Glucose metabolism in renal tubular function

Ross, Brian D.; Espinal, J.; Silva, Patricio

doi:10.1038/ki.1986.8

Cited by 84 publications

(70 citation statements)

References 111 publications

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“…Noteworthy, the TAL has a higher capacity for glycolysis than the proximal tubule, with higher expression of glycolytic enzymes. 7 This expression was further augmented in Vhl knockout animals and was preserved after ischemia-reperfusion. We also found increased renal lactate concentrations in knockout animals, suggesting that a higher glycolytic capacity supported TAL function and permitted ATP-consuming transport processes and maintenance of the osmotic gradient in the renal medulla.…”

Section: Discussionmentioning

confidence: 87%

“…4 -6 Vulnerability of both segments has partially been explained by their low capacity for anaerobic glycolysis, although TAL cells have comparatively higher levels of glycolytic gene expression than proximal tubules. 2,6,7 The relative importance of both segments in the pathogenesis of AKI remains controversial and may depend on the models used. 4 Inhibition of sodium reabsorption and hence oxygen consumption in TALs using furosemide reduced TAL injury in some, 8 -10 but not all experimental settings [11][12][13][14][15] and failed to reduce the incidence of AKI in humans.…”

mentioning

confidence: 99%

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Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury

Schley

Klanke²,

Schödel³

et al. 2011

Journal of the American Society of Nephrology

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Hypoxia-inducible transcription factors (HIF) protect cells against oxygen deprivation, and HIF stabilization before ischemia mitigates tissue injury. Because ischemic acute kidney injury (AKI) often involves the thick ascending limb (TAL), modulation of HIF in this segment may be protective. Here, we generated mice with targeted TAL deletion of the von Hippel-Lindau protein (Vhl), which mediates HIF degradation under normoxia, using Tamm-Horsfall protein (Thp)-driven Cre expression. These mice showed strong expression of HIF-1␣ in TALs but no changes in kidney morphology or function under control conditions. Deficiency of Vhl in the TAL markedly attenuated proximal tubular injury and preserved TAL function following ischemia-reperfusion, which may be partially a result of enhanced expression of glycolytic enzymes and lactate metabolism. These results highlight the importance of the thick ascending limb in the pathogenesis of AKI and suggest that pharmacologically targeting the HIF system may have potential to prevent and mitigate AKI.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury

Schley

Klanke²,

Schödel³

et al. 2011

Journal of the American Society of Nephrology

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“…Renal functions in glucose metabolism include the transfer of glucose from the filtrate across epithelial cell membranes into the bloodstream, the de novo synthesis of glucose for release into the bloodstream, and the utilization of glucose in both glycolytic and oxidative pathways (9,10,20). These different activities are compartmentalized in different segments of the nephron, as has been shown by the mapping of gluconeogenic and glycolytic enzymes to different segments ( 10).…”

Section: Discussionmentioning

confidence: 99%

Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney.

Chin¹,

Zhou²,

Bondy³

1993

J. Clin. Invest.

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In situ hybridization was used to map cellular patterns of gene expression for facilitative glucose transporters (GTs) 1-5 in the developing and adult rat kidney. GT3 was not detected. GTl mRNA was present in the proximal straight tubule (PST), distal nephron and collecting duct. GT2 mRNA was localized in both proximal convoluted and PST, while GT5 mRNA was detected only in the PST. GT4 mRNA and immunoreactivity were focally localized in the thick ascending limb of Henle's loop and were coexpressed with IGF-I. Thus, each of the four different isoforms demonstrated a distinct renal distribution, with GTs 1, 2, and 5 coexpressed in the PST. Renal GT1 and GT5 gene expression were unchanged throughout development, while GT2 was most abundant before weaning and GT4 was first detected after weaning. Only GT4 appeared to be hormonally regulated: It was decreased after hypophysectomy and increased after vasopressin treatment, but was not affected by 1 or 4 d of insulinopenic diabetes mellitus. The coexpression of GT4 and IGF-I in the thick ascending limb segment of the nephron suggests a novel autocrine/paracrine mechanism by which cells may control local fuel economy independently from that of the larger structure to which they belong and from the systemic hormonal milieu. (J.

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“…Although it was surprising to find opposing gradients of IGFBP-1 and PEPCK mRNA in the liver acinus, different regions of expression of these proteins also occur in the kidney. IGFBP-1 is expressed at the highest levels in the medullary thick ascending limb of Henle (Chin et al 1992), while the proximal tubule is the site of higher PEPCK expression (Ross et al 1986). It is even more interesting to note that these regions are homologous to the liver zones with respect to their glucose metabolism.…”

Section: Figurementioning

confidence: 98%

“…perivenous zone), while the proximal tubule is the site of gluconeogenesis in the kidney (i.e. periportal zone) (Ross et al 1986).…”

Section: Figurementioning

confidence: 99%

Differential expression of IGF-I and IGF-binding protein-1 and -2 in periportal and perivenous zones of rat liver

Hazel

Nordqvist²,

Hall³

et al. 1998

Journal of Endocrinology

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IGF-I has important roles in regulating growth and metabolism. Circulating IGF-I is bound to specific binding proteins (IGFBP-1 to -6), with hepatocytes containing IGF-I, IGFBP-1 and -2 mRNA. Although many hepatic proteins are regionally expressed in the liver acinus, no studies have reported zonation of IGF protein expression. In this study we investigated the pattern of hepatic mRNA for the IGF proteins, vs the previously reported periportal gradient of phosphoenolpyruvate carboxykinase (PEPCK) expression. In situ hybridisation was used to analyse IGF-I, IGFBP-1, -2 and PEPCK mRNA in female SpragueDawley rats fed diets containing low (6%), normal (21%) or high (35%) protein. We report for the first time that IGFBP-1 and -2 and IGF-I are differentially expressed in the liver acinus. In the normal-and high-protein groups, levels of IGFBP-1 mRNA were higher in the perivenous region, i.e. the opposite gradient to PEPCK, with a higher gradient of IGFBP-1 expression in the high-protein group. In contrast, IGFBP-2 had a similar pattern to PEPCK, and a periportal gradient of IGF-I mRNA was also seen in the low-protein group. Using computerised image analysis, levels of IGFBP-1 and -2 mRNA were elevated 2-and 10-fold respectively, in the low-vs normal-protein groups. The level of IGF-I mRNA was reduced to 65% of normal, with circulating IGF-I levels at 30% and insulin levels 39% of normal. These results demonstrate that hepatocytes are a heterogeneous population with respect to regulation of IGF proteins, having specific expression patterns dependent on the position of the hepatocyte within the liver acinus.

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Glucose metabolism in renal tubular function

Cited by 84 publications

References 111 publications

Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury

Hypoxia-Inducible Transcription Factors Stabilization in the Thick Ascending Limb Protects against Ischemic Acute Kidney Injury

Anatomical and developmental patterns of facilitative glucose transporter gene expression in the rat kidney.

Differential expression of IGF-I and IGF-binding protein-1 and -2 in periportal and perivenous zones of rat liver

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