Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity
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) occ...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2022.895118/full |
| _version_ | 1811221165324107776 |
|---|---|
| author | Griffin S. Hampton Kai Bartlette Kristen J. Nadeau Kristen J. Nadeau Melanie Cree-Green Melanie Cree-Green Cecilia Diniz Behn Cecilia Diniz Behn |
| author_facet | Griffin S. Hampton Kai Bartlette Kristen J. Nadeau Kristen J. Nadeau Melanie Cree-Green Melanie Cree-Green Cecilia Diniz Behn Cecilia Diniz Behn |
| author_sort | Griffin S. Hampton |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T07:53:16Z |
| format | Article |
| id | doaj.art-8a1fd7c811cb40e0a31eef250e77b008 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-04-12T07:53:16Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-8a1fd7c811cb40e0a31eef250e77b0082022-12-22T03:41:32ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2022-08-011310.3389/fphys.2022.895118895118Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesityGriffin S. Hampton0Kai Bartlette1Kristen J. Nadeau2Kristen J. Nadeau3Melanie Cree-Green4Melanie Cree-Green5Cecilia Diniz Behn6Cecilia Diniz Behn7Department of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United StatesDepartment of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United StatesDivision of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesLudeman Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDivision of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesLudeman Center for Women’s Health Research, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesDepartment of Applied Mathematics and Statistics, Colorado School of Mines, Golden, CO, United StatesDivision of Pediatric Endocrinology, University of Colorado Anschutz Medical Campus, Aurora, CO, United StatesUnder 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.https://www.frontiersin.org/articles/10.3389/fphys.2022.895118/fullglycerolglucoseinsulininsulin resisitancelipolysismathematical model |
| spellingShingle | Griffin S. Hampton Kai Bartlette Kristen J. Nadeau Kristen J. Nadeau Melanie Cree-Green Melanie Cree-Green Cecilia Diniz Behn Cecilia Diniz Behn Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity Frontiers in Physiology glycerol glucose insulin insulin resisitance lipolysis mathematical model |
| title | Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| title_full | Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| title_fullStr | Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| title_full_unstemmed | Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| title_short | Mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| title_sort | mathematical modeling reveals differential dynamics of insulin action models on glycerol and glucose in adolescent girls with obesity |
| topic | glycerol glucose insulin insulin resisitance lipolysis mathematical model |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2022.895118/full |
| work_keys_str_mv | AT griffinshampton mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT kaibartlette mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT kristenjnadeau mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT kristenjnadeau mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT melaniecreegreen mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT melaniecreegreen mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT ceciliadinizbehn mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity AT ceciliadinizbehn mathematicalmodelingrevealsdifferentialdynamicsofinsulinactionmodelsonglycerolandglucoseinadolescentgirlswithobesity |