组织的外周葡萄糖代谢与瘦型对照大鼠相似，但肥胖大鼠的血浆胰岛素水平比对照大鼠高3.5倍。这表明肥胖大鼠的外周组织在体内测试时确实存在胰岛素抵抗。研究还发现，提高瘦型大鼠的血浆胰岛素水平可抑制其体内肝脏葡萄糖生成。相反，在肥胖大鼠中，尽管基础胰岛素血症显著增加，但其肝脏葡萄糖生成仍处于高水平。此外，进一步提高肥胖大鼠的高胰岛素血症水平并不能抑制其肝脏葡萄糖生成。这是首次证明遗传性肥胖fa/fa大鼠存在肝脏胰岛素抵抗。
