Thermoregulatory and heat shock protein response deficits in cold
-exposed diabetic mice.
Matz, Jeannine M., Kathleen P. Lavoi, Paul N. Epstein, and Michael J.
Blake.
Department of Pharmacology and Toxicology, University of North
Dakota, Grand Forks, ND 58202
APStracts 2:0282R, 1995.
Cold-induced expression of heat shock proteins (HSPs) has been
suggested to facilitate thermogenesis in brown adipose tissue (BAT).
However, the regulation of this response and the mechanism supporting
this facilitation has not been established. Due to the significant
role of insulin in maintaining BAT thermogenesis, we employed a
transgenic mouse model of diabetes to investigate the regulation and
function of HSPs in BAT thermogenesis. These transgenic mice
overexpress a calmodulin minigene regulated by the rat insulin II
promotor resulting in severe diabetes characterized by elevated blood
glucose and glucagon that coincides with reduced serum and pancreatic
insulin. Body temperature (Tb) of diabetic mice dropped significantly
faster during a 3 hour cold exposure (6 C) than Tb of similarly
treated control littermates. Cold exposure resulted in increased
levels of constitutive and inducible HSP70 transcripts in control
mice, but only constitutive HSP70 mRNA transcripts were induced in
diabetic mice. Diabetes did not affect UCP induction, but cold
-induced expression of members of other HSP families was reduced.
Correspondingly, heat shock regulatory factors were not activated in
diabetic mice even though these factors were present. Phenylephrine
induced HSP70 expression in control and diabetic animals indicating
that [alpha]-receptor-coupled HSP induction remained intact in BAT of
diabetic mice. Insulin replacement restored the Tb response of
diabetic mice as well as the HSP response. From these results it is
clear that physiologic signals that regulate cold-induced activation
of BAT also regulate HSP expression in this tissue. This diabetic
model provides a novel system in which the HSP response to cold has
been selectively knocked-out, making it a useful tool for the study
of HSP regulation and function in BAT.
Received 7 March 1995; accepted in final form 28 September 1995.
APS Manuscript Number R151-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95