When mixed with
insulin, protamines slow down the onset and increase the duration of insulin action (see
NPH insulin). Protamine is used in cardiac surgery, vascular surgery, and interventional radiology procedures to neutralize the anti-clotting effects of
heparin. Adverse effects include increased pulmonary artery pressure and decrease peripheral blood pressure, myocardial oxygen consumption, cardiac output, and heart rate.
Protamine sulfate is an antidote for
heparin overdose, but severe allergy may occur. A chain shortened version of protamine also acts as a potent heparin antagonist, but with markedly reduced
antigenicity. It was initially produced as a mixture made by
thermolysin digestion of protamine, but the actual effective peptide portion VSRRRRRRGGRRRR has since been isolated. An analogue of this peptide has also been produced. In gene therapy,
protamine sulfate's ability to condense plasmid DNA along with its approval by the U.S.
Food and Drug Administration (FDA) have made it an appealing candidate to increase transduction rates by both viral and nonviral (e.g. utilizing cationic liposomes) mediated delivery mechanisms. Protamine may be used as a drug to prevent obesity. Protamine has been shown to deter increases in body weight and
low-density lipoprotein in high-fat diet rats. This effect occurs through the inhibition of
lipase activity, an enzyme responsible for
triacylglycerol digestion and absorption, resulting in a decrease in the absorption of dietary fat. No liver damage was found when the rats were treated with protamine. However, emulsification of long-chain fatty acids for digestion and absorption in the small intestine is less constant in humans than rats, which will vary the effectiveness of protamine as a drug. Furthermore, human peptidases may degrade protamine at different rates, thus further tests are required to determine protamine's ability to prevent obesity in humans. == Species distribution and isoforms ==