Regulation of gluconeogenesis by glutamine in normal postabsorptive humans

Abstract

There is evidence that glutamine may act as a regulator of protein, free fatty acid, and glycogen metabolism. To test the hypothesis that glutamine may act as a physiological regulator of gluconeogenesis, we infused 16 normal postabsorptive volunteers with glutamine at a rate (11.4 micromol kg(-1) x min(-1)) estimated to approximate its appearance in plasma after a protein meal and assessed changes in production of glucose from glutamine, systemic glucose appearance and disposal, and uptake and release of glucose, glutamine, and alanine by forearm skeletal muscle. Although infusion of glutamine increased plasma glutamine concentration and turnover only threefold (from 0.63 +/- 0.03 to 1.95 +/- 0.10 mmol/l and from 5.43 +/- 0.24 to 14.85 +/- 0.66 micromol x kg(-1) x min(-1), respectively; P < 0.001), formation of glucose from glutamine increased sevenfold from 0.55 +/- 0.03 to 3.74 +/- 0.28 micromol x kg(-1) x min(-1) (P < 0.001). Formation of glucose from alanine was also stimulated (0.52 +/- 0.05 vs. 0.75 +/- 0.04 micromol x kg(-1) x min(-1); P < 0.001) in the absence of a change in plasma alanine concentration. Furthermore, glutamine infusion decreased its own de novo synthesis (4.55 +/- 0.22 vs. 2.81 +/- 0.62 micromol x kg(-1) x min(-1);P < 0.02) while increasing that of alanine (2.82 +/- 0.32 vs. 3.56 +/- 0.32 micromol x kg(-1) x min(-1); P < 0.002). Systemic glucose appearance, systemic glucose disposal, and forearm balance of glucose and alanine were not altered. Because the stimulatory effects of glutamine on gluconeogenesis occurred in the absence of changes in plasma insulin and glucagon levels, these results provide evidence that, in humans, glutamine may act both as a substrate and as a regulator of gluconeogenesis as well as a modulator of its own metabolism.

Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?

“…This has been shown using intravenous lactate [70,102,103] alanine [68,104], glutamine [69], glycerol [68,71,105], and fructose [35] (Table 3).…”

“…However, several studies using different gluconeogenic substrates such as amino acids, lactate, glycerol and the monosaccharides, fructose and galactose, have shown that there is little change in glucose production in the post-absorptive state, despite increased availability of substrates [68][69][70][71][72][73].…”

“…The constancy of glucose production rates in this setting cannot be explained by a hormonally mediated mechanism. Intravenous infusion of lactate, alanine, glutamine, or glycerol, did not significantly affect the insulin or glucagon concentrations [68,69,102]. In addition, using an insulin, growth hormone, glucagon clamp technique and a lactate infusion protocol, an increase in glucagon concentration stimulated an increase in lactate to glucose conversion, but did not increase the overall glucose production rate [106].…”

Majority of Dietary Glutamine Is Utilized in First Pass in Preterm Infants

“…Glutamine is synthesized from amination of glutamate via glutamine synthetase and catabolized via deamination back to glutamate via glutaminase. Glutamine carbon enters the TCA cycle as ␣-ketoglutarate and is used for energy or for formation of new glucose (28). Glutamate itself can be used as precursor for glutathione, the major intracellular anti-oxidant.…”

Nutrition from the Inside Out

“…During this period, I also reestablished my long-standing collaboration with Jack Gerich in a series of experiments demonstrating how the enhanced information content available in studies employing both stable-and radio-tracer-labeled gluconeogenic substrates results in a more comprehensive understanding of the gluconeogenic process in humans (36,37,119,129,130,147).…”