Basic Study
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World J Diabetes. Sep 15, 2022; 13(9): 765-775
Published online Sep 15, 2022. doi: 10.4239/wjd.v13.i9.765
Role of insulin in pancreatic microcirculatory oxygen profile and bioenergetics
Bing-Wei Li, Yuan Li, Xu Zhang, Sun-Jing Fu, Bing Wang, Xiao-Yan Zhang, Xue-Ting Liu, Qin Wang, Ai-Ling Li, Ming-Ming Liu
Bing-Wei Li, Yuan Li, Sun-Jing Fu, Bing Wang, Xiao-Yan Zhang, Xue-Ting Liu, Qin Wang, Ai-Ling Li, Ming-Ming Liu, Institute of Microcirculation, Diabetes Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
Xu Zhang, Laboratory of Electron Microscopy, Ultrastructural Pathology Center, Peking University First Hospital, Beijing 100005, China
Author contributions: Liu MM designed the experiments; Li BW, Li Y, Zhang X, Fu SJ, Wang B, Zhang XY, Liu XT, Wang Q and Li AL performed the experiments; Li BW, Li Y and Liu MM analyzed the data; Li BW and Liu MM wrote the manuscript; Liu MM made critical revisions to the article for important intellectual content; All authors discussed the results and approved the final version of the manuscript.
Supported by the Beijing Municipal Natural Science Foundation, No. 7212068; the National Natural Science Foundation of China, No. 81900747.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at the Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals, and approved by the Institutional Animal Care and Use Committee at the Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ming-Ming Liu, PhD, Research Scientist, Institute of Microcirculation, Diabetes Research Center, Chinese Academy of Medical Sciences & Peking Union Medical College, No.5 Dong Dan Third Alley, Dongcheng District, Beijing 100005, China. mingmingliu@imc.pumc.edu.cn
Received: April 29, 2022
Peer-review started: April 29, 2022
First decision: May 29, 2022
Revised: June 9, 2022
Accepted: August 25, 2022
Article in press: August 25, 2022
Published online: September 15, 2022
Processing time: 133 Days and 13.4 Hours
ARTICLE HIGHLIGHTS
Research background

The pancreatic islet microcirculation adapts its metabolism to cope with limited oxygen availability and nutrient delivery. In diabetes, the balance between oxygen delivery and consumption is impaired. Insulin has been proven to exert complex actions promoting the maintenance of homeostasis of the pancreas under glucotoxicity.

Research motivation

We tried to provide new insight into the relationship between pancreatic microcirculatory oxygen profile and microvascular endothelial mitochondrial metabolism.

Research objectives

To test the hypothesis that insulin administration can improve the integrated pancreatic microcirculatory oxygen profile and bioenergetics.

Research methods

A three-dimensional framework was generated to visualize the pancreatic microcirculatory oxygen profile. The microcirculatory partial oxygen pressure (PO2), relative hemoglobin (rHb) and hemoglobin oxygen saturation (SO2) were evaluated in nondiabetic, type 1 diabetes mellitus (T1DM), and insulin-treated mice. An Extracellular Flux Analyzer was used to detect the real-time changes in bioenergetics by measuring the oxygen consumption rate and extracellular acidification rate in islet microvascular endothelial cells (IMECs).

Research results

Insulin administration ameliorated the glucotoxicity-induced decreases in microcirculatory oxygen parameters (PO2, rHb, and SO2) and improved the mitochondrial ultrastructural abnormalities in IMECs. Insulin-treated IMECs exhibited significantly greater basal respiration than glucotoxicity-exposed IMECs. An energy map revealed increased energetic metabolism in insulin-treated IMECs, with significantly increased ATP production, non-mitochondrial respiration, and oxidative metabolism. Significant negative correlations were revealed between microcirculatory SO2 and bioenergetic parameters.

Research conclusions

Glucotoxicity deteriorates the integrated pancreatic microcirculatory oxygen profile and bioenergetics, but this deterioration can be reversed by insulin administration.

Research perspectives

Our understanding of the physiology and pathology of the pancreas islet microvascular endothelial cell in T1DM has been continually enhanced with the advancement of microcirculatory technology in parallel with rapidly developing bioenergetics that allows us to increase resolution and precision in our investigations.