Amherdt M, Harris V, Renold A E, Orci L, Unger R H
J Clin Invest. 1974 Jul;54(1):188-93. doi: 10.1172/JCI107742.
Exogenous glucagon is known to increase hepatic lysosomes, but the relationships between endogenous glucagon and insulin levels and hepatic lysosomes have not been examined. To determine if the hormones of the pancreatic islets influence the development of these organelles glycogenosomes, dense bodies, and autophagosomes were morphometrically quantitated in normal rats, in rats with mild streptozotocin diabetes with normal hormone levels, and in rats with severe streptozotocin diabetes with hyperglucagonemia, hypo-insulinemia, and clinical evidence of uncontrolled diabetes and ketoacidosis. In the latter volume density of lysosomes averaged 222.8x10(-4) (SEM +/-19.8x10(-4)), significantly above the control value of 75x10(-4) (SEM +/-7.0x10(-4)) (P<0.0005); glycogenosomes were absent in the diabetics, the increase being largely the result of increased autophagosomes. Insulin treatment corrected the hyperglucagonemia, hypoinsulinemia, and other manifestations of uncontrolled diabetes and reduced the volume density of lysosomes to 37.4x10(-4) (SEM +/-2.0x10(-4)), significantly below both the untreated diabetic rats and the nondiabetic controls (P<0.0025). In mild streptozotocin diabetes, in which hyperglucagonemia, hypoinsulinemia, and other evidence of uncontrolled diabetes were absent, lysosomes averaged 77.6x10(-4) (SEM +/-5.5x10(-4)), not different from the controls. A statistically significant correlation between all measurements of lysosomal volume density and plasma glucagon was observed (r=0.79; P<0.001). It is concluded that uncontrolled streptozotocin diabetes in rats is accompanied by hepatic autophagy which may be related to the increased plasma glucagon level and/or the decreased insulin and which is corrected by insulin therapy.
已知外源性胰高血糖素可增加肝脏溶酶体，但内源性胰高血糖素和胰岛素水平与肝脏溶酶体之间的关系尚未得到研究。为了确定胰岛激素是否会影响这些细胞器（糖原小体、致密体和自噬体）的发育，对正常大鼠、激素水平正常的轻度链脲佐菌素糖尿病大鼠以及患有高胰高血糖素血症、低胰岛素血症且有未控制糖尿病和酮症酸中毒临床证据的重度链脲佐菌素糖尿病大鼠的这些细胞器进行了形态计量学定量分析。在后者中，溶酶体的体积密度平均为222.8×10⁻⁴（标准误±19.8×10⁻⁴），显著高于对照组值75×10⁻⁴（标准误±7.0×10⁻⁴）（P<0.0005）；糖尿病大鼠中不存在糖原小体，增加主要是自噬体增加的结果。胰岛素治疗纠正了高胰高血糖素血症、低胰岛素血症以及未控制糖尿病的其他表现，并将溶酶体的体积密度降低至37.4×¹⁰⁻⁴（标准误±2.0×10⁻⁴），显著低于未治疗的糖尿病大鼠和非糖尿病对照组（P<0.0025）。在轻度链脲佐菌素糖尿病中，不存在高胰高血糖素血症、低胰岛素血症和未控制糖尿病的其他证据，溶酶体平均为77.6×10⁻⁴（标准误±5.5×10⁻⁴），与对照组无差异。观察到溶酶体体积密度的所有测量值与血浆胰高血糖素之间存在统计学显著相关性（r=0.79；P<0.001）。得出的结论是，大鼠未控制的链脲佐菌素糖尿病伴有肝脏自噬，这可能与血浆胰高血糖素水平升高和/或胰岛素降低有关，并且可通过胰岛素治疗得到纠正。
