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Lu 2018 Cell Discov
Additional label 2018-12  +
Coupling states OXPHOS  + , ET  +
Diseases Diabetes  +
Has abstract Insulin is critical for glucose homeostasi
Insulin is critical for glucose homeostasis, and insulin deficiency or resistance leads to the development of diabetes. Recent evidence suggests that diabetes can be remitted independent of insulin. However, the underlying mechanism remains largely elusive. In this study, we utilized metabolic surgery as a tool to identify the non-insulin determinant mechanism. Here, we report that the most common metabolic surgery, Roux-en-Y gastric bypass (RYGB), reduced insulin production but persistently maintained euglycemia in healthy Sprague-Dawley (SD) rats and C57 mice. This reduction in insulin production was associated with RYGB-mediated inhibition of pancreatic preproinsulin and polypyrimidine tract-binding protein 1. In addition, RYGB also weakened insulin sensitivity that was evaluated by hyperinsulinemic-euglycemic clamp test and downregulated signaling pathways in insulin-sensitive tissues. The mechanistic evidence suggests that RYGB predominately shifted the metabolic profile from glucose utilization to fatty acid oxidation, enhanced the energy expenditure and activated multiple metabolic pathways through reducing gut energy uptake. Importantly, the unique effect of RYGB was extended to rats with islet disruption and patients with type 2 diabetes. These results demonstrate that compulsory rearrangement of the gastrointestinal tract can initiate non-insulin determinant pathways to maintain glucose homeostasis. Based on the principle of RYGB action, the development of a noninvasive intervention of the gastrointestinal tract is a promising therapeutic route to combat disorders characterized by energy metabolism dysregulation.
erized by energy metabolism dysregulation.  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30275974 Open Access]  +
Has title Lu Z, Wei X, Sun F, Zhang H, Gao P, Pu Y, Wang A, Chen J, Tong W, Li Q, Zhou X, Yan Z, Zheng H, Yang G, Huang Y, Liu D, Zhu Z (2018) Non-insulin determinant pathways maintain glucose homeostasis upon metabolic surgery. Cell Discov 4:58.  +
Instrument and method Oxygraph-2k  +
Mammal and model Rat  +
MiP area Respiration  +
Pathways F  + , N  + , ROX  +
Preparation Isolated mitochondria  +
Tissue and cell Skeletal muscle  + , Liver  +
Was published by MiPNetLab CN Chongqing Zhu Z +
Was published in journal Cell Discov +
Was published in year 2018  +
Was written by Lu Z + , Wei X + , Sun F + , Zhang H + , Gao P + , Pu Y + , Wang A + , Chen J* + , Tong W + , Li Q + , Zhou X + , Yan Z + , Zheng H* + , Yang G + , Huang Y + , Liu D + , Zhu Z +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:41:45, 29 July 2019  +
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