Summarize the physiologic effects of insulin.
Insulin is produced by the pancreatic beta
islet cells as a prohormone, which is converted by proteolytic cleavage to
insulin and C peptide. Its metabolism takes place in the liver and kidney.
Normal insulin production approximates 40–50 U/day. Its half-life is measured
Insulin release is stimulated primarily by
glucose and amino acids. Its primary effect on carbohydrate homeo-stasis is to
inhibit hepatic glucose production and drive glucose into skeletal muscle.
Insulin does not affect the transport of glucose into brain or hepatic cells.
Insulin stimulates hepatic glucose storage as glycogen and inhibits lipolysis.
Because diabetics have depleted glycogen stores, proteins must be degraded to
make glucose. Insulin also assists the transport of amino acids into skeletal
muscle. Consequently, insulin deficiency predisposes to protein catabolism.
Insufficient insulin leads to fat breakdown, forming fatty acids and ketones.
Amounts of insulin suffi-cient to prevent lipolysis may not be enough to
prevent hyperglycemia. Therefore, severe hyperglycemia generally accompanies
A 24-hour fast is associated with a mild
insulin defi-ciency and a resultant decrease in peripheral glucose uptake.
Glycogen, protein, and triglyceride synthesis decrease, while the breakdown of
these storage molecules is accelerated. Counter-regulatory hormones play an
impor-tant role in the breakdown of macromolecules. Decreased circulating
insulin decreases glucose uptake in insulin-sensitive tissues to spare glucose
for obligate use by the central nervous system (CNS). Hepatic glucose
production is maintained for 12–24 hours by the breakdown of stored glycogen.
Subsequent hepatic glucose production depends on breakdown of peripheral
proteins and fat. In pro-longed fasts, ketone bodies are produced from the
break-down of adipose tissue to provide a substrate that can be metabolized by
Diabetic ketoacidosis (DKA) develops when
severe insulin deficiency is present. It is marked by hyperglycemia, which is a
result of increased hepatic glucose production and decreased peripheral uptake.
Ketone body production occurs in the hepatocyte mitochondria from oxidation of
fatty acids. In contrast to the euinsulinemic fed state, fatty acids freely
enter the mitochondria while fatty acid and triglyceride synthesis are
inhibited. The physiologic derangements of DKA (acidosis, ketonuria, osmotic
diure-sis, and hyperosmolarity) develop from the hyperglycemia and