Queueing theory model of mTOR complexes' impact on Akt-mediated adipocytes response to insulin

PLoS One. 2022 Dec 27;17(12):e0279573. doi: 10.1371/journal.pone.0279573. eCollection 2022.

Abstract

A queueing theory based model of mTOR complexes impact on Akt-mediated cell response to insulin is presented in this paper. The model includes several aspects including the effect of insulin on the transport of glucose from the blood into the adipocytes with the participation of GLUT4, and the role of the GAPDH enzyme as a regulator of mTORC1 activity. A genetic algorithm was used to optimize the model parameters. It can be observed that mTORC1 activity is related to the amount of GLUT4 involved in glucose transport. The results show the relationship between the amount of GAPDH in the cell and mTORC1 activity. Moreover, obtained results suggest that mTORC1 inhibitors may be an effective agent in the fight against type 2 diabetes. However, these results are based on theoretical knowledge and appropriate experimental tests should be performed before making firm conclusions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Insulin* / metabolism
  • Insulin, Regular, Human / metabolism
  • Mechanistic Target of Rapamycin Complex 1 / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Insulin
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Insulin, Regular, Human
  • Glucose
  • Glucose Transporter Type 4
  • MTOR protein, human