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

2.50
Hdl Handle:
http://hdl.handle.net/10033/621204
Title:
A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.
Authors:
Zhao, Gang; Wirth, Dagmar; Schmitz, Ingo; Meyer-Hermann, Michael ( 0000-0002-4300-2474 )
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.
Affiliation:
Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106, Germany.
Citation:
A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance. 2017, 8 (1):1362 Nat Commun
Journal:
Nature communications
Issue Date:
8-Nov-2017
URI:
http://hdl.handle.net/10033/621204
DOI:
10.1038/s41467-017-01627-9
PubMed ID:
29118381
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of the research group modell systems for infections and immunity (MSYS); publications of the AG system-oriented immunologyand infection research (SIME); publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorZhao, Gangen
dc.contributor.authorWirth, Dagmaren
dc.contributor.authorSchmitz, Ingoen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2017-12-13T09:08:17Z-
dc.date.available2017-12-13T09:08:17Z-
dc.date.issued2017-11-08-
dc.identifier.citationA mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance. 2017, 8 (1):1362 Nat Communen
dc.identifier.issn2041-1723-
dc.identifier.pmid29118381-
dc.identifier.doi10.1038/s41467-017-01627-9-
dc.identifier.urihttp://hdl.handle.net/10033/621204-
dc.description.abstractPhysiological 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.en
dc.typeArticleen
dc.contributor.departmentBraunschweiger Zentrum für Systembiologie, Rebenring 56, 38106, Germany.en
dc.identifier.journalNature communicationsen
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