Effects of insulin on perfused liver from streptozotocin-diabetic and untreated rats: /sup 13/C NMR assay of pyruvate kinase flux
The effects of insulin in vitro on perfused liver from streptozotocin-diabetic rats and their untreated littermates during gluconeogenesis from either (3-/sup 13/C)alanine + ethanol or (2-/sup 13/C)pyruvate + NH/sub 4/Cl + ethanol were studied by /sup 13/C NMR. A /sup 13/C NMR determination of the rate of pyruvate kinase flux under steady-state conditions of active gluconeogenesis was developed; this assay includes a check on the reuse of recycled pyruvate. The preparations studied provided gradations of pyruvate kinase flux within the confines of the assay's requirement of active gluconeogenesis. By this determination, the rate of pyruvate kinase flux was 0.74 +/- 0.04 of the gluconeogenic rate in liver from 24-h-fasted controls; in liver from 12-h fasted controls, relative pyruvate kinase flux increased to 1.0 +/- 0.2. In diabetic liver, this flux was undetectable by the authors NMR method. Insulin's hepatic influence in vitro was greatest in the streptozotocin model of type 1 diabetes: upon treatment of diabetic liver with 7 nM insulin in vitro, a partial reversal of many of the differences noted between diabetic and control liver was demonstrated by /sup 13/C NMR. A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls. By way of comparison, the effects of ischemia on diabetic liver were studied by /sup 13/C NMR to test whether changes in allosteric effectors under these conditions could also increase pyruvate kinase flux. A large increase in this activity was demonstrated in ischemic diabetic liver.
- Research Organization:
- Merck Sharp and Dohme Research Labs., Rahway, NJ
- OSTI ID:
- 6616726
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:2; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
/sup 13/C NMR study of effects of fasting and diabetes on the metabolism of pyruvate in the tricarboxylic acid cycle and of the utilization of pyruvate and ethanol in lipogenesis in perfused rat liver
Estimation of liver glucose metabolism after refeeding
Related Subjects
550601* -- Medicine-- Unsealed Radionuclides in Diagnostics
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
ALANINES
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
ANTINEOPLASTIC DRUGS
BIOLOGICAL EFFECTS
BIOLOGICAL PATHWAYS
BODY
CARBON 13
CARBON ISOTOPES
CARBOXYLIC ACIDS
DIABETES MELLITUS
DIGESTIVE SYSTEM
DISEASES
DRUGS
ENDOCRINE DISEASES
ENZYMES
EVEN-ODD NUCLEI
FASTING
GLANDS
HORMONES
IN VITRO
INSULIN
ISOTOPES
KETO ACIDS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAGNETIC RESONANCE
MAMMALS
METABOLIC DISEASES
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PERFUSED TISSUES
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PYRUVIC ACID
RADIOENZYMATIC ASSAY
RATS
RESONANCE
RODENTS
STABLE ISOTOPES
STREPTOZOCIN
TISSUES
TRANSFERASES
VERTEBRATES