In the 1960's, Sodi-Pallares and colleagues of the National Institute of Cardiology in Mexico City advocated the use of infusions of glucose, insulin and potassium (GIK) in the management of patients with acute myocardial infarction. Insulin was thought to help cardiac function by increasing permeability to both glucose and potassium across the cell membranes and thus increasing electrical potential and functionality of myocardial fibers. Recent clinical evidence suggests a revival in the concept of GIK therapy. Researchers have found that GIK infusions to be beneficial in patients suffering from cardiogenic shock. Related findings are an association between the deficiency in the secretion of insulin and the incidence of heart failure, as well as an increase in cardiac performance in juvenile diabetic patients treated with this hormone.

It is now widely accepted that glucose is required as a good energy source for heart cells, and potassium is essential for their responsiveness. Moreover, insulin itself now appears to directly increase the force of contraction (positive inotropic effect) and the speed (chronotropic effect) of the cardiac muscle in various animal models. These effects can be found in the intact heart of the dog when pyruvate, fumarate and glutamate replace glucose as substrate suggesting that membrane systems involved in calcium transport in the rat heart cells are targets for this hormone.

To better define the direct inotropic effects of insulin at the cellular level and understand its mechanism of action, researchers at the Rees-Stealy Research Foundation are evaluating the effects of insulin on isolated single adult rat ventriculocytes, monitoring contractile status of the cells using an on line video edge detection system. The changes in contractile parameters affected in cardiomyocytes, and its relationship to postulated glucose uptake and calcium-activating mechanisms were reported in a paper presented in the 1996 meeting of the Federation of American Societies of Experimental Biology held on April 14, 1996 in Washington, D.C. by Béjar.

Insulin apparently activates the signaling pathway resulting in the movement of the molecules essential to allow glucose across the cell membrane. This may indicate that glucose metabolism is associated with the positive contraction effect. The chain of events that lead to this activation is the subject of study of Drs. Krown, Béjar, and Paolini. The scientists are particularly interested in the role played by a protein known as IRS-1 or insulin receptor substrate1 that is activated in response to insulin. A better definition of the role of IRS-1 is the goal of the study. This research is possible thanks to a generous grant from the California Metabolic Research Foundation.