Role of insulin in pancreatic microcirculatory oxygen profile and bioenergetics
作者机构：Institute of MicrocirculationDiabetes Research CenterChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Laboratory of Electron MicroscopyUltrastructural Pathology CenterPeking University First HospitalBeijing 100005China
出 版 物：《World Journal of Diabetes》 (世界糖尿病杂志（英文版）（电子版）)
年 卷 期：2022年第13卷第9期
页 面：765-775页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 10[医学]
基 金：Supported by the Beijing Municipal Natural Science Foundation,No.7212068 the National Natural Science Foundation of China,No.81900747
主 题：Diabetes mellitus Glucotoxicity Endothelial cells Microcirculation Mitochondria Bioenergetics
摘 要：BACKGROUND The pancreatic islet microcirculation adapts its metabolism to cope with limited oxygen availability and nutrient *** diabetes,the balance between oxygen delivery and consumption is *** has been proven to exert complex actions promoting the maintenance of homeostasis of the pancreas under *** To test the hypothesis that insulin administration can improve the integrated pancreatic microcirculatory oxygen profile and *** The pancreatic microcirculatory partial oxygen pressure(PO_(2)),relative hemoglobin(rHb)and hemoglobin oxygen saturation(SO_(2))were evaluated in nondiabetic,type 1 diabetes mellitus(T1DM),and insulin-treated mice.A threedimensional framework was generated to visualize the microcirculatory oxygen *** changes in the microvasculature were examined using transmission electron *** 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).RESULTS Significantly lower PO_(2),rHb,and SO_(2) values were observed in T1DM mice than in nondiabetic *** administration ameliorated the streptozotocin-induced decreases in these microcirculatory oxygen parameters and improved the mitochondrial ultrastructural abnormalities in *** profiling revealed that the IMECs did not have spare respiratory ***-treated IMECs exhibited significantly greater basal respiration than glucotoxicity-exposed IMECs(P0.05).An energy map revealed increased energetic metabolism in insulin-treated IMECs,with significantly increased ATP production,non-mitochondrial respiration,and oxidative metabolism(all P0.05).Significant negative correlations were revealed between microcirculatory SO_(2) and bioenergetic *** Glucotoxicity deteriorates the integrated pancreatic microcirculatory oxygen profil
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