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Enhanced Diabetogenic Effect of Streptozotocin in Mice Overexpressing UCP‐3 in Skeletal Muscle
Author(s) -
WANG STEVEN,
CAWTHORNE MICHAEL A.,
CLAPHAM JOHN C.
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04269.x
Subject(s) - medicine , endocrinology , streptozotocin , skeletal muscle , ucp3 , insulin , diabetes mellitus , transgene , genetically modified mouse , chemistry , biology , uncoupling protein , biochemistry , adipose tissue , gene , brown adipose tissue
A bstract : Diabetic patients exhibit varying degrees of increased muscle UCP‐3 expression in skeletal muscle and, in rodents, the pancreatoxin streptozotocin (STZ) upregulates UCP‐3 mRNA in skeletal and cardiac muscles. We have investigated the development of STZ‐induced diabetes in transgenic mice overexpressing UCP‐3 in skeletal muscle in order to provide further insight on the functional role of muscle UCP‐3. UCP‐3 transgenic mice treated with STZ (UCP3‐STZ) showed a significant increase in blood glucose concentration 3 days after the last dose of STZ with a progressive induction of diabetes, attaining blood glucose concentrations of 24.7 ± 1.5 mmol/L on day 17. Wild‐type mice treated with STZ (WT‐STZ) only started to show an increase in blood glucose concentration 6 days after the last dose of STZ and peaked on day 17 at a lower concentration than in the UCP‐STZ mice. The pancreatic insulin content of UCP‐3 control mice (UCP3‐CON) was decreased relative to wild‐type control mice (WT‐CON), and STZ reduced the total pancreatic insulin content by 72% in WT‐STZ mice and by 88% in UCP3‐STZ mice. In an insulin tolerance test, blood glucose concentrations declined more in the UCP‐3 transgenic mice than in the wild‐type mice. Mice overexpressing UCP‐3 in skeletal muscle have a lower pancreatic insulin content, but tend to be more insulin‐sensitive. These twin actions result in an increased susceptibility to STZ‐induced diabetes in UCP‐3 transgenic mice.