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.

中文翻译：

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使用正式建模方法破译 ANGPTL8 相关调控网络在胰岛素抵抗中的表达动态。

ANGPTL8 是最近发现的一种调节葡萄糖和脂质代谢的新型激素。最近有报道称，代偿性胰岛素抵抗期间 ANGPTL8 的增加可改善葡萄糖耐量和细胞保护代谢回路的一部分。然而，这一过程中涉及的确切信号实体和动态仍然难以捉摸。因此，目前的研究旨在模拟 ANGPTL8 的调节，强调其在改善胰岛素抵抗期间的葡萄糖耐量中的作用。本研究的主要贡献是构建离散模型（基于 René Thomas 的动力学逻辑）及其等效的 ANGPTL8 相关生物调节网络（BRN）的随机 Petri 网模型，该模型可以预测其动态行为。这些模型的预测结果与之前的实验观察结果一致，并为 ANGPTL8 相关 BRN 的信号动力学提供了全面的见解。作者的结果支持这样的假设，即 ANGPTL8 在胰岛素抵抗期间在补充胰岛素信号通路中起重要作用，并且它的缺失会通过迅速导致糖尿病来加重发病过程。这项研究的结果对糖尿病的治疗具有潜在的治疗意义，并暗示其作为降糖剂的潜力。结果支持了这样的假设，即 ANGPTL8 在胰岛素抵抗期间在补充胰岛素信号通路中起重要作用，其缺失可通过迅速导致糖尿病加重发病过程。这项研究的结果对糖尿病的治疗具有潜在的治疗意义，并暗示其作为降糖剂的潜力。结果支持了这样的假设，即 ANGPTL8 在胰岛素抵抗期间在补充胰岛素信号通路中起重要作用，其缺失可通过迅速导致糖尿病加重发病过程。这项研究的结果对糖尿病的治疗具有潜在的治疗意义，并暗示其作为降糖剂的潜力。