fumarates and Starvation

1. Rates of insulin secretion, glucose utilization, lactate output, incorporation of glucose into glycogen, contents of glucose 6-phosphate, fructose 1,6-diphosphate and ATP, and maximally extractable enzyme activities of hexokinase, high-K(m) glucose-phosphorylating activity (;glucokinase'), glucose 6-phosphatase and unspecific acid phosphatase were measured in isolated pancreatic islets from fed and 48-h-starved mice. 2. In the fed state insulin secretion from isolated islets was increased five- to six-fold when the extracellular glucose concentration was raised from 2.5mm to 16.7mm; 5mm-caffeine potentiated this effect. The secretory response to glucose of islets from mice starved for 48h was diminished at all glucose concentrations from 2.5mm up to approx. 40mm. Very high glucose concentrations (60mm and above) restored the secretory response to that found in the fed state, suggesting that the K(m) value for the overall secretory process had been increased (approx. fourfold) by starvation. Addition of 5mm-caffeine to islets from starved mice also restored the insulin secretory response to 2.5-16.7mm-glucose to normal values. 3. Extractable hexokinase, ;glucokinase', glucose 6-phosphatase and unspecific phosphatase activities were not changed by starvation. 4. Glucose utilization and glycolysis (measured as the rate of formation of (3)H(2)O from [5-(3)H]glucose over a 2h period) was decreased in islets from starved mice at all glucose concentrations up to approx. 55mm. At still higher glucose concentrations up to approx. 100mm, there was no difference between the fed and starved state, suggesting that the K(m) value for the rate-limiting glucose phosphorylation had been increased (approx. twofold) by starvation. Preparation of islets omitting substrates (glucose, pyruvate, fumarate and glutamate) from the medium during collagenase treatment lowered the glucose utilization measured subsequently at 16.7mm-glucose by 38 and 30% in islets from fed and starved mice respectively. Also the 2h lactate output by the islets at 16.7mm extracellular glucose was diminished by starvation. Incorporation of glucose into glycogen was extremely low, but the rate of incorporation was more than doubled by starvation. 5. After incubation for 30min at 16.7mm-glucose the content of glucose 6-phosphate was unchanged by starvation, that of ATP was increased and the concentration of (fructose 1,6-diphosphate plus triose phosphates) was decreased. 6. Possible mechanisms behind t

Topics: Acid Phosphatase; Adenosine Triphosphate; Animals; Caffeine; Fructosephosphates; Fumarates; Glucokinase; Glucose; Glucose-6-Phosphatase; Glucosephosphates; Glutamates; Glycogen; Glycolysis; Hexokinase; In Vitro Techniques; Insulin; Insulin Secretion; Islets of Langerhans; Kinetics; Male; Mice; NADP; Pyruvates; Starvation; Tritium

1. The effect of Ca(2+), glucagon, adrenaline and adenosine 3':5'-cyclic monophosphate on gluconeogenesis by rat kidney-cortex slices was studied. 2. Glucose formation from a range of substrates, with the exception of glycerol, was increased by an increase in extracellular Ca(2+) concentration. 3. Hormones and adenosine 3':5'-cyclic monophosphate, at low Ca(2+) concentrations, stimulated glucose production from several substrates, but not from glycerol, fructose, malate or fumarate. 4. Hormonal stimulation was not detected in the absence of Ca(2+) or at 2.5mm-Ca(2+). 5. Ca(2+), hormones and adenosine 3':5'-cyclic monophosphate had no effect on phosphoenolpyruvate carboxylase activity. 6. It is proposed that Ca(2+) and adenosine 3':5'-cyclic monophosphate-mediated hormone action activate the same rate-limiting step in gluconeogenesis: this step is tentatively identified as the rate of transfer of substrates across the mitochondrial membrane.

Topics: Animals; Butyrates; Calcium; Cyclic AMP; Dose-Response Relationship, Drug; Epinephrine; Fumarates; Glucagon; Gluconeogenesis; Glutamine; Kidney; Kidney Cortex; Kinetics; Lactates; Malates; Male; Models, Biological; Phosphoenolpyruvate Carboxykinase (GTP); Rats; Spectrophotometry, Ultraviolet; Starvation; Succinates

Topics: 5-Aminolevulinate Synthetase; Acetamides; Acetone; Acetyl Coenzyme A; Allylisopropylacetamide; Animals; Female; Fumarates; Levulinic Acids; Liver; Malate Dehydrogenase; Mitochondria, Liver; Oxidoreductases; Pyruvate Carboxylase; Rats; Starvation; Succinates; Time Factors

Topics: Anesthesia; Animals; Blood Glucose; Carbon Isotopes; Chromatography, Gas; Citrates; Diabetes Mellitus; Diabetes Mellitus, Experimental; Fumarates; Glycosuria; Guinea Pigs; Hydroxybutyrates; Insulin Antibodies; Ketoglutaric Acids; Liver; Malates; Pyruvates; Rats; Starvation; Streptozocin; Succinates; Unconsciousness

Topics: Adrenal Cortex Hormones; Adrenal Insufficiency; Adrenalectomy; Citric Acid Cycle; Cold Temperature; Fumarates; Pharmacology; Rats; Research; Starvation; Stress, Physiological; Succinates; Succinic Acid; Vitamin A; Vitamin K; Vitamins