Glycogen-storage disease in rats, a genetically determined deficiency of liver phosphorylase kinase

Abstract

Rats from an inbred strain (NZR/Mh) were found to have high concentrations of glycogen in their livers, even after 24 h of starvation. Despite this, blood glucose concentrations were well maintained on starvation for up to 72 h. The primary defect is a deficiency of liver phosphorylase kinase, causing a lack of active glycogen phosphorylase, although total phosphorylase is normal. The intravenous injection of glucagon caused a rapid activation of cyclic AMP-dependent protein kinase in the liver, but no increase in either phosphorylase kinase or phosphorylase a activity. Although total glycogen synthase activity in the livers of affected rats was higher than normal, glycogen synthase in the active form was very low, presumably as a result of the high liver glycogen content. The condition is transmitted as autosomal recessive and, apart from hepatomegaly, the affected rats appear healthy.

Mechanism of placental glycogen deposition in diabetes in the rat

“…It is possible that the hyperglycaemia-related accumulation of glycogen may have a stabilizing action on these enzymes, which are normally attached to the glycogen particles in the cell [34]. This possibility is supported by recent observations on liver phosphorylase kinase-deficient rats (gsd/gsd), in which glycogen storage is accompanied by increased levels of glycogen synthase [35]. The involvement of insulin has also to be considered, as glycogenesis is insulin-dependent in liver, muscle and adipose tissue.…”

Glucose homeostasis during the perinatal period in normal rats and rats with a glycogen storage disorder.

“…Despite their inability to mobilize liver glycogen the rats are able to maintain their blood glucose at a concentration that is only slightly lower than that found in normal animals in the fed state, and that does not fall significantly even after 72 h starvation (5). In all other respects they appear healthy with a normal life span and no evidence of increased fetal or neonatal mortality.…”

“…Glycogen was measured after digestion of the tissue and precipitation of the glycogen with ice-cold ethanol (7). The glycogen was then digested by aamyloglucosidase and measured as glucose equivalents (5).…”

“…Glycogen concentrations in most other tissues are comparable with those of normal rats except for small differences in lung and kidney. The condition is caused by a deficiency ofphosphorylase kinase activity and has been shown to be an autosomal recessive trait (5).…”

Glycerolphosphate acyltransferase, dihydroxyacetonephosphate acyltransferase and carnitine palmitoyltransferase in a glycogen storage disease (gsd/gsd) rat

“…The defect in these animals appears to result from a deficiency of liver phosphorylase kinase [2]. Besides exhibiting mild hypoglycaemia in the fed state and inability to mobilise glycogen in the fasted state, these animals show abnormalities in lipid metabolism in that they have diminished rates of hepatic fatty acid and cholesterol synthesis and considerably lower concentrations of plasma triacylglycerols [3].…”