Chan T M, Young K M, Hutson N J, Brumley F T, Exton J H
Am J Physiol. 1975 Dec;229(6):1702-12. doi: 10.1152/ajplegacy.1975.229.6.1702.
Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear "forward crossover" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.
对遗传性糖尿病小鼠（db/db）及其正常同窝小鼠的肝脏碳水化合物代谢进行了研究。在db/db小鼠中，身体水分低于正常水平且随年龄下降。在所有研究的年龄段，db/db小鼠的肝脏相对于身体的代谢质量异常大。在db/db小鼠中，肝糖原分解、糖原合成、糖原合成酶和磷酸化酶均显著增加。每100克身体水分中，db/db小鼠灌注肝脏中由丙氨酸或乳酸生成葡萄糖的糖异生作用高于正常水平。db/db小鼠肝脏中果糖-1,6-二磷酸酶、葡萄糖-6-磷酸酶、葡萄糖激酶+己糖激酶和丙酮酸激酶的活性升高。用乳酸灌注的糖尿病小鼠肝脏显示磷酸烯醇丙酮酸浓度显著降低，且果糖-1,6-二磷酸和果糖-6-磷酸之间出现明显的“正向交叉”。用[3-³H]葡萄糖测量的db/db小鼠体内葡萄糖清除率是正常小鼠的170%。所呈现的数据表明，在db/db小鼠的肝脏中：1）在高血糖之前葡萄糖生成增加；2）糖原周转更快；3）糖酵解和糖异生酶异常升高。从病因学角度对这些异常情况进行了讨论。
