Der Insulinspiegel im Blut steigt nach einer Mahlzeit an und kehrt nach 1 bis 2 Stunden auf den Basalwert zurück. Aber auch der basale Insulinspiegel ist nicht konstant. Er oszilliert mit einer regelmäßigen Periode von 3 bis 6 Minuten. Nach einer Mahlzeit steigt zwar die Amplitude an, aber die Periode bleibt gleich.[1]
Es wird angenommen, dass diese Oszillationen wichtig für den Erhalt der Insulinsensitivität ist. Es wird dadurch die Down-Regulation der Insulinrezeptoren in den Zielgeweben verhindert.[1]
Such down regulation underlies insulin resistance, which is common in type 2 diabetes. It would therefore be advantageous to administer insulin to diabetic patients in a manner mimicking the natural oscillations. [1] The insulin oscillations are generated by pulsatile release of the hormone from the pancreas. Insulin originates from beta cells located in the islets of Langerhans. Since each islet contains up to 2000 beta cells and there are one million islets in the pancreas it is apparent that pulsatile secretion requires sophisticated synchronization both within and among the islet of Langerhans.
Mechanism
BearbeitenPulsatile insulin secretion from individual beta cells is driven by oscillation of the calcium concentration in the cells. In beta cells lacking contact the periodicity of these oscillations is rather variable (2-10 min). However, within an islet of Langerhans the oscillations become synchronized by electrical coupling between closely located beta cells that are connected by gap junctions, and the periodicity is more uniform (3-6 min). [1]
Pulsatile insulin release from the entire pancreas requires that secretion is synchronized between 1 million islets within a 25 cm long organ. This synchronization is accomplished by intrapancreatic neurons and does not require neural input from the brain. It is not entirely clear which neural factors account for this synchronization but ATP as well as the gasses NO and CO may be involved. [1] The effect of these neural factors is to induce sudden dramatic elevation of calcium in the cytoplasm by releasing calcium from the endoplasmic reticulum (ER) of the beta cells. This elevation results in release of ATP from the beta cells. The released ATP in turn binds to receptors on neighbouring beta cells leading to a regenerative wave of rapid calcium elevation among the cells within the islet. This signal is believed to entrain pulsatile insulin release from the islets into a common pancreatic rhythm. [1]
Clinical significance
BearbeitenThe insulin oscillations are particularly pronounced in the portal vein delivering blood from the pancreas to the liver, which is a major insulin target. Disturbances of the insulin oscillations occur early in diabetes and may contribute to insulin resistance. Pulsatile insulin delivery to the portal vein or islet cell transplantation to the liver of diabetic patients are therefore attractive therapeutic alternatives. [1]