A blood glucose level above the normal 70 mg/100 mL (70 mg/dL) stimulates release of insulin from beta cells, leading to uptake and storage of glucose by liver and muscle. The resultant decrease in the blood glucose level stops in sulin secretion. Some amino acids also stimulate insulin secretion, either alone or in concert with elevated blood glucose levels. Increased blood fatty acid levels also stimulate insulin release, as do circulating gastrin, CCK, and secretin. CCK and glucagon, released in the islet by the A cells, act as paracrine secretions to stimulate B cell secretion of insulin.
Blood glucose levels below 70 mg/100 mL stimulate release of glucagon; blood glucose levels significantly above 70 mg/100 mL inhibit glucagon secretion. Glucagon is also released in response to low levels of fatty acids in the blood. Insulin inhibits release of glucagon by A cells, but because of the cascading circulation in the islet (see below), this inhibition is effected by a hormonal action of insulin carried in the general circulation.
The islets have both sympathetic and parasympathetic innervation. About 10% of the islet cells have nerve endings directly on their plasma membrane. Well-developed gap junctions are located between islet cells. Ionic events triggered by synaptic transmitters at the nerve endings are carried from cell to cell across these junctions. Autonomic nerves may have direct effects on hormone secretion by A and B cells.
Parasympathetic (cholinergic) stimulation increases secretion of both insulin and glucagon; sympathetic (adrenergic) stimulation increases glucagon release but inhibits insulin release. This neural control of insulin and glucagon may contribute to the availability of circulating glucose in stress reactions.
The blood supply to the pancreas provides a cascading perfusion of the islets and acini
Several arterioles enter the periphery of the islets and branch into fenestrated capillaries. In humans, the capillaries first perfuse the A and D cells, peripherally, before the blood reaches the B cells, centrally. Larger vessels that travel in septa that penetrate the central portion of the islet are also accompanied by A and D cells, so that blood reaching the B cells has always first perfused the A and D cells.
Large efferent capillaries leave the islet and branch into the capillary networks that surround the acini of the exocrine pancreas. This cascading flow resembles the portal systems of other endocrine glands (pituitary, adrenal).
Secretions of the islet cells have regulatory effects on the acinar cells:
• Insulin, the vasoactive intestinal peptide (VIP), and CCK stimulate exocrine secretion.
• Glucagon, pancreatic polypeptide (PP), and somatostatin inhibit exocrine secretion.
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