Signals for insulin secretion

Glucose is an effective stimulus for the release of insulin from pancreatic beta-cells but its pre-eminence for the physiological control of insulin secretion is now challenged. The insulin response to oral glucose is much greater than the response to intravenous glucose because an intestinal factor, or factors, has a powerful stimulant effect on insulin secretion. Conversely, the hyperglycaemia which accompanies sympathetic overactivity is accompanied by reduced plasma insulin levels because adrenaline inhibits pancreatic insulin by an alpha-adrenergic mechanism. Other hormonal and chemical factors also modify pancreatic insulin release. Plasma insulin levels will be determined not only by the interplay of signals which stimulate or inhibit insulin release but also by the rate at which insulin leaves the circulation. Because insulin is secreted into the portal circulation the concentration of insulin to which hepatocytes are exposed is normally greater than that affecting peripheral tissues. This ratio will be affected by portal venous diversion and might be altered by hepatic damage. Both factors might also influence the intestinal control of insulin secretion, as the gut 'hormone' would not have to traverse the liver, which might remove some of it, before it arrived at the pancreatic islets. If insulin is the key 'hepatotrophic factor' stimulating hepatic growth and regeneration, as well as preventing atrophy, we might expect it to induce hepatic growth in otherwise normal liver and we would expect it to be secreted in larger amounts when regeneration is active.