Gluconeogenesis in mouse-liver slices

Abstract

1. The rate of gluconeogenesis from amino acids and other known precursors in slices of mouse liver after depletion of liver glycogen by means of phlorrhizin was high with l-lactate, pyruvate, glycerol, d-glyceraldehyde, dihydroxyacetone, d-fructose, sorbitol, xylitol, alpha-glycerophosphate, alanine, proline, threonine, serine and propionate. 2. The rate was unexpectedly low or even negligible with glutamate, aspartate, other glucogenic amino acids and the intermediates of the tricarboxylic acid cycle. 3. Glutamine and asparagine gave higher rates than the corresponding amino acids but still much lower rates than kidney cortex. 4. Livers of male mice gave much lower rates than livers of female mice. Kidney cortex showed no sex difference. 5. Livers of mice fed on a low-carbohydrate diet gave the same rates as livers of mice fed on a normal diet under the test conditions, i.e. 3hr. after an injection of phlorrhizin. 6. Much carbohydrate was formed from endogenous precursors and this was accompanied by release of ammonia and urea. 7. Gluconeogenesis in well-fed mice not treated with phlorrhizin was low. 8. Maximum rates were observed 3hr. after phlorrhizin treatment. 9. Prolonged phlorrhizin treatment did not prevent extensive deposition of liver glycogen, after an initial depletion. 10. Gluconeogenesis in livers of mice fed on a high-fat diet was relatively low. 11. Livers of alloxan-diabetic mice had a high carbohydrate content after phlorrhizin treatment, and gluconeogenesis from endogenous sources was about twice as high as in normal animals. Added substrates had about the same effect in normal and diabetic livers.

Stimulation of phosphoenolpyruvate carboxykinase (guanosine triphosphate) activity by low concentrations of circulating glucose in perfused rat liver

“…Gluconeogenic capacity ofthe liverfrom ratspreviously treated with nicotinic acid Krebs et al (1966) reported that the gluconeogenic capacity is inversely related to the amount of the glycogen store in mouse liver slices. On the other hand, the close relationship between phosphoenolpyruvate carboxykinase activity and gluconeogenic capacity is well established (see above).…”

“…The perfusion method was as described by Hems et al (1966). The perfusate (150ml) consisted of Krebs-Henseleit physiological saline (Krebs & Henseleit, 1932), bovine serum albumin powder (fraction V) previously filtered (in Krebs-Henseleit physiological saline) through Millipore filters (1.2pum pore size), and washed human erythrocytes stored for 30 days at 4°C in citrate-dextrose anticoagulant solution (Don Baxter, Glendale, Calif., U.S.A.).…”

Voluntary exercise under a food restriction condition decreases blood branched-chain amino acid levels, in addition to improvement of glucose and lipid metabolism, in db mice, animal model of type 2 diabetes

“…In exercising db mice, the decrease in arginine and ornithine through possible incorporation into the liver, intermediates of the urea cycle, suggests an important role in ammonia detoxification [34]. Proline and alanine (vs. Se-db mice, P = 0.06), which decrease with exercise, may be utilized efficiently to form glucose in the liver [35]. However, it remains to be elucidated whether exercise enhanced hepatic gluconeogenesis.…”

Tritium as a tracer for mitochondrial and cytosolic reducing hydrogen in the kidney cortex

“…125 mg segments were incubated in 2 ml of the phosphate-salts buffer of Krebs et al [7] for 2 hr at * This work was supported by U.S. Public Health Service Grant no. AM-12604 and General Research Support Grant no.…”

“…RR-05468. 7 We use the convention which numbers the citric and isocitric acids in the same fashion. Thus acetyl CoA furnishes C-4 and C-5 of citrate in the mammalian citrate synthase reaction.…”