Zarrin M, Wellnitz O, Bruckmaier R M
Veterinary Physiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland; Department of Animal Science, Agriculture Faculty, Yasouj University, 75918-74831, Yasouj, I. R. Iran.
Veterinary Physiology, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Domest Anim Endocrinol. 2015 Apr;51:74-7. doi: 10.1016/j.domaniend.2014.11.004. Epub 2014 Nov 21.
Insulin and glucagon are glucoregulatory hormones that contribute to glucose homeostasis. Plasma insulin is elevated during normoglycemia or hyperglycemia and acts as a suppressor of glucagon secretion. We have investigated if and how insulin and glucose contribute to the regulation of glucagon secretion through long term (48 h) elevated insulin concentrations during simultaneous hypoglycemia or euglycemia in mid-lactating dairy cows. Nineteen Holstein dairy cows were randomly assigned to 3 treatment groups: an intravenous insulin infusion (HypoG, n = 5) to decrease plasma glucose concentrations (2.5 mmol/L), a hyperinsulinemic-euglycemic clamp to study effects of insulin at simultaneously normal glucose concentrations (EuG, n = 6) and a 0.9% saline infusion (NaCl, n = 8). Plasma glucose was measured at 5-min intervals, and insulin and glucose infusion rates were adjusted accordingly. Area under the curve of hourly glucose, insulin, and glucagon concentrations on day 2 of infusion was evaluated by analysis of variance with treatments as fixed effect. Insulin infusion caused an increase of plasma insulin area under the curve (AUC)/h in HypoG (41.9 ± 8.1 mU/L) and EuG (57.8 ± 7.8 mU/L) compared with NaCl (13.9 ± 1.1 mU/L; P < 0.01). Induced hyperinsulinemia caused a decline of plasma glucose AUC/h to 2.3 ± 0.1 mmol/L in HypoG (P < 0.01), whereas plasma glucose AUC/h remained unchanged in EuG (3.8 ± 0.2 mmol/L) and NaCl (4.1 ± 0.1 mmol/L). Plasma glucagon AUC/h was lower in EuG (84.0 ± 6.3 pg/mL; P < 0.05) and elevated in HypoG (129.0 ± 7.0 pg/mL; P < 0.01) as compared with NaCl (106.1 ± 5.4 pg/mL). The results show that intravenous insulin infusion induces elevated glucagon concentrations during hypoglycemia, although the same insulin infusion reduces glucagon concentrations at simultaneously normal glucose concentrations. Thus, insulin does not generally have an inhibitory effect on glucagon concentrations. If simultaneously glucose is low and insulin is high, glucagon is upregulated to increase glucose availability. Therefore, insulin and glucose are conjoint regulatory factors of glucagon concentrations in dairy cows, and the plasma glucose status is the key factor to decide if its concentrations are increased or decreased. This regulatory effect can be important for the maintenance of glucose homeostasis if insulin secretion is upregulated by other factors than high glucose such as high plasma lipid and protein concentrations at simultaneously low glucose.
胰岛素和胰高血糖素是有助于维持葡萄糖稳态的血糖调节激素。在正常血糖或高血糖期间，血浆胰岛素水平升高，并作为胰高血糖素分泌的抑制剂。我们研究了在泌乳中期奶牛同时发生低血糖或血糖正常时，胰岛素和葡萄糖是否以及如何通过长期（48小时）升高的胰岛素浓度来调节胰高血糖素的分泌。19头荷斯坦奶牛被随机分为3个处理组：静脉输注胰岛素（HypoG，n = 5）以降低血浆葡萄糖浓度（2.5 mmol/L），进行高胰岛素-正常血糖钳夹以研究胰岛素在同时正常葡萄糖浓度下的作用（EuG，n = 6），以及输注0.9%生理盐水（NaCl，n = 8）。每隔5分钟测量一次血浆葡萄糖，并相应调整胰岛素和葡萄糖输注速率。通过将处理作为固定效应的方差分析来评估输注第2天每小时葡萄糖、胰岛素和胰高血糖素浓度曲线下面积。与NaCl组（13.9±1.1 mU/L；P < 0.01）相比，HypoG组（41.9±8.1 mU/L）和EuG组（57.8±7.8 mU/L）胰岛素输注导致血浆胰岛素曲线下面积（AUC）/小时增加。诱导的高胰岛素血症使HypoG组血浆葡萄糖AUC/小时降至2.3±0.1 mmol/L（P < 0.01），而EuG组（3.8±0.2 mmol/L）和NaCl组（4.1±0.1 mmol/L）血浆葡萄糖AUC/小时保持不变。与NaCl组（106.1±5.4 pg/mL）相比，EuG组血浆胰高血糖素AUC/小时较低（84.0±6.3 pg/mL；P < 0.05），HypoG组升高（129.0±7.0 pg/mL；P < 0.01）。结果表明，静脉输注胰岛素在低血糖期间会诱导胰高血糖素浓度升高，尽管相同的胰岛素输注在同时正常葡萄糖浓度下会降低胰高血糖素浓度。因此，胰岛素一般对胰高血糖素浓度没有抑制作用。如果同时血糖低且胰岛素高，胰高血糖素会被上调以增加葡萄糖的可用性。因此，胰岛素和葡萄糖是奶牛胰高血糖素浓度的联合调节因子，血浆葡萄糖状态是决定其浓度升高或降低的关键因素。如果胰岛素分泌因高血浆脂质和蛋白质浓度等非高血糖因素而在同时低血糖时上调，这种调节作用对于维持葡萄糖稳态可能很重要。
