Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity.
Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity.
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DOI：
10.3389/fphys.2022.895118
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发表时间：
2022
影响因子：
4
通讯作者：
Behn, Cecilia Diniz
中科院分区：
文献类型：
--
作者：
Hampton, Griffin S. S.;Bartlette, Kai;Nadeau, Kristen J. J.;Cree-Green, Melanie;Behn, Cecilia Diniz
在健康状况下，胰腺通过释放胰岛素来响应葡萄糖挑战。胰岛素抑制脂肪组织中的脂解作用，从而降低血浆甘油浓度，并通过在肌肉和肝脏中的作用调节血浆葡萄糖浓度。胰岛素抵抗（IR）发生在需要更多胰岛素才能达到相同效果时，并且IR可能是组织特异性的。IR出现在青春期，是由于高浓度的生长激素，并因青年发病的肥胖而恶化。脂肪、肝脏和肌肉组织在多相高胰岛素-正常血糖（HE）钳夹中对胰岛素表现出明显的剂量依赖性反应，但HE钳夹方案并未解决组织特异性胰岛素反应动力学的潜在差异。胰岛素反应动力学的变化将改变对葡萄糖挑战的血糖控制。为了研究胰岛素作用于脂肪组织的动力学，我们发明了一种新的微分器基于方程的模型，描述了在肥胖和IR的女性青少年口服葡萄糖耐量试验期间甘油浓度和胰岛素作用的耦合动力学。我们将这些动力学与胰岛素作用于肌肉和肝脏的动力学进行了比较，这些动力学是通过应用于在相同的协议。我们发现，胰岛素对甘油的作用提前约67分钟达到峰值（p < 0.001），并且与胰岛素对葡萄糖的作用相比，胰岛素对甘油的作用更接近血浆胰岛素的动力学，如通过代表胰岛素对葡萄糖和甘油作用的时间常数的参数所评估的（p < 0.001）。这些发现表明，胰岛素作用的动力学在我们的IR青少年人群中显示出组织特异性差异，与肌肉和肝脏相比，脂肪组织对胰岛素的反应更快。对胰岛素作用的组织特异性动力学的更好理解可能为具有不同代谢表型的患者人群中代谢疾病的进展提供新的见解。
Under healthy conditions, the pancreas responds to a glucose challenge by releasing insulin. Insulin suppresses lipolysis in adipose tissue, thereby decreasing plasma glycerol concentration, and it regulates plasma glucose concentration through action in muscle and liver. Insulin resistance (IR) occurs when more insulin is required to achieve the same effects, and IR may be tissue-specific. IR emerges during puberty as a result of high concentrations of growth hormone and is worsened by youth-onset obesity. Adipose, liver, and muscle tissue exhibit distinct dose-dependent responses to insulin in multi-phase hyperinsulinemic-euglycemic (HE) clamps, but the HE clamp protocol does not address potential differences in the dynamics of tissue-specific insulin responses. Changes to the dynamics of insulin responses would alter glycemic control in response to a glucose challenge. To investigate the dynamics of insulin acting on adipose tissue, we developed a novel differential-equations based model that describes the coupled dynamics of glycerol concentrations and insulin action during an oral glucose tolerance test in female adolescents with obesity and IR. We compared these dynamics to the dynamics of insulin acting on muscle and liver as assessed with the oral minimal model applied to glucose and insulin data collected under the same protocol. We found that the action of insulin on glycerol peaks approximately 67 min earlier (p < 0.001) and follows the dynamics of plasma insulin more closely compared to insulin action on glucose as assessed by the parameters representing the time constants for insulin action on glucose and glycerol (p < 0.001). These findings suggest that the dynamics of insulin action show tissue-specific differences in our IR adolescent population, with adipose tissue responding to insulin more quickly compared to muscle and liver. Improved understanding of the tissue-specific dynamics of insulin action may provide novel insights into the progression of metabolic disease in patient populations with diverse metabolic phenotypes.
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影响因子：
16.2
作者：
通讯作者：
--
影响因子：
3.4
作者：
Cree-Green M;Cai N;Thurston JE;Coe GV;Newnes L;Garcia-Reyes Y;Baumgartner AD;Pyle L;Nadeau KJ
通讯作者：
Nadeau KJ
影响因子：
3.5
作者：
Ajmera, I;Swat, M;Laibe, C;Le Novere, N;Chelliah, V
通讯作者：
Chelliah, V
DOI：
10.1152/ajpendo.1999.276.2.e233
发表时间：
1999-02-01
影响因子：
5.1
作者：
Coppack, SW;Persson, M;Miles, JM
通讯作者：
Miles, JM
影响因子：
2.6
作者：
Behn, Cecilia Diniz;Jin, Eunsook S.;Cree-Green, Melanie
通讯作者：
Cree-Green, Melanie