Insulin
Resistance, Heat Shock Proteins and Metabolic Disease
Insulin resistance, an insufficient signal of the insulin
receptor to evoke its´ full strength of effects on glucose,
lipids and other metabolites, is a major cause of type 2
diabetes and the metabolic syndrome. Inflammatory and
metabolic stress signals, in turn, provoke insulin
resistance (Hotamisligil and Spiegelman, Diabetes, Vol 43,
pp. 1271, 1994). In consequence, modulators alleviating such
stress signals are of great potential in the treatment of
metabolic disorders. The Induction of heat shock proteins
has emerged as a promising novel approach to modulate
inflammatory and insulin signaling in a beneficial way.
Up-regulation of heat shock protein HSP-72 levels by either
way - heat shock, transgenic expression or pharmacological
treatment with the compound BGP-15- protects against obesity
induced insulin resistance in mice (Chung et al., PNAS
Vol.205, pp.1739, 2008). This protection was tightly
associated with the inhibition of inflammatory and elevation
of insulin signals. These effects translate into an improved
glycemic control in animal models of type 2 diabetes and
other states of insulin resistance (-> "Lead molecule
BGP-15, pharmacology").
In a clinical setting, insulin resistance in human subjects
due to either obesity or use of atypical anti-psychotic
drugs could be overcome by treatment with heat-shock inducer
BGP-15 (-> "Products"). Interestingly, heat treatment in a
hot tub has been shown to improve gylcemic control in
patients with type 2 diabetes (Hooper, P.L., N Engl J Med,
Vol. 341, p. 924-25, 1999). This finding lends further
suggestive support to the concept that pharmacological
induction of a heat shock response in states of insulin
resistance may be beneficial.
