O'Harte F P, Boyd A C, McKillop A M, Abdel-Wahab Y H, McNulty H, Barnett C R, Conlon J M, Højrup P, Flatt P R
School of Biomedical Sciences, University of Ulster, BT52 1SA, Northern, Coleraine, Ireland.
Peptides. 2000 Oct;21(10):1519-26. doi: 10.1016/s0196-9781(00)00306-5.
Human insulin was glycated under hyperglycemic reducing conditions and a novel diglycated form (M(r) 6135.1 Da) was purified by RP-HPLC. Endoproteinase Glu-C digestion combined with mass spectrometry and automated Edman degradation localized glycation to Gly(1) and Phe(1) of the insulin A- and B-chains, respectively. Intraperitoneal (i.p.) administration of diglycated insulin to mice alone or in combination with glucose (7 nmol/kg) resulted in a 43-61% and 11-34% reduction in glucose lowering activity, respectively, compared with native insulin. Consistent with these findings, diglycated insulin (10(-9) to 10(-7) mol/liter) was 22-38% less effective (P < 0.001) than native insulin in stimulating glucose uptake, glucose oxidation and glycogen production in isolated mouse abdominal muscle.
人胰岛素在高血糖还原条件下发生糖基化，通过反相高效液相色谱法（RP-HPLC）纯化得到一种新型的双糖基化形式（分子量6135.1 Da）。内切蛋白酶Glu-C消化结合质谱分析和自动Edman降解法分别将糖基化定位到胰岛素A链的Gly(1)和B链的Phe(1)上。单独给小鼠腹腔注射（i.p.）双糖基化胰岛素或与葡萄糖（7 nmol/kg）联合注射，与天然胰岛素相比，葡萄糖降低活性分别降低了43%-61%和11%-34%。与这些发现一致，在分离的小鼠腹部肌肉中，双糖基化胰岛素（10^(-9)至10^(-7) mol/升）刺激葡萄糖摄取、葡萄糖氧化和糖原生成的效果比天然胰岛素低22%-38%（P < 0.001）。
