Evidence that Alpha-1-Adrenergic Stimuli Specifically Increase Gluconeogenesis of the Isolated Proximal Convoluted Tubule in the Rat

Nakada, J; Yamada, Hideo; Endou, Hitoshi

doi:10.1159/000173086

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Given the well accepted view that adrenaline and noradrenaline stimulate gluconeogenesis from lactate or pyruvate [30][31][32][33] and from glutamine or 2-oxoglutarate [30,31,44] in isolated rat kidney cortex slices or tubules via α-adrenergic receptors [31,45,46], it may appear at first sight surprising that similar observations were not made with isolated human proximal tubules in the present study. Careful examination of the experimental conditions used by other authors reveal that these stimulatory effects were observed with low, unphysiological external calcium concentrations [30,32], but not with a physiological calcium concentration (2.5 mM) [30] similar to that used in the present study.…”

Section: Failure Of Adrenaline To Stimulate Gluconeogenesis From Lactsupporting

confidence: 53%

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

Conjard¹,

Martin²,

Guitton³

et al. 2001

Biochem. J.

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Recent studies in vivo have suggested that, in humans in the postabsorptive state, the kidneys contribute a significant fraction of systemic gluconeogenesis, and that the stimulation of renal gluconeogenesis may fully explain the increase in systemic gluconeogenesis during adrenaline infusion. Given the potential importance of human renal gluconeogenesis in various physiological and pathophysiological situations, we have conducted a study in vitro to further characterize this metabolic process and its regulation. For this, successive segments (S1, S2 and S3) of human proximal tubules were dissected and incubated with physiological concentrations of glutamine or lactate, two potential gluconeogenic substrates that are taken up by the human kidney in vivo, and glucose production was measured. The effects of adrenaline, noradrenaline and cAMP, a well established stimulator of gluconeogenesis in animal kidney tubules, were also studied in suspensions of human renal proximal tubules. The results indicate that the three successive segments have about the same capacity to synthesize glucose from glutamine; by contrast, the S2 and S3 segments synthesize more glucose from lactate than the S1 segment. In the S2 and S3 segments, lactate appears to be a better gluconeogenic precursor than glutamine. The addition of cAMP, but not of adrenaline or noradrenaline, led to the stimulation of gluconeogenesis from lactate and glutamine by human proximal tubules. These results indicate that, in the human kidney in vivo, lactate might be the main gluconeogenic precursor, and that the stimulation of renal gluconeogenesis observed in vivo upon adrenaline infusion may result from an indirect action on the renal proximal tubule.

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Section: Failure Of Adrenaline To Stimulate Gluconeogenesis From Lactsupporting

confidence: 53%

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

Conjard¹,

Martin²,

Guitton³

et al. 2001

Biochem. J.

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Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans

Meyer¹,

Stümvoll

Welle

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Splanchnic and renal net balance measurements indicate that lactate and glycerol may be important precursors for epinephrine-stimulated gluconeogenesis (GNG) in liver and kidney, but the effects of epinephrine on their renal and hepatic conversion to glucose in humans have not yet been reported. We therefore used a combination of renal balance and isotopic techniques in nine postabsorptive volunteers to measure systemic and renal GNG from these precursors before and during a 3-h infusion of epinephrine (270 pmol. kg-1. min-1) and calculated hepatic GNG as the difference between systemic and renal rates. During infusion of epinephrine, renal and hepatic GNG from lactate increased 4- to 6-fold and accounted for approximately 85 and 70% of renal and hepatic glucose release, respectively, at the end of study; renal and hepatic GNG from glycerol increased approximately 1.5- to 2-fold and accounted for approximately 7-9% of renal and hepatic glucose release at the end of study. The increased renal GNG from lactate and glycerol was due not only to their increased renal uptake (approximately 3.3- and 1.4-fold, respectively) but also increased renal gluconeogenic efficiency (approximately 1.8- and 1.5-fold). The increased renal uptake of lactate and glycerol was wholly due to their increased arterial concentrations, since their renal fractional extraction remained unchanged and renal blood flow decreased. We conclude that 1) lactate is the predominant precursor for epinephrine-stimulated GNG in both liver and kidney, 2) hepatic and renal GNG from lactate and glycerol are similarly sensitive to stimulation by epinephrine, and 3) epinephrine increases renal GNG from lactate and glycerol by increasing substrate availability and the gluconeogenic efficiency of the kidney.

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Landscape of GPCR expression along the mouse nephron

Poll

Chen

Chou

et al. 2021

American Journal of Physiology-Renal Physiology

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Kidney transport and other renal functions are regulated by multiple G protein-coupled receptors (GPCRs) expressed along the renal tubule. The rapid, recent appearance of comprehensive unbiased gene expression data in the various renal tubule segments, chiefly RNA-seq and protein mass spectrometry data, has provided a means of identifying patterns of GPCR expression along the renal tubule. To allow for comprehensive mapping, we first curated a comprehensive list of GPCRs in the genomes of mice, rats, and humans (https://hpcwebapps.cit.nih.gov/ESBL/Database/GPCRs/), using multiple online data sources. We used this list to mine segment-specific and cell-type specific expression data from RNA-seq studies in microdissected mouse tubule segments to identify GPCRs that are selectively expressed in discrete tubule segments. Comparisons of these mapped mouse GPCRs with other omics datasets as well as functional data from isolated perfused tubule and micro-puncture studies confirms patterns of expression for well-known receptors and identifies poorly studied GPCRs that are likely to play roles in regulation of renal tubule function. Thus, we provide data resources for GPCR expression across the renal tubule, highlighting both well-known GPCRs and understudied receptors in order to provide guidance for future studies.

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Evidence that Alpha-1-Adrenergic Stimuli Specifically Increase Gluconeogenesis of the Isolated Proximal Convoluted Tubule in the Rat

Cited by 3 publications

References 23 publications

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

Gluconeogenesis from glutamine and lactate in the isolated humanrenal proximal tubule: longitudinal heterogeneity and lack of response to adrenaline

Relative importance of liver, kidney, and substrates in epinephrine-induced increased gluconeogenesis in humans

Landscape of GPCR expression along the mouse nephron

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