Glucagon responses in rabbits with obstructive jaundice and a low energy status in the liver

Abstract

Glucagon has a choleretic effect and also stimulates energy-consuming reactions, such as gluconeogenesis and ureogenesis in the liver. The effect of glucagon on energy metabolism in the liver was analyzed in rabbits with obstructive jaundice that had severe liver damage, indicated by significantly lower hepatic energy charge levels. The gluconeogenetic responses to glucagon administration, as shown by increases in the plasma glucose levels, were usually observed in normal rabbits, but these responses were completely depressed after glucagon administration in rabbits with obstructive jaundice. The energy charge levels in the latter animals decreased even further after glucagon administration. Even though the energy consumption for gluconeogenesis after glucagon administration was limited in the jaundiced rabbits, it was sufficient to cause a deterioration in the hepatic energy balance. The above findings show that the administration of glucagon increases the amount of energy expended in the liver following a reduction in the hepatic energy charge in rabbits with obstructive jaundice. Therefore, even though glucagon has a choleretic effect, it should be administered carefully to patients with obstructive jaundice, especially in those with severe liver damage, such as in patients with cholangitis.

Lack of effect of incretin hormones on insulin release from pancreatic islets in the bile duct-ligated rats

“…Such was not the case for GLP-1 and GIP, although some stimulation may be required, as suggested for elevated levels of fat-induced GIP in cholestatic human subjects (24). It has been reported that glucagon injection into cholestatic animals resulted in abnormal responses (9). Because the incretin receptors are known to cause downregulation in pancreatic ␤-cells and other types of cells (7,16,22,23), it is possible that impairment of insulin release under cholestasis is, at least in part, due to desensitization of these receptors.…”

“…Obstructive jaundice has been reported to cause changes in plasma concentrations of incretins; plasma glucagon levels are increased in both patients and animals with bile duct obstruction (9,12). Indeed, circulating glucagon levels were raised in the BDL rats in the present study.…”