Wang M W, Carlo P, Fineman M, Rink T J, Young A A
Department of Physiology, Amylin Pharmaceuticals, Inc., San Diego, California 92121.
Endocr Res. 1992;18(4):321-32. doi: 10.3109/07435809209111040.
Amylin has been reported to influence carbohydrate metabolism in rats, dogs and cats. We report here that intravenous injection of 50 micrograms amylin (640 nmol/kg) induced hyperglycemia, hyperlactemia, and hypocalcemia in both fed and 5-hour fasted mice. Peak glucose and lactate increments occurred within 15 minutes of treatment, followed by a slower decline of plasma calcium levels. To determine dose-response characteristics of these effects, fasted animals were given amylin doses ranging from 0.005 micrograms to 500 micrograms (64 pmol/kg to 6.4 mumol/kg). Median effective doses (ED50) for the hyperglycemic, hyperlactemic, and hypocalcemic effects were 155, 16.9 and 190 nmol/kg, respectively, with maximum increases of 6.27 mM for glucose, 1.85 mM for lactate and maximum decrease of 0.37 mM for calcium. The estimated half-life (t1/2) of exogenous amylin in the circulation was 5.0 minutes in fasted mice. These results indicate that amylin is bioactive in mice. The kinetic data predict that biologically effective doses of exogenous amylin result in plasma concentrations comparable to pathophysiological concentrations of endogenous hormone previously reported.
据报道，胰岛淀粉样多肽对大鼠、狗和猫的碳水化合物代谢有影响。我们在此报告，静脉注射50微克胰岛淀粉样多肽（640纳摩尔/千克）可使喂食和禁食5小时的小鼠出现高血糖、高乳酸血症和低钙血症。葡萄糖和乳酸的峰值增加在治疗后15分钟内出现，随后血浆钙水平下降较慢。为了确定这些作用的剂量反应特征，给禁食动物注射0.005微克至500微克（64皮摩尔/千克至6.4微摩尔/千克）的胰岛淀粉样多肽。高血糖、高乳酸血症和低钙血症作用的半数有效剂量（ED50）分别为155、16.9和190纳摩尔/千克，葡萄糖最大增加6.27毫摩尔/升，乳酸最大增加1.85毫摩尔/升，钙最大减少0.37毫摩尔/升。禁食小鼠中外源性胰岛淀粉样多肽在循环中的估计半衰期（t1/2）为5.0分钟。这些结果表明胰岛淀粉样多肽在小鼠中具有生物活性。动力学数据预测，外源性胰岛淀粉样多肽的生物有效剂量会导致血浆浓度与先前报道的内源性激素的病理生理浓度相当。
