Glucose production and storage in hepatocytes isolated from normal versus diabetic rats
The rates of glucose production and storage were compared in hepatocytes isolated from normal versus insulin-resistant diabetic rats. A single low-dose (40 mg/kg) IV injection of streptozotocin to 250 g rats resulted in a Type II diabetic animal model which was hyperglycemic with normal insulin levels. Addition of 8 mM /sup 14/C-lactate and 2 mM pyruvate to hepatocytes resulted in a linear increase in total glucose production (/sup 14/C-glucose and unlabeled glucose) and incorporation into glycogen measured over 120 min. The rate of gluconeogenesis was estimated from the production of /sup 14/C-glucose and the rate of glycogenolysis was estimated from the production of unlabeled glucose in cells incubated in the presence or absence of /sup 14/C-labelled substrate. There was not significant difference in total glucose production in hepatocytes isolated from normal versus diabetic rats, however, the contribution from gluconeogenesis versus glycogenolysis was significantly different. Following a 1 h incubation of cells from normal rats, 42% of the total glucose production was due to gluconeogenesis and 58% was due to glycogenolysis. In cells from diabetic rats, 83% of total glucose production was from gluconeogenesis and 17% from glycogenolysis. Also, incubation with /sup 14/C-lactate/pyruvate resulted in a 3.3-fold increase in /sup 14/C-glucose incorporation into glycogen in hepatocytes isolated from normal rats compared to diabetic rats. These data suggest that alterations occur in the rate-limiting enzymes responsible for glucose production and storage in hepatocytes isolated from a rat model of insulin-resistant Type II diabetes.
- Research Organization:
- Sandoz Research Institute, Hanover, NJ
- OSTI ID:
- 5877293
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
CARBOHYDRATES
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
COMPARATIVE EVALUATIONS
DIABETES MELLITUS
DISEASES
ENDOCRINE DISEASES
GLUCOSE
GLYCOGEN
GLYCOLYSIS
HEXOSES
HORMONES
INSULIN
ISOTOPE APPLICATIONS
KETO ACIDS
KINETICS
LABELLED COMPOUNDS
LACTATES
LIVER CELLS
MAMMALS
METABOLIC DISEASES
METABOLISM
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
PEPTIDE HORMONES
POLYSACCHARIDES
PYRUVIC ACID
RATS
REACTION KINETICS
RODENTS
SACCHARIDES
SOMATIC CELLS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES