• Insulin, naturally secreted by the pancreas, enters the portal vein and passes straight to the liver, where half of it is taken up. The rest enters and is distributed in the systemic circulation so that its concentration (in fasting subjects) is only about 15% of that entering the liver.

• When insulin is injected s.c. it enters the systemic circulation and both liver and other peripheral organs receive the same concentration.

This difference may have clinical importance and this is why some continous infusion pumps (see below) deliver insulin intraperitoneally rather than subcutaneously.

In conventional use, insulin is injected (s.c., i.m. or i.v.) as it is digested if swallowed. It is absorbed into the blood3 and is inactivated in the liver and kidney; about 10% appears in the urine. The t1/, is 5 min.

In addition to needles and syringes, alternative techniques for insulin administration have been developed, some availing themselves of the kinetics of insulin: insulin pens (supplied preloaded or with replaceable cartridges), external infusions and implantable pumps. These latter are convenient for an accurately controlled continuously functioning biofeedback system, but pose difficulties for routine replacement in insulin deficiency. Therefore sustained-release (depot) formulations are used to provide an approach reasonably near to natural function and compatible with the convenience of daily living. An even closer approach is provided by the development of (at present inevitably expensive) miniaturised infusion pumps which can be used by reliable patients.

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