isiKnock: <i>in silico</i> knockouts in biochemical pathways

Scheidel, Jennifer; Giese, Heiko; Schweizer, Börje; Amstein, Leonie; Ackermann, Jörg; Koch, Ina

doi:10.1101/313858

Cited by 1 publication

(1 citation statement)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such studies are conducted to assess the functional roles of the genes upon their loss on the regulation of the system under study. The Petri nets‐based KO analysis and methodologies have been described previously in [ 105 , 106 ]. We modelled a gene KO scenario of ANGPTL8 similar to the in‐vivo experiments of [ 12 ] to scrutinise the role of ANGPTL8 in insulin resistance.…”

Section: Resultsmentioning

confidence: 99%

Deciphering the expression dynamics of ANGPTL8 associated regulatory network in insulin resistance using formal modelling approaches

et al. 2020

View full text Add to dashboard Cite

ANGPTL8 is a recently identified novel hormone which regulates both glucose and lipid metabolism. The increase in ANGPTL8 during compensatory insulin resistance has been recently reported to improve glucose tolerance and a part of cytoprotective metabolic circuit. However, the exact signalling entities and dynamics involved in this process have remained elusive. Therefore, the current study was conducted with a specific aim to model the regulation of ANGPTL8 with emphasis on its role in improving glucose tolerance during insulin resistance. The main contribution of this study is the construction of a discrete model (based on kinetic logic of René Thomas) and its equivalent Stochastic Petri Net model of ANGPTL8 associated Biological Regulatory Network (BRN) which can predict its dynamic behaviours. The predicted results of these models are in‐line with the previous experimental observations and provide comprehensive insights into the signalling dynamics of ANGPTL8 associated BRN. The authors’ results support the hypothesis that ANGPTL8 plays an important role in supplementing the insulin signalling pathway during insulin resistance and its loss can aggravate the pathogenic process by quickly leading towards Diabetes Mellitus. The results of this study have potential therapeutic implications for treatment of Diabetes Mellitus and are suggestive of its potential as a glucose‐lowering agent.

show abstract

Section: Resultsmentioning

confidence: 99%