4.6 Article

Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity

期刊

FRONTIERS IN PHYSIOLOGY
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2022.895118

关键词

glycerol; glucose; insulin; insulin resisitance; lipolysis; mathematical model

资金

  1. National Institutes of Health (NIH)
  2. Doris Duke Foundation [BIRCWH K12HD057022, NIDDK K23DK107871]
  3. Children's Hospital Colorado/Colorado School of Mines Collaborative Pilot Award [2015212]
  4. Mines Undergraduate Research Fellowship
  5. Boettcher Foundation
  6. Boettcher-Webb Warring grant
  7. National Science Foundation
  8. Nutrition and Obesity Research Core Pilot Grant [DMS 1853511]
  9. University of Colorado NIH CTSI protocol micro-grant [P30 DK048520]
  10. NIH/NCATS Colorado CTSA
  11. [UL1 TR001082]

向作者/读者索取更多资源

Insulin resistance occurs when more insulin is required to achieve the same effects, and this resistance may be tissue-specific. This study found that insulin acts more quickly on adipose tissue compared to muscle and liver, suggesting tissue-specific dynamics of insulin action in an insulin-resistant adolescent population.
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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