The purinergic nerve hypothesis and insulin secretion.

In adrenalectomized rats the effect of i.v. injection of glucose and ATP on insulin changes in external jugular vein was determined in normal and alloxan diabetic animals. In another set of experiments the direct effect of ATP on insulin secretion was investigated. Glucose and ATP were injected in the carotid artery and the blood samples were withdrawn from the portal vein. In these experiments there was immediate and excessive production of insulin release in the portal vein after ATP injection in the carotid artery. In alloxan diabetic rats, despite the high blood glucose levels, the plasma insulin was low and did not respond to glucose stimulation. ATP could increase the sensitivity of the diabetic rats to glucose. The possible role of purinergic nerves in insulin secretion is discussed. It is concluded that multiple innervation of the islets by purinergic, cholinergic and adrenergic nerves, regulate insulin secretion. It is suggested that: 1. Purinergic nerve stimulation is more specific for insulin secretion. 2. ATP is considered the principal transmitter released from purinergic nerves causing insulin secretion. 3. The insulin stimulatory effect normally produced by glucose is through purinergic nerves. 4. It could be possible that one of the causes of diabetes is a defect in the purinergic innervation of the islet cells thus the sensitivity of the islets to glucose is decreased.