Inhibitor of calmodulin and cAMP phosphodiesterase activity in BB rats

• Published in: Diabetes (New York, N.Y.) Vol. 36; no. 2; pp. 210 - 215
• Main Authors: Solomon, S. S., Steiner, M. S., Little, W. L., Rao, R. H., Sanders, L. L., Palazzolo, M. R.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-02-1987
• DOI: 10.2337/diabetes.36.2.210
• EISSN: 1939-327X; 0012-1797
• ISSN: 0012-1797

Inhibitor of calmodulin and cAMP phosphodiesterase activity in BB rats.
S S Solomon ,
M S Steiner ,
W L Little ,
R H Rao ,
L L Sanders and
M R Palazzolo
Abstract
Diabetes mellitus in humans is associated with increased plasma and tissue levels of cAMP and decreased cAMP phosphodiesterase
(PDE) activity. Calmodulin (CM) is a low-molecular-weight protein essential for activation of cAMP PDE. The inhibitor (INH)
is a low-molecular-weight substance that inhibits the activity of CM in multiple systems, including PDE. Spontaneously diabetic
BB rats (SDR) and their nondiabetic littermates (NDR) were used in this study. Holtzman rats were rendered diabetic by streptozocin
(STZ). STZ-induced diabetic rats (STZ-DR) and BB rats were studied with and without the benefit of insulin therapy. Calmodulin
was assayed both by bioassay and by specific radioimmunoassay. The inhibitor was bioassayed by its ability to inhibit CM-activated
PDE. Results showed that both spontaneous and STZ-induced diabetes are associated with a decrease in activity of the low-Michaelis
constant (Km) cAMP PDE in the liver (39%, SDR; 70% STZ-DR). Calmodulin activity was also decreased in the livers of both animals
(13%, SDR; 68%, STZ-DR). Similar data were obtained for NDRs. The inhibitor, on the other hand, was increased in the livers
of untreated SDRs and STZ-DRs (155%, SDR; 125%, STZ-DR). No change was noted for NDRs. All these changes were restored toward
normal after treatment with insulin. These data suggest that in diabetes the defect in the cAMP PDE-CM-INH system is demonstrated
in both an environmental model, as illustrated by STZ-DRs, and a genetic model, as shown by SDRs and NDRs. The inhibitor activity,
however, is not changed significantly in NDRs. We speculate that the inhibitor activity plays a role in dictating whether
the genetic NDR will or will not become clinically diabetic.