Pharmacodynamic properties
Insulin activates insulin receptors and therewith a complex cell signaling cascade which results in increased glucose uptake into the cells. The main effects of insulin are the reduction in circulating blood glucose concentrations and the storage of fat. Overall insulin influences the regulation of the carbohydrate and fat metabolism.
Under clinical field conditions in diabetic cats the maximal action on blood glucose concentrations (e.g. blood glucose nadir) after subcutaneous administration was observed at a mean of 6 hours (range 3 to 9 hours). In the majority of cats the glucose lowering effect lasted for a minimum of 9 hours after first insulin injection.
Pharmacokinetic particulars
Absorption: Protamine zinc recombinant human insulin is an insulin whose absorption and onset of action is delayed by the addition of protamine and zinc leading to crystal formation. After subcutaneous injection, proteolytic tissue enzymes degrade protamine to permit the absorption of insulin. In addition, interstitial fluid will dilute and break down the formed zinc insulin hexamer complexes and result in a delayed absorption from the subcutaneous depot.
Distribution: Once absorbed from the subcutaneous site, insulin will enter the circulation and diffuse into tissues, where it binds to insulin receptors found on most tissues. Target tissue organs are i.e. liver, muscle and adipose tissue.
Metabolism: Following the binding of insulin with the insulin receptor and the subsequent action, insulin is released back into the extracellular environment. It may then be degraded on passage through the liver or by the kidney. Degradation normally involves endocytosis of the insulin-receptor complex, followed by the action of insulin-degrading enzyme.
Elimination: The liver and the kidney are the two main organs which eliminate insulin from the circulation. Forty per cent of insulin is eliminated by the liver and 60% is eliminated by the kidney.