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 in minutes.
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 ketosis.
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 the CNS.
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 hyperketonemia.