インスリン受容体蛋白の減少を示すインスリン受容体異常症の2症例, JRM 1およびJA 3の遺伝子DNAおよびmRNAレベルの異常を検索するため, EB virus-transformed lymphecytesを用いてヒトインスリン受容体cDNAでのSouthern analysisおよびNorthern analysisを行った. Kpn I, Pvu II, Rsa IおよびSac Iにて調べた切断断片にはpolymorphisrnが認められたが, Ban I, Ban II, Bgl II, Hind IIIではみられなかった. しかしいずれの症例も対照にない断片は見いだされず, このpolymorphismが本疾患に特有ではないこと, インスリン受容体遺伝子DNAには大きな欠損や挿入のないことが示唆された. Northern analysisにて検出されたmRNAは対照と同様の分子量およびバンドの強度を示し, 大きな異常のないことが示された. 以上の結果よりこれら2症例のインスリン受容体数の低下の原因は, mRNA転写以後のステップにあることが示唆された.
The insluin-like activity of oxytocin, in stimulating glucose oxidation in several tissues, has been demonstrated recently. This study on the effect of oxytocin on the plasma glucose level was made during induction of labor. Plasma glucose, insulin, glucagon, cortisol and adrenalin levels were measured during oxytocinor prostaglandin F (PGF2α)-induced labor. Oxytocin (8.3 mU/min) or PGF2α (10 g/min) was given to normal pregnant women at term. The plasma oxytocin level was significantly higher in labor induced by oxytocin than in labor induced by PGF2α. The plasma glucose level was decreased by oxytocin, while PGF2α, caused no significant change. Plasma insulin, glucagon, cortisol and adrenalin levels did not change during labor induced by either oxytocin or PGF2α. Further more, at the same duration and interval of uterine contraction, oxytocin decreased the plasma glucose level, while PGF2α had no effect. These findings suggest that the decrease in plasma gluose during oxytocin-induced labor is not due to uterine contraction or insulin secretion, but may be due to an increase in glucose oxidation in the tissues. Oxytocin, in addition to its known physiological roles, may have further metabolic roles and it should be studied for its possible therapeutic use for diabetic patients.
The development of diabetes in NOD mice is a T-cell-dependent autoimmune phenomenon. To clarify which subset of T cells is responsible for the destruction of B cells in islets of NOD mice, we injected precritical NOD mice (12 weeks old) with monoclonal antibodies (anti-L3T4 mAb and anti-Ly-2 mAb), which react with mouse lymphocytes. The administration of anti-L3T4 mAb prevented diabetes in the NOD mice, while anti-Ly-2 mAb failed to do so. Histologically, severe insulitis similar to that in the control mice was observed in both anti-L3T4 mAb-and anti-Ly-2 mAb-trea ted mice. However, the subsets of T cells constructing insulitis were entirely different in the two groups. Ly-2-positive T cells were dominant, while L3T4-positive T cells were absent, in the islets of anti-L3T4 mAb-treated mice. In the anti-Ly-2 mAb-treated group, most of the infiltrated lymphocytes were L3T4-positive T cells, and no Ly-2-positive T cells were observed. These results lead to the conclusion that L3T4-positive T cells may play a major role not only in the development of insulitis but in the destruction of B cells in NOD mice.