Department of Pharmacology Faculty

Solomon S. Solomon M.D.

Solomon S. Solomon M.D.

Professor of Medicine
Chief, Endocrinology & Metabolism (VAMC)
Room BE123 Research Svc VAMC
Phone: 901-523-8990 ext. 7614


  • Harvard College, Cambridge, B.A. ,1958, Chemistry
  • University of Rochester Medical School, NY M.D., 1962, Medicine
  • New England Medical Center Internship, 1962-63, Straight Medicine
  • Boston City Hospital; Boston, MA , Residency, 1963-65
  • University of Washington, Seattle WA Postdoc., 1965-67, Endocrinology/Metabolism

Research Interests

Pathogenesis of Diabetes Mellitus: Studies of Insulin Action and Calmodulin

The objective of Dr. Solomon's research is to elucidate the molecular mechanisms involved in regulation of calmodulin ( CaM ) gene expression by insulin. Previously, Dr. Solomon has demonstrated that in streptozotocin-induced or spontaneously diabetic BB rats (BBSDR), the low Km cyclic AMP (cAMP) phosphodiesterase (PDE) and calmodulin ( CaM ) are decreased. Isolated fat cells of diabetic animals synthesized less CaM and contained reduced levels of CaM mRNA. Treatment of diabetic animals with insulin restores CaM transcripts to normal levels. Likewise, decreased steady-state levels of CaM mRNA in hepatocytes from diabetic animals are restored to normal levels with in vitro insulin incubation. Data from nuclear run-on assays demonstrate that insulin stimulates transcription of the CaM gene. In addition, insulin decreases the rate of CaM mRNA degradation. These data indicate that CaM mRNA levels are regulated by insulin's effects at the transcriptional and post-transcriptional level. It is postulated that in uncontrolled diabetes, elevations in tissue cAMP levels result, in part, from decreased activity of the apparently co-regulated PDE and CaM and that PDE inactivation results from both insulin insufficiency and CaM down-regulation.

Using a rat hepatoma H411E cell line, Dr. Solomon has examined CaM gene expression. Using antisense to the CaM I gene, he has been able to inhibit insulin stimulation of low km cAMP PDE, thereby tying activation of PDE to availability of CaM . Furthermore, the CaM I gene promoter, ligated to a luciferase reporter, was transfected into H-411E cells. From truncation - mutation experiments, Dr. Solomon's Lab has shown that the transcription factor Sp1 is critical for both basal and insulin stimulated transcription of CaM I gene. Insulin stimulated transcription of a CaM I-Luc fusion gene that extended from -207 to +185 indicating the presence of an insulin response element (IRE) here. Other experiments have identified the 2 upstream Sp1 sites as being more important than the 1 downstream site. The Lab has extended this work by demonstrating an inhibitory role for Sp4 and Sp3 compared to the stimulatory Sp1. Furthermore, using diabetic animals, Sp1 was markedly diminished in the liver of streptozotocin diabetic (STZ-DM) rats, and restored to normal after insulin treatment. Dr. Solomon's lab has also discovered that glucagon also stimulates Sp1, but whereas insulin stimulates transcription of CaM I gene expression, glucagon does not. Apparently, this difference is tied in part to the O-glycosylation status of the Sp1, which regulates its activity, degradability, etc. Additional work demonstrates the critical role of O-Glycosylation (O-GlcNAc) giving way to phosphorylation of critical Ser/Thr sites, to create a "shuttle" which can be demonstrated for insulin's action on the CaM gene. Future studies of this laboratory are designed to extend our knowledge of how insulin regulates CaM gene transcription, and facilities physiologic processes related to this, including the reversal of diabetic ketoacidosis.

Mechanisms Involved in TNF-a Induction of Insulin Resistance

Work from our laboratories has determined the site(s) of the TNF-a molecule inducing the insulin resistance in modeled systems (liver cells in culture). There are 2 peptides, TNF-a (69-100)) and TNF-a (133-157) , which regulate the resistance. (J. Lab Cln. Med. 130: 139-146, 1997). We have studied the effects of ceramide, downstream metabolite of the TNF-a . Additional work in the area has characterized the proteome for TNF-a -induced insulin resistance. Work is ongoing to identify the genes involved and how therapeutic intervention affects this.

NIH (NIDDKA: Short Term Medical Students Research Training Grant

This grant is in its 25 th year of operation under Dr. Solomon's direction.


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