During normal daily living, the maintenance of normal blood glucose concentrations depends on the balance between two peptide hormones, insulin and glucagons, which are made in distinct pancreatic islet cells and elicit different cellular responses. Insulin, which lowers blood glucose, contains two polypeptide chains linked by disulfide bonds and is synthesized by the β cells in the islets (see Figures 14-23 and 14-24). Glucagon, a monomeric peptide, is produced by the α islet cells and raises blood glucose. The availability of blood glucose is regulated during periods of abundance (following a meal) or scarcity (following fasting) by the adjustment of insulin and glucagon concentrations in the blood.
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Our focus here will be on the key hormone insulin, which acts in several ways to reduce the level of blood glucose:
Within seconds, insulin induces an increase in the uptake of glucose from the blood into muscle and fat cells, primarily by increasing the number of GLUT4 glucose transporters on the plasma membrane (see Figure 16-40 below).
Within seconds to minutes, insulin stimulates glycogen synthesis from glucose in the liver.
Over a longer time frame, insulin acts on the liver to inhibit synthesis of enzymes that catalyze the synthesis of glucose from smaller metabolites, a process termed gluconeogenesis.
Insulin enhances the formation of adipocytes from progenitor cells, increasing the body’s storage of fatty acids as triglycerides.
Insulin acts on the nearby α cells in the pancreatic islets to inhibit glucagon synthesis.
A lowering of blood glucose stimulates glucagon release from pancreatic α cells. Like the epinephrine receptor, the glucagon receptor, found primarily on liver cells, is coupled to the Gαs protein, whose effector protein is adenylyl cyclase. The binding of glucagon to this receptor induces a rise in cAMP, leading to activation of protein kinase A, which inhibits glycogen synthesis and promotes glycogenolysis, yielding glucose 1-