When glucose enters the bloodstream from the intestine after a carbohydrate-rich meal, the resulting increase in blood glucose causes increased secretion of insulin (and decreased secretion of glucagon). Insulin release by the pancreas is largely regulated by the level of glucose in the blood supplied to the pancreas. The peptide hormones insulin, glucagon, and somatostatin are produced by clusters of specialized pancreatic cells, the islets of Langerhans (Fig. 23-24). Each cell type of the islets produces a single hormone: a cells produce glucagon; 3 cells, insulin; and 8 cells, somatostatin.
When blood glucose rises, GLUT2 transporters carry glucose into the 3 cells, where it is immediately converted to glucose 6-phosphate by hexokinase IV (gluco-kinase) and enters glycolysis (Fig. 23-25). The increased rate of glucose catabolism raises [ATP], causing the closing of ATP-gated K+ channels in the plasma membrane. Reduced efflux of K+ depolarizes the membrane, thereby opening voltage-sensitive Ca2+ channels in the plasma membrane. The resulting influx of Ca2 +
triggers the release of insulin by exocytosis. Stimuli from the parasympathetic and sympathetic nervous systems also stimulate and inhibit insulin release, respectively. A simple feedback loop limits hormone release: insulin lowers blood glucose by stimulating glucose uptake by the tissues; the reduced blood glucose is detected by the 3 cell as a diminished flux through the hexokinase reaction; this slows or stops the release of insulin. This feedback regulation holds blood glucose concentration nearly constant despite large fluctuations in dietary intake.
FIGURE 23-24 The endocrine system of the pancreas. In addition to the exocrine cells (see Fig. 18—3b), which secrete digestive enzymes in the form of zymogens, the pancreas contains endocrine tissue, the islets of Langerhans. The islets contain a, 3, and 8 cells (also known as A, B, and D cells, respectively), each cell type secreting a specific polypeptide hormone.
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