Expression of calmodulin gene is down-regulated in diabetic BB rats

Solomon S. Solomon, Marjorie R. Palazzolo, Stuart Green, Rajendra Raghow

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Abstract

In past studies, we have demonstrated that in streptozotocin-induced diabetic or spontaneously diabetic (BB) animal models, low Km cAMP phophodiesterase and calmodulin are decreased while a low MW inhibitor of calmodulin is increased. To extend these studies, we have determined the rate of [35S]-methionine incorporation into calmodulin in isolated fat cells from these diabetic animals, i.e. streptozotocin-induced diabetic and the BB rats, spontaneous diabetic rat, non-diabetic rat, and control. We found markedly decreased rates of synthesis of calmodulin in the fully diabetic BB rat. In order to investigate the mechanism of the reduced calmodulin biosynthesis, we probed poly A+ mRNA from control and diabetic rat livers with a calmodulin specific anti-sense oligonucleotide probe and found that the fully diabetic animals, streptozotocin-induced diabetic and genetically diabetic BB, contained markedly reduced levels of calmodulin transcripts. Thus, both calmodulin protein and its putative mRNA are decreased in diabetic rat liver. We believe that in uncontrolled diabetes, the observed elevation in the levels of cyclic AMP in plasma and tissue results in part from decreased activity of phosphodiesterase. The insulin-sensitive phosphodiesterase appears to be regulated by calmodulin. We hypothesize that cyclic AMP phosphodiesterase inactivation in diabetes results in part from insulin insufficiency and to a less well-defined genetic lesion leading to calmodulin down-regulation.

Original languageEnglish (US)
Pages (from-to)1007-1012
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume168
Issue number3
DOIs
StatePublished - May 16 1990

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Inbred BB Rats
Calmodulin
Rats
Genes
Gene Expression
Phosphoric Diester Hydrolases
Streptozocin
Animals
Medical problems
Liver
Cyclic AMP
Insulin
Messenger RNA
Oligonucleotide Probes
Antisense Oligonucleotides
Biosynthesis
Adipocytes
Methionine
Down-Regulation
Animal Models

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Expression of calmodulin gene is down-regulated in diabetic BB rats. / Solomon, Solomon S.; Palazzolo, Marjorie R.; Green, Stuart; Raghow, Rajendra.

In: Biochemical and Biophysical Research Communications, Vol. 168, No. 3, 16.05.1990, p. 1007-1012.

Research output: Contribution to journalArticle

Solomon, Solomon S. ; Palazzolo, Marjorie R. ; Green, Stuart ; Raghow, Rajendra. / Expression of calmodulin gene is down-regulated in diabetic BB rats. In: Biochemical and Biophysical Research Communications. 1990 ; Vol. 168, No. 3. pp. 1007-1012.
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