Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic, Rochester, MN, USA.
Department of Information Engineering, University of Padova, Padova, Italy.
J Clin Endocrinol Metab. 2021 May 13;106(6):1702-1709. doi: 10.1210/clinem/dgab100.
Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action.
We studied 29 nondiabetic subjects on two occasions. On 1 occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day, we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used approximate entropy to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies.
In univariate analysis, basal insulin secretion (R2 = 0.16) and insulin pulse amplitude (R2 = 0.09) correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex, and weight, these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis) or to stimulate glucose disappearance.
Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in nondiabetic humans.
在 2 型糖尿病等以胰岛素抵抗为特征的疾病中，脉冲式胰岛素分泌受损。这导致人们提出这样的假设，即胰岛素脉冲的变化会直接损害胰岛素信号。我们试图在人类中研究胰岛素脉冲特征对胰岛素作用的影响，假设脉冲幅度或频率的降低与肝胰岛素作用受损有关。
我们在两次不同的时间点研究了 29 名非糖尿病患者。在一次实验中，通过 1 次正葡萄糖钳夹实验测量肝和外周胰岛素作用。使用氘水法来估计糖异生对内源性葡萄糖生成的贡献。在另一天的研究中，我们利用空腹时频繁取样的外周 C 肽浓度的非参数随机反卷积来重建门静脉胰岛素分泌。除了测量基础和脉冲式胰岛素分泌外，我们还使用近似熵来测量有序性，使用傅里叶变换来测量平均胰岛素脉冲频率和频率的离散度。
在单变量分析中，基础胰岛素分泌（R2=0.16）和胰岛素脉冲幅度（R2=0.09）与胰岛素诱导的糖异生抑制作用呈弱相关。然而，在调整年龄、性别和体重后，这些相关性不再显著。其他脉冲特征也与胰岛素抑制内源性葡萄糖生成（和糖异生）或刺激葡萄糖清除的能力无关。
总的来说，我们的数据表明，在非糖尿病患者中，独立于其他因素考虑的胰岛素脉冲特征与肝和外周胰岛素敏感性的测量值不相关。
