Regulation of gluconeogenesis by alanine

1. In 48 h-starved 6-week-old rats the 14C incorporation in vivo into blood glucose from a constant-specific-radioactivity pool of circulating [14c]actateconfirmed that lactate is the preferred gluconeogenic substrate. 2. Increasing the blood [alanine] to that occurrring in the fed state increased 14C incorporation into blood glucose 2.3-fold from [14c]alanine and 1.7-fold from [14c]lactate. 3. When the blood [alanine] was increased to that in the fed state, the 14C incorporation into liver glycogen from circulating [14c]alanine or [14c]lactate increased 13.5- and 1.7-fold respectively. 4. The incorporation of 14C into blood acetoacetate and 3-hydroxybutyrate from a constant-specific-radioactivity pool of circulating [14c]oleate was virtually abolished by increasing the blood [alanine] to that existing in the fed state. However, the [acetoacetate] remained unchanged, whereas [3-hydroxybutyrate] decreased, although less rapidly than did its radiochemical concentration. 5. It is concluded that during starvation in 6-week-old rats, the blood [alanine] appears to influence ketogenesis for circulating unesterfied fatty acids and inversely affects gluconeogenesis from either lactate or alanine. A different pattern of gluconeogenesis may exist for alanine and lactate as evidenced by comparative 14C incorporation into liver glycogen and blood glucose.

Section: Discussionsupporting

confidence: 83%

Effect of L-alanine infusion on gluconeogenesis and ketogenesis in the rat in vivo

Özand¹,

Reed²,

Hawkins³

et al. 1978

“…R. Williamson et al, 1969). Alanine stimulates gluconeogenesis (Snell & Walker, 1973;Friedrichs & Schoner, 1974) and it was suggested that alanine causes a transient increase in the flow of reducing equivalents to the cytosol, leaving the mitochondria in a relatively oxidized state. This would explain the apparent disequilibrium between 3-hydroxybutyrate and acetoacetate, as acetoacetate formation would be favoured.…”

Section: Discussionmentioning

confidence: 99%

A possible mechanism for the anti-ketogenic action of alanine in the rat

Nosadini

Datta

Hodson

et al. 1980

1. The anti-ketogenic effect of alanine has been studied in normal starved and diabetic rats by infusing l-alanine for 90min in the presence of somatostatin (10mug/kg body wt. per h) to suppress endogenous insulin and glucagon secretion. 2. Infusion of alanine at 3mmol/kg body wt. per h caused a 70+/-11% decrease in [3-hydroxybutyrate] and a 58+/-9% decrease in [acetoacetate] in 48h-starved rats. [Glucose] and [lactate] increased, but [non-esterified fatty acid], [glycerol] and [3-hydroxybutyrate]/[acetoacetate] were unchanged. 3. Infusion of alanine at 1mmol/kg body wt. per h caused similar decreases in [ketone body] (3-hydroxybutyrate plus acetoacetate) in 24h-starved normal and diabetic rats, but no change in other blood metabolites. 4. Alanine [3mmol/kg body wt. per h] caused a 72+/-9% decrease in the rate of production of ketone bodies and a 57+/-8% decrease in disappearance rate as assessed by [3-(14)C]acetoacetate infusion. Metabolic clearance was unchanged, indicating that the primary effect of alanine was inhibition of hepatic ketogenesis. 5. Aspartate infusion at 6mmol/kg body wt. per h had similar effects on blood ketone-body concentrations in 48h-starved rats. 6. Alanine (3mmol/kg body wt. per h) caused marked increases in hepatic glutamate, aspartate, malate, lactate and citrate, phosphoenolpyruvate, 2-phosphoglycerate and glucose concentrations and highly significant decreases in [3-hydroxybutyrate] and [acetoacetate]. Calculated [oxaloacetate] was increased 75%. 7. Similar changes in hepatic [malate], [aspartate] and [ketone bodies] were found after infusion of 6mmol of aspartate/kg body wt. per h. 8. It is suggested that the anti-ketogenic effect of alanine is secondary to an increase in hepatic oxaloacetate and hence citrate formation with decreased availability of acetyl-CoA for ketogenesis. The reciprocal negative-feedback cycle of alanine and ketone bodies forms an important non-hormonal regulatory system.

“…Although no direct evidence has been provided in the present studies, ample evidence exists in the literature to support this working hypothesis. Alanine serves both as a gluconeogenic precursor (Aikawa et al, 1972;Snell & Walker, 1973) and stimulates gluconeogenesis in the rat (Friedrichs & Schoner, 1974). The rate of gluconeogenesis is considered to be regulated in part by the availability of reducing equivalents in the cytosol (J. R. D.…”

Section: Discussionmentioning

confidence: 99%

Hypoketonaemic effect of L-alamine. Specific decrease in blood concentrations of 3-hydroxybutyrate in the rat

Özand¹,

Reed²,

Girard³

et al. 1977

1. The injection of L-alanine (50-100 mg/kg) into 35-day-old rats that had been starveed for 48 h increased blood L-alanine concentration to values observed in fed animals and lowered the blood concentration of 3-hydroxybutyrate within 2 min. 2. This hypoketon aemic action of L-alanine was specific for 3-hydroxybutyrate, since the acetoacetate concentrations did not change significantly. 3. The decrease in 3-hydroxybutyrate elicited by L-alanine was not related to changes in the blood concentrations of insulin, glucagon, growth hormone, glucose, unesterified fatty acids, lactate or pyruvate. 4. The injection of L-alanine resulted in a decrease in total ketones that was apparently unrelated to their increased peripheral utilization. These results are interpreted as an anti-ketogenic action of L-alanine. 5. The data suggest that L-alamine lowers ketone-body formation in starved rats, possibly via an alteration in hepatic redox equilibrium.