Glucagon-Induced Hyperglycemia as an Index of Liver Function 12

Abstract

Glucagon is a protein substance in pancreatic extracts which raises blood glucose by stimulating hepatic glycogenolysis (1-3). For this reason, it has been termed the hyperglycemic glycogenolytic factor (HGF) of the pancreas. Sutherland and Cori (2) have shown that glucagon increases the concentration of active phosphorylase in liver slice preparations. Apparently, glucagon administration does not induce glycogenolysis in muscle (4, 5).Whether glucagon has an effect on extrahepatic utilization of glucose is still a matter of controversy. Drury, Wick, and Sherrill (6) have reported that the rate of uptake of C'4-labeled glucose by eviscerated-nephrectomized rabbits actually decreases when glucagon is administered to such animals. On the other hand, Root, Ellis, and Staub (7), using intact rabbits and mice, have demonstrated that the presence of glucagon in insulin solutions in ratios of from 1: 100 to 1: 1 does not influence the degree of hypoglycemia produced by insulin and does not alter the potency of the insulin preparation as determined by the mouse convulsion assay. Ingle, Nezamis, and Humphrey (8) were unable to demonstrate any influence of glucagon upon extrahepatic glucose utilization in eviscerated rats. Using peripheral arteriovenous glucose differences as an index of peripheral glucose utilization in healthy human subjects, Van Itallie, Morgan, and Dotti (9) have found that glucagon does not inhibit and may accelerate uptake of glucose by peripheral tissues.It has been known for many years that the diseased liver usually does not contain a normal quantity of glycogen.

Effects of Epinephrine on Forearm Blood Flow and Metabolism in Man *

“…Several reports deal with changes in a-v or capillary-venous glucose differences after subcutaneous administration of epinephrine to man (32)(33)(34)(35). These studies ought not to be invoked as evidence, since they ignored the changes in blood flow produced by epinephrine and they ignored the errors introduced by a changing arterial concentration, which must be considered if metabolism is to be measured (7).…”

The Blood Sugar and Serum Insulin Response to Intravenous Glucagon in Chronic Renal Failure

“…The degree of hyperglycemia following glucagon administration is related to the hepatic content of glycogen (4). In addition, glucagon directly stimulates the secretion of insulin from the beta cells ( 5 , 6 ) .…”

Plasma cyclic AMP levels during a secretin-caerulein pancreatic function test in liver and pancreatic disease.

“…Thus, the high levels of cyclic AMP observed in liver disease during secretin infusion cannot be explained by increased sensitivity of the liver plasma membrane to the hormone. That glucagon-induced hyperglycaemia is altered in patients with liver disease has already been reported by Van Itallie and Bentley (1955).…”