Utilization of fluorescence tracer in hyperinsulinemic-euglycemic clamp test in mice.
The hyperinsulinemic-euglycemic clamp test is considered to be a gold standard for the evaluation of insulin sensitivity. Here, a new version of the clamp test that used the fluorescence tracer 2-NBDG was tested. C57BL/6J mice were induced insulin resistant (IR) with a high-calorie diet. Rosiglitazone was administrated to IR mice and diabetic db/db mice. Insulin resistance was estimated with the oral glucose tolerance test (OGTT), the insulin tolerance test (ITT), the serum insulin level and the homeostasis model assessment of insulin resistance (HOMA-IR), and then confirmed by the hyperinsulinemic-euglycemic clamp test with 2-NBDG. The 2-NBDG content was measured by the fluorescence intensity. The characteristics of insulin resistance were shown remarkably with the increased values of serum insulin and HOMA-IR in IR mice, and with the results from OGTT and ITT in both IR and db/db mice. In the hyperinsulinemic-euglycemic clamp test, the glucose infusion rate and amount of 2-NBDG taken up into the liver, adipose, and skeletal muscle were decreased significantly in IR mice and db/db mice, respectively. The clearing rates of 2-NBDG from the circulation were much slower in both mouse models. All markers were reversed significantly by rosiglitazone treatment. The results indicate that with the fluorescence tracer 2-NBDG, the hyperinsulinemic-euglycemic clamp test can be used to estimate insulin sensitivity in vivo.
Ye
Fei
F
Institute of Materia Medica, Chinese Academy of Medical Sciences & Perking Union Medical College, 1, Xian Nong Tan Street, Beijing 100050, China. yefei@imm.ac.cn
Tao
Rongya
R
Cong
Weina
W
Tian
Jinying
J
Liu
Qian
Q
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000032:analysis; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis*; D015309:Glucose Clamp Technique / Q000379:methods*; D006946:Hyperinsulinism / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity
D001786:Blood Glucose; D005456:Fluorescent Dyes; D003847:Deoxyglucose; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose