Pulsatile hyperglycemia increases insulin secretion but not pancreatic β-cell mass in intrauterine growth-restricted fetal sheep.
Pulsatile hyperglycemia increases insulin secretion but not pancreatic β-cell mass in intrauterine growth-restricted fetal sheep.
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DOI：
10.1017/s2040174418000417
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发表时间：
2018-10
影响因子：
1.7
通讯作者：
Rozance PJ
中科院分区：
文献类型：
--
作者：
Boehmer BH;Brown LD;Wesolowski SR;Hay WW;Rozance PJ
β细胞发育和胰岛素分泌受损是宫内生长受限（IUGR）胎儿的特征。正常生长的妊娠晚期胎羊在发生脉动性高血糖（PHG） 7-10天后胰腺β细胞数量和胰岛素分泌增加。我们的目的是确定IUGR胎羊β细胞数量和胰岛素分泌是否也可以通过PHG增加，或者IUGR胎羊β细胞是否对PHG没有反应能力。在双胎妊娠（n = 7）慢性胎盘功能不全产生IUGR后，对胎儿进行PHG输注，包括60分钟，高速率，脉冲输注葡萄糖，每天三次，另外持续，低速率输注葡萄糖，以防止脉冲之间的葡萄糖浓度下降或对照盐水输注。将PHG胎儿与双胞胎IUGR胎儿进行比较，后者接受生理盐水输注7天。在输注期间，脉冲葡萄糖输注使胎儿动脉葡萄糖浓度平均增加83%。输注7天后，两组均采用方波胎儿高血糖钳测量胰岛素分泌。在方波高血糖钳夹的前20分钟内，PHG胎儿的胰岛素浓度升高速度比生理盐水胎儿快44% （P < 0.05）。各组胰岛大小、胰岛及胰岛胰岛素+面积、β细胞质量差异无统计学意义（P < 0.23）。慢性PHG增加早期胰岛素分泌以应对急性高血糖，表明IUGR胎儿β细胞对慢性PHG有功能反应。
Impaired β-cell development and insulin secretion are characteristic of intrauterine growth-restricted (IUGR) fetuses. In normally grown late gestation fetal sheep pancreatic β-cell numbers and insulin secretion are increased by 7–10 days of pulsatile hyperglycemia (PHG). Our objective was to determine if IUGR fetal sheep β-cell numbers and insulin secretion could also be increased by PHG or if IUGR fetal β-cells do not have the capacity to respond to PHG. Following chronic placental insufficiency producing IUGR in twin gestation pregnancies (n = 7), fetuses were administered a PHG infusion, consisting of 60 min, high rate, pulsed infusions of dextrose three times a day with an additional continuous, low-rate infusion of dextrose to prevent a decrease in glucose concentrations between the pulses or a control saline infusion. PHG fetuses were compared with their twin IUGR fetus, which received a saline infusion for 7 days. The pulsed glucose infusion increased fetal arterial glucose concentrations an average of 83% during the infusion. Following the 7-day infusion, a square-wave fetal hyperglycemic clamp was performed in both groups to measure insulin secretion. The rate of increase in fetal insulin concentrations during the first 20 min of a square-wave hyperglycemic clamp was 44% faster in the PHG fetuses compared with saline fetuses (P < 0.05). There were no differences in islet size, the insulin+ area of the pancreas and of the islets, and β-cell mass between groups (P > 0.23). Chronic PHG increases early phase insulin secretion in response to acute hyperglycemia, indicating that IUGR fetal β-cells are functionally responsive to chronic PHG.