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A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance

Author

Listed:
  • Gang Zhao

    (Helmholtz Centre for Infection Research)

  • Dagmar Wirth

    (Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research
    Hannover Medical School)

  • Ingo Schmitz

    (Helmholtz Centre for Infection Research
    Otto-von-Guericke University)

  • Michael Meyer-Hermann

    (Helmholtz Centre for Infection Research
    Technische Universität Braunschweig)

Abstract

Physiological insulin secretion exhibits various temporal patterns, the dysregulation of which is involved in diabetes development. We analyzed the impact of first-phase and pulsatile insulin release on glucose and lipid control with various hepatic insulin signaling networks. The mathematical model suggests that atypical protein kinase C (aPKC) undergoes a bistable switch-on and switch-off, under the control of insulin receptor substrate 2 (IRS2). The activation of IRS1 and IRS2 is temporally separated due to the inhibition of IRS1 by aPKC. The model further shows that the timing of aPKC switch-off is delayed by reduced first-phase insulin and reduced amplitude of insulin pulses. Based on these findings, we propose a sequential model of postprandial hepatic control of glucose and lipid by insulin, according to which delayed aPKC switch-off contributes to selective hepatic insulin resistance, which is a long-standing paradox in the field.

Suggested Citation

  • Gang Zhao & Dagmar Wirth & Ingo Schmitz & Michael Meyer-Hermann, 2017. "A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01627-9
    DOI: 10.1038/s41467-017-01627-9
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