Insulin Actions

  • The net effect of insulin secretion is a reduction in blood glucose concentration, promotion of nutrient storage, and prevention of post-prandial spikes in blood potassium. Insulin achieves these effects by means of activating a specific receptor on a wide variety of tissues and in doing so modulating target tissue physiology.
Molecular Action
  • Insulin-responsive cells express Insulin Receptor on their membranes which specifically bind circulating Insulin. The mature Insulin Receptor is composed two extracellular alpha subunits each of which is conjugated to a membrane-spanning beta subunit by disulfide bonds. Alpha subunits cooperate to bind circulating insulin while beta subunits possess tyrosine kinase enzymatic activity which is silent in the absence of insulin. Upon binding of Insulin to the alpha subunits, the tyrosine kinase activity of the beta subunits of Insulin Receptor is stimulated and targets a wide variety of proteins for phosphorylation. Phosphorylation of these secondary proteins can radically change the behavior of cell and thus the entire insulin-responsive tissue.
Physiological Actions
  • Overview
    • Most of the cells in the body are responsive to insulin but its most important effects are mediated by the major metabolic organs of the body which include the liver, adipose tissue, and muscle. In general, the presence of insulin induces these organs to coordinate storage of available nutrients and absorb potassium. Consequently, insulin is probably the major anabolic hormone in the body.
  • Liver
    • Insulin acts on hepatocytes to inhibit gluconeogenesis and activate glycogenesis, resulting in glycogen storage within the liver. Once glycogen stores become maximal, the continued presence of insulin promotes fatty acid synthesis resulting in any excess glucose being converted into fatty acids. These fatty acids are then used to synthesize triglycerides which are exported in apolipoprotein complexes into the circulation for uptake by adipocytes.
  • Adipose Tissue
    • Insulin modulates multiple enzymatic activities in adipocytes to promote fat storage. First, insulin reduces intracellular lipase levels, thus reducing lipid metabolism within adipocytes. In contrast, insulin increases extracellular lipase levels which cleave circulating lipoprotein-associated triglycerides, previously synthesized by the liver, into fatty acids which are then imported into adipocytes. Finally, insulin enhances adipocyte uptake of glucose which is metabolized into glycerol and then combined with imported fatty acids to generate triglycerides. In this way, insulin coordinates synthesis of triglycerides within adipocytes which ultimately results in overall fat storage.
  • Muscle
    • The post-prandial spike in insulin acts on myocytes to increases glucose import and shifts muscle metabolism to primarily use glucose as an energy source; furthermore, any excess glucose imported is stored as glycogen in the presence of insulin. Insulin promotes amino acid import and protein synthesis in muscle and nearly all the body's cells; in contrast, insulin inhibits protein degradation and metabolism.
  • Potassium Balance
    • As discussed in internal potassium balance insulin promotes K+ uptake into a variety of the body's cells thus preventing potentially dangerous spikes in extracellular potassium concentration following a meal.