Porcine insulin zinc suspension in the management of feline diabetes mellitus (Sponsored by Intervet Schering-Plough Animal Health)

Porcine insulin zinc suspension in the management of feline diabetes mellitus (Sponsored by Intervet Schering-Plough Animal Health)

Vetsulin (porcine insulin zinc suspension) is approved by the FDA for reducing hyperglycemia and hyperglycemia-associated clinical signs in cats with diabetes mellitus. Internationally, it was first approved for use in the early 1990s and is registered for dogs and cats as Caninsulin in more than 30 other countries.

Vetsulin is supplied as a sterile injectable suspension in multidose vials of either 2.5 ml or 10 ml of 40 U/ml (U-40) porcine insulin zinc suspension. Vials are supplied in cartons of one 10-ml vial and cartons containing ten 2.5-ml vials. Vetsulin should be administered using a U-40 insulin syringe. Use of a syringe other than a U-40 will result in incorrect dosing. Vetsulin should be kept refrigerated. It is good clinical practice to replace opened vials on a monthly basis.

Species differences in insulin

Table 1. Amino acid comparison of insulin between selected species
Pork insulin is a protein composed of 51 amino acids, arranged in two chains (an acidic A chain and a basic B chain) cross-linked by disulphide bridges.1 The amino acid sequence of insulin is highly conserved among vertebrates, with little variation in the amino acid sequence of the 21 amino acid A chain and the 30 amino acid B chain. Pork insulin has the same A-chain structure as canine and human insulin but differs slightly from feline insulin, as shown in Table 1. Pork insulin has the same B-chain structure as canine, feline, and bovine insulin but differs slightly from human insulin, as shown in Table 1.

Insulin from one mammal is biologically active in another. All mammalian insulins, irrespective of species origin, bind with a similar affinity to insulin receptors at the three sites of action—muscle, adipocyte, and hepatocyte—and initiate post receptor events in terms of autophosphorylation.2 Pork insulin is used effectively and safely in long-term human, canine, and feline cases.

Differences in amino acid structure of insulin from different species result in slightly different solubility, which in turn affects activity. For example, pork and beef zinc insulin crystals are more fat soluble than human zinc insulin crystals and, therefore, cross the blood-brain barrier more readily than human insulin. In practice, although patients on animal derived insulins may theoretically be aware of the onset of hypoglycemic episodes earlier, this difference is not completely clear.

Insulin pharmacokinetics and pharmacodynamics

The healthy pancreas secretes endogenous insulin as monomers (single molecules) from the beta cells of the islets of Langerhans. In contrast, exogenous insulin, for subcutaneous injection, consists of complex hexamers (complexes containing six subunits) that are broken down into monomers and dimers (molecules with two similar subunits) after subcutaneous administration. Monomers and dimers can be absorbed into the bloodstream more easily than hexamers. Different insulin products liberate monomers and dimers at different rates; however, once exogenous insulin has been absorbed from the subcutaneous injection site, the origin of the insulin has no effect on its ability to function in the body. Thus, it is the insulin formulation that determines the rate and extent of absorption, and the glycemic effects in the body. The rate at which the insulin is absorbed determines its duration of action. Rapid-acting insulins are absorbed quickly; however, they also have a short duration of action. In general, shorter-acting insulins (both rapid-acting and intermediate type insulins) are more consistently and completely absorbed, which gives more predictable glycemic effects, than long-acting insulins.

Vetsulin contains a combination of 30% amorphous and 70% crystalline zinc insulin, has a rapid onset of action, and has an intermediate duration of action following subcutaneous administration to cats. After subcutaneous injection, the amorphous component of Vetsulin releases monomers rapidly leading to a rapid onset of effect, whereas the crystalline component provides the intermediate duration of action due to a slower release of monomers.

In the bloodstream, insulin concentrations peak about two hours after Vetsulin is administered to cats with naturally occurring diabetes mellitus.3 Plasma insulin concentrations remain elevated for about nine to 12 hours. Vetsulin has an onset of action of less than two hours in diabetic cats with peak effects (blood glucose nadir) between 1.5 and eight hours after subcutaneous injection, although this varies between individuals.3-5 Based on blood glucose concentrations in diabetic cats, Vetsulin's duration of action is typically between eight and 12 hours.3,5,6