Pancreatic endocrine function in cortisol-treated thyroidectomized calves.

1. Pancreatic endocrine function has been investigated in thyroidectomized calves given exogenous cortisol (2.0 mg.kg-1.day-1) in order to produce overt signs of diabetes. 2. Whenever this diabetic syndrome was induced it was associated with falling plasma insulin concentrations. A few days later, there was a significant rise in the post-absorptive concentration of both pancreatic glucagon and pancreatic polypeptide (PP) in the arterial plasma. Elevated levels of both hormones invariably persisted until the animals were given thyroxine. 3. Each of the pancreatic endocrine responses to cortisol was reversed by daily administration of thyroxine (25 microgram.kg-1. day-1) and the plasma glucose concentration was restored to normal within a few days. 4. Starvation was found to be an extremely effective way of reducing both the plasma glucose and glucagon concentration of diabetic calves without apparently affecting the concentration of either insulin of PP. 5. Neurally mediated release of insulin in response to 2-deoxyglucose, but not of either pancreatic glucagon or PP, was found to be defective in diabetic calves and recovered in response to thyroxine. 6. These results suggest that the primary defect that leads to the development of this diabetic syndrome in cortisol-treated thyroidectomized calves is failure of insulin release but that this is associated with consequential changes in the rates at which both glucagon and PP are released from the pancreas.