A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance.
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Issue Date
2017-11-08
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Show full item recordAbstract
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.Citation
A mathematical model of the impact of insulin secretion dynamics on selective hepatic insulin resistance. 2017, 8 (1):1362 Nat CommunAffiliation
Braunschweiger Zentrum für Systembiologie, Rebenring 56, 38106, Germany.Journal
Nature communicationsPubMed ID
29118381Type
ArticleLanguage
enISSN
2041-1723ae974a485f413a2113503eed53cd6c53
10.1038/s41467-017-01627-9
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/