Division of Endocrinology, Diabetes & MetabolismEndocrine Research Unit, Mayo Clinic, College of Medicine and Science, Rochester, Minnesota, USA.
Biomedical Engineering and Physiology Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, USA.
Physiol Rep. 2022 Jul;10(13):e15380. doi: 10.14814/phy2.15380.
Abnormal postprandial suppression of glucagon in Type 2 diabetes (T2DM) has been attributed to impaired insulin secretion. Prior work suggests that insulin and glucagon show an inverse coordinated relationship. However, dysregulation of α-cell function in prediabetes occurs early and independently of changes in β-cells, which suggests insulin having a less significant role on glucagon control. We therefore, sought to examine whether hepatic vein hormone concentrations provide evidence to further support the modulation of glucagon secretion by insulin. As part of a series of experiments to measure the effect of diabetes-associated genetic variation in TCF7L2 on islet cell function, hepatic vein insulin and glucagon concentrations were measured at 2-minute intervals during fasting and a hyperglycemic clamp. The experiment was performed on 29 nondiabetic subjects (age = 46 ± 2 years, BMI 28 ± 1 Kg/m ) and enabled post-hoc analysis, using Cross-Correlation and Cross-Approximate Entropy (Cross-ApEn) to evaluate the interaction of insulin and glucose. Mean insulin concentrations rose from fasting (33 ± 4 vs. 146 ± 12 pmol/L, p < 0.01) while glucagon was suppressed (96 ± 8 vs. 62 ± 5 ng/L, p < 0.01) during the clamp. Cross-ApEn was used to measure pattern reproducibility in the two hormones using glucagon as control mechanism (0.78 ± 0.03 vs. 0.76 ± 0.03, fasting vs. hyperglycemia) and using insulin as a control mechanism (0.78 ± 0.02 vs. 0.76 ± 0.03, fasting vs. hyperglycemia). Values did not differ between the two scenarios. Cross-correlation analysis demonstrated a small in-phase coordination between insulin and glucagon concentrations during fasting, which inverted during hyperglycemia. This data suggests that the interaction between the two hormones is not driven by either. On a minute-to-minute basis, direct control and secretion of glucagon is not mediated (or restrained) by insulin.
2 型糖尿病（T2DM）患者餐后胰高血糖素抑制异常归因于胰岛素分泌受损。先前的研究表明，胰岛素和胰高血糖素呈反向协调关系。然而，在β细胞发生变化之前，糖尿病前期的α细胞功能失调就已经发生，这表明胰岛素对胰高血糖素的控制作用不那么显著。因此，我们试图研究肝静脉激素浓度是否能提供进一步支持胰岛素调节胰高血糖素分泌的证据。作为一系列实验的一部分，该实验旨在测量 TCF7L2 相关的糖尿病遗传变异对胰岛细胞功能的影响，在空腹和高血糖钳夹期间，以 2 分钟为间隔测量肝静脉胰岛素和胰高血糖素浓度。该实验在 29 名非糖尿病受试者（年龄=46±2 岁，BMI 28±1kg/m ）中进行，并使用互相关和互近似熵（Cross-ApEn）进行事后分析，以评估胰岛素和葡萄糖的相互作用。平均胰岛素浓度从空腹时的（33±4 对 146±12pmol/L，p<0.01）升高，而在钳夹期间胰高血糖素被抑制（96±8 对 62±5ng/L，p<0.01）。使用胰高血糖素作为对照机制（0.78±0.03 对 0.76±0.03，空腹对高血糖）和使用胰岛素作为对照机制（0.78±0.02 对 0.76±0.03，空腹对高血糖），使用 Cross-ApEn 测量两种激素的模式再现性。两种情况下的值没有差异。互相关分析表明，在空腹期间，胰岛素和胰高血糖素浓度之间存在小的同相协调，而在高血糖期间则发生反转。这表明两种激素之间的相互作用不是由其中任何一种驱动的。从每分钟的角度来看，胰高血糖素的直接控制和分泌不受胰岛素的调节（或抑制）。
