At least four polypeptides with regulatory activity are secreted by the islets of Langerhans in the pancreas. Two of these are hormones insulin and glucagon and have important functions in the regulation of the intermediary metabolism of carbohydrates, proteins, and fats. The third polypeptide, somatostatin, plays a role in the regulation of islet cell secretion, and the fourth, pancreatic polypeptide, is probably concerned primarily with the regulation of HCO– 3 secretion to the intestine. Glucagon, somatostatin, and possibly pancreatic polypeptide are also secreted by cells in the mucosa of the gastrointestinal tract.
Islet cell structure
The islets are scattered throughout the pancreas, although they are more plentiful in the tail than in the body and head. β-islets make up about 2% of the volume of the gland, whereas the exocrine portion of the pancreas (see Chapter 26) makes up 80%, and ducts and blood vessels make up the remainder. Humans have 1 to 2 million islets. Each has a copious blood supply; blood from the islets, like that from the gastrointestinal tract (but unlike that from any other endocrine organs), drains into the hepatic portal vein.
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Structure, biosynthesis, & secretion of insulin
Insulin is a polypeptide containing two chains of amino acids linked by disulfide bridges. Minor differences occur in the amino acid composition of the molecule from species to species.
Biosynthesis & secretion
Insulin is synthesized in the rough endoplasmic reticulum of the B cells. It is then transported to the Golgi apparatus, where it is packaged into membrane-bound granules. These granules move to the plasma membrane by a process involving microtubules, and their contents are expelled by exocytosis. The insulin then crosses the basal lamina of the B cell and a neighboring capillary and the fenestrated endothelium of the capillary to reach the bloodstream.
Effects of insulin
The physiologic effects of insulin are far-reaching and complex. They are conveniently divided into rapid, intermediate, and delayed actions, as listed. The best known is the hypoglycemic effect, but there are additional effects on amino acid and electrolyte transport, many enzymes, and growth. The net effect of the hormone is the storage of carbohydrates, protein, and fat. Therefore, insulin is appropriately called the “hormone of abundance.”
The fate of secreted insulin & insulin-like activity in blood
Plasma contains a number of substances with insulin-like activity in addition to insulin. The activity that is not suppressed by anti-insulin antibodies has been called nonsuppressible insulin-like activity (NSILA). Most, if not all, of this activity, persists after pancreatectomy and is due to the insulin-like growth factors IGF-I and IGF-II. These IGFs are polypeptides. Small amounts are free in the plasma (low-molecular-weight fraction), but large amounts are bound to proteins (high-molecular-weight fraction). One may well ask why pancreatectomy causes diabetes mellitus when NSILA persists in the plasma. However, the insulin-like activities of IGF-I and IGF-II are weak compared to that of insulin and likely play other specific functions.
Insulin increases the entry of glucose into cells. In skeletal muscle cell, it increases the number of GLUT 4 transporters in the cell membranes. In the liver it induces glucokinase, which increases the phosphorylation of glucose, facilitating the entry of glucose into the cell.
Insulin causes K+ to enter cells, with a resultant lowering of the extracellular K+ concentration. Insulin increases the activity of Na+–K+ ATPase in cell membranes so that more K+ is pumped into cells. Hypokalemia often develops when patients with diabetic acidosis are treated with insulin.