Address for correspondence: Steven Wang, Clore Laboratory, University of Buckingham, Buckingham MK18 1EG, United Kingdom. Voice: +44-1280-820242; fax: +44-1280-820261.
steven.wang{at}buckingham.ac.uk
cPresent address: Cell Biology and Biochemistry, AstraZeneca R&D Mölndal, Pepparedsleden 1, SE431 83 Mölndal, Sweden.
Ann. N.Y. Acad. Sci. 967: 112-119 (2002).
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.
