GLUT 1 All tissues, especially red cells, brain 1–2 GLUT 2 Beta cells of pancreas; liver, kidney; gut 15–20 GLUT 3 Brain, placenta <1 GLUT 4 Muscle, adipose ~5 GLUT 5 Gut, kidney 1–2
FIGURE 41–4 Insulin promotes synthesis (from circulating nutrients) and storage of glycogen, triglycerides, and protein in its major target tissues: liver, fat, and muscle. The release of insulin from the pancreas is stimulated by increased blood glucose, incretins, vagal nerve stimulation, and other factors (see text).
Glucagon is extensively degraded in the liver and kidney as well as in plasma and at its tissue receptor sites. Its half-life in plasma is between 3 and 6 minutes, which is similar to that of insulin.
Pharmacologic Effects of Glucagon
A. Metabolic Effects
The first six amino acids at the amino terminal of the glucagon molecule bind to specific Gs protein–coupled receptors on liver cells. This leads to an increase in cAMP, which facilitates catabolism of stored glycogen and increases gluconeogenesis and ketogenesis. The immediate pharmacological result of glucagon infusion is to raise blood glucose at the expense of stored hepatic glycogen. There is no effect on skeletal muscle glycogen, presumably because of the lack of glucagon receptors on skeletal muscle. Pharmacological amounts of glucagon cause release of insulin from normal pancreatic beta cells, catecholamines from pheochromocytoma, and calcitonin from medullary carcinoma cells.
Basal uptake of glucose; transport across the blood-brain barrier Regulation of insulin release, other aspects of glucose homeostasis Uptake into neurons, other tissues Insulin-mediated uptake of glucose Absorption of fructose
TABLE 41–3 Endocrine effects of insulin.
Effect on liver:
Reversal of catabolic features of insulin deficiency
Inhibits conversion of fatty acids and amino acids to keto acids
Inhibits conversion of amino acids to glucose
Promotes glucose storage as glycogen (induces glucokinase and glycogen synthase, inhibits phosphorylase)
Effect on muscle:
Effect on adipose tissue:
Lipoprotein lipase is induced and activated by insulin to hydrolyze triglycerides from lipoproteins
Glucose transport into cell provides glycerol phosphate to permit esterification of fatty acids supplied by lipoprotein transport
Intracellular lipase is inhibited by insulin
B. Cardiac Effects
Glucagon has a potent inotropic and chronotropic effect on the heart, mediated by the cAMP mechanism described above. Thus, it produces an effect very similar to that of β-adrenoceptor agonists without requiring functioning β receptors.
C. Effects on Smooth Muscle
Large doses of glucagon produce profound relaxation of the intestine. In contrast to the above effects of the peptide, this action on the intestine may be due to mechanisms other than adenylyl cyclase activation.
A. Severe Hypoglycemia
The major clinical use of glucagon is for emergency treatment of severe hypoglycemic reactions in patients with type 1 diabetes when unconsciousness precludes oral feedings and intravenous glucose treatment is not possible. Recombinant glucagon is currently available in 1-mg vials for parenteral (IV, IM, or SC) use (Glucagon Emergency Kit).
B. Endocrine Diagnosis