Rat Strain Differences in Gluconeogenesis by Isolated Hepatocytes

Abstract

An investigation of the glucose production by isolated hepatocytes from lipemic BHE and nonlipemic Wistar rats was conducted. Hepatocytes were isolated from 40-hr starved young rats. Glucose, P-hydroxybutyrate, and acetoacetate production and ATP content of the cells after 60 min incubation with a variety of substrates were determined. BHE hepatocytes produced more glucose and /3-hydroxybutyrate than Wistar hepatocytes. No strain differences in ATP content were observed. It is suggested that, in part, the hyperglycemia observed in the mature BHE rat may have its origins in the increased hepatic gluconeogenic capacity of this strain.Charles River, Wilmington, Mass. 74

The Cdb:BHE Rat--A Model for Non-Insulin-Dependent, Nonobese Diabetes Mellitus

“…This observation was expected; however, they also reported an increase in fatty acid oxidation. The latter observation is consistent with our finding of a tenfold elevation in serum free glycerol, a product of peripheral tissue lipolysis, and an increase in hepatic glycerol use for glucose synthesis and fatty acid reesterification (Berdanier et al, 1978(Berdanier et al, , 1982. Detailed studies of frozen-clamped hepatic tissue from stock-dietfed rats, (a process in which large clamps, immersed in liquid nitrogen, smash the excised liver to the thinness of a potato chip) revealed that liver cells had elevated phosphorylation and redox states, findings consistent with elevated rates of hepatic lipogenesis (Berdanier et al, 1979).…”

“…As mentioned previously, gluconeogenesis by isolated hepatocytes from rats starved for 40 hours is 20 percent greater in BHE rats than in WI or SD rats fed a stock diet ad libitum (Berdanier, 1982). Gluconeogenesis can be increased by feeding a 65 percent sucrose diet (Park et al, 1983(Park et al, , 1986 and increased even further by substituting hydrogenated coconut oil for corn oil in the sucrose diet .…”

Nutrient‐Gene Interactions in Mitochondrial Function: Vitamin A Needs Are Increased in BHE/Cdb Rats

“…One factor that could have affected our assessments of retinol status was the well-known strain difference in liver fat due to both an increase in de novo fatty acid synthesis and fatty acid mobilization. BHE/Cdb rats have twice the rate of fatty acid synthesis and 10 times more lipolysis than normal rats (6)(7)(8). In the presence of increased fatty acids, retinol is preferentially converted to retinyl esters instead of retinal and retinoic acid.…”

“…The BHE/Cdb rat is an animal model of mitochondrial diabetes with a maternally inherited mutation in the mitochondrially encoded ATPase 6 gene (1,2). Like humans with mitochondrial diabetes (3), young rats have hyperinsulinemia (4), insulin resistance (5), increased hepatic lipogenesis (6), increased gluco-neogenic capacity (7), and increased ketogenesis (7,8). As the rat ages, glucose-stimulated insulin secretion decreases (4,9), and, with age, impaired glucose tolerance develops (8).…”

Noninsulin-Dependent Diabetes Mellitus as a Mitochondrial Genomic Disease

“…Among these were: a two-fold increase in hepatic de novo fatty acid and cholesterol synthesis (1 12) and lipolysis (113), a 40% increase in gluconeogenesis (114), and a 20% reduction in ATP synthesis efficiency (115). In an experiment by Fowler and Berdanier (1 16), Sprague-Dawley rats were fed a sucrose-rich diet that contained 0.02% 3-(3,4-dichlorophenyl)-1,1 -dimethylurea (DCMU), a mild OXPHOS uncoupling agent.…”