Signal Transduction in Cardiovascular System Health and Disease highlights the major contributions of different signaling systems in modulating normal cardiovascular functions and how a perturbation in these signaling events leads to abnormal cell functions and cardiovascular disorders. This title is volume 3 in the new Springer series, Advances in Biochemistry in Health and Disease.

In 1996 the 75th anniversary of the discovery of insulin was celebrated at the University of Toronto, the scene of that discovery in 1921. This volume was stimulated by the scientific program which was staged at that time and brought together much of the world's best talent to discuss and analyze the most recent developments in our understanding of pancreatic function, insulin secretion, the interaction of insulin with its target tissues, the mechanism of insulin action at the cellular level, and the defects which underlie both Type I (insulin-dependent diabetes mellitus, IDDM) and Type II (noninsulin-dependent diabetes mellitus, NIDDM) forms of the disease. We have chosen to focus the present volume on work related to insulin action.

In vitro and animal studies show that vanadate and other Because most cellular components contain hydroxyl and/or vanadium compounds increase glucose transport activity and phosphate groups, vanadate reacts as shown in eq. 1, and 2 normalize glucose metabolism [1-5]. Furthermore, these with a variety of metabolites. For example, the reaction of insulin-mimetic compounds can be administered orally. Vana- vanadate with the 2'-hydroxyl group of the cofactor NAD date enhances the phosphoprotein formation which is attrib- generates an NADP analog, NADV (path b) [22]. NADV is uted to either the activation of protein kinases or inhibition an excellent cofactor for enzymes such as glucose-6-phos- of protein phosphatases. Despite the interest in document- phate dehydrogenase, 6-phosphogluconate dehydrogenase, ing the effects of vanadate on protein kinases, most reports and alcohol dehydrogenase [22]. The presence ofNADV have used indirect methods and studies with purified kinases could affect the levels of reducing equivalents in the cell, im- show weak, if any, interaction of vanadate with kinases as portant in maintaining a normal glucose metabolism. This a group of enzymes (reviewed in Refs. [6-8]). Vanadate type of mechanism is distinct from the vanadate-induced interacts potently with phosphatases and the inhibition is NADH oxidation by plasma membranes [23]. Organic attributed to a five-coordinate vanadate complex which vanadates have been shown to substitute for organic phos- mimics the transition state of the phosphate ester hydroly- phates in many of the enzymes related to glucose metabolism sis reaction (reviewed in Refs. [7,9]).