Smellie W S, O'Donnell J, Davidson H, Couper J, Logue F C
Institute of Biochemistry, Glasgow Royal Infirmary.
J Clin Pathol. 1994 Nov;47(11):982-5. doi: 10.1136/jcp.47.11.982.
To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism.
Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism.
Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05).
The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.
检验酸碱或钙浓度的改变可能影响胰岛素原加工或胰岛素分泌机制这一假说。
通过在三种酸碱和钙紊乱模型中测量血清完整胰岛素原和免疫反应性胰岛素浓度，评估胰岛素原分泌或裂解的变化：（1）六名志愿者在三个为期五天的时间段内分别口服安慰剂、氯化铵或碳酸氢钠，观察酸碱状态的亚急性变化；（2）八名受试者口服25 mmol钙后，观察钙浓度的急性变化；（3）七名原发性甲状旁腺功能亢进患者和五名假性甲状旁腺功能减退患者，观察钙浓度的慢性变化。
血清碳酸氢盐浓度升高证实了酸碱变化（p<0.01）。未发现血清胰岛素、完整胰岛素原或胰岛素原：胰岛素摩尔比有变化。急性钙负荷后两小时，血清钙浓度升高（2.49对2.38 mmol/L；p<0.05），甲状旁腺激素浓度降低（1.1对1.9 pmol/L；p<0.01）。血清葡萄糖、胰岛素或完整胰岛素原浓度无显著差异。甲状旁腺功能亢进组空腹胰岛素原浓度显著较低（1.1对2.1 pmol/L；p<0.05），甲状旁腺切除术后显著升高（2.1对1.1 pmol/L；p<0.05）。
结果表明亚急性酸碱变化不影响胰岛素原裂解。虽然急性钙负荷无明显作用，但慢性高钙血症可能影响胰岛素分泌机制。
