Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats

Jesus Dominguez, Kathy Camp, Lidia Maianu, Hilary Feister, W. Timothy Garvey

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The renal reabsorption of glucose is mediated by two major classes of transporters. Initially, luminal glucose is concentrated in tubules by Na+-glucose cotransporters (Na+-GLUT). Afterwards, glucose reaches the blood space through facilitative glucose transporters, low-Michaelis constant (Km) GLUT1 and high-Km GLUT2. Hence, the transtubular flux of glucose could be impaired in hyperglycemia because the outwardly directed glucose gradient, from tubule to blood, is potentially lowered. However, in diabetic rats, transtubular glucose flux is not reduced but increased. In this work the molecular mechanism underlying this adaptation was examined. We tested the hypothesis that upregulation of renal tubular high-Km GLUT2 gene may compensate for the decrease in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA steady-state levels were reduced, and GLUT2 protein and mRNA levels were increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced diabetes. These molecular adaptations were associated with augmented facilitative glucose flux. In summary, changes in GLUT1 and GLUT2 gene expression are important to the preservation of renal glucose reabsorption in hyperglycemia.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume266
Issue number2 35-2
StatePublished - Feb 1994

Fingerprint

Proximal Kidney Tubule
Glucose
Hyperglycemia
Blood Glucose
Glucose Transporter Type 2
Glucose Transporter Type 1
Messenger RNA
Experimental Diabetes Mellitus
Facilitative Glucose Transport Proteins
Up-Regulation
Kidney
Gene Expression

Keywords

  • Diabetes nephropathy
  • Glucose transporter
  • Kidney
  • Nephromegaly
  • Sodium-glucose cotransporter

ASJC Scopus subject areas

  • Physiology

Cite this

Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats. / Dominguez, Jesus; Camp, Kathy; Maianu, Lidia; Feister, Hilary; Garvey, W. Timothy.

In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology, Vol. 266, No. 2 35-2, 02.1994.

Research output: Contribution to journalArticle

@article{e6f47cbfe92745ce86f80a40b2dc8853,
title = "Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats",
abstract = "The renal reabsorption of glucose is mediated by two major classes of transporters. Initially, luminal glucose is concentrated in tubules by Na+-glucose cotransporters (Na+-GLUT). Afterwards, glucose reaches the blood space through facilitative glucose transporters, low-Michaelis constant (Km) GLUT1 and high-Km GLUT2. Hence, the transtubular flux of glucose could be impaired in hyperglycemia because the outwardly directed glucose gradient, from tubule to blood, is potentially lowered. However, in diabetic rats, transtubular glucose flux is not reduced but increased. In this work the molecular mechanism underlying this adaptation was examined. We tested the hypothesis that upregulation of renal tubular high-Km GLUT2 gene may compensate for the decrease in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA steady-state levels were reduced, and GLUT2 protein and mRNA levels were increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced diabetes. These molecular adaptations were associated with augmented facilitative glucose flux. In summary, changes in GLUT1 and GLUT2 gene expression are important to the preservation of renal glucose reabsorption in hyperglycemia.",
keywords = "Diabetes nephropathy, Glucose transporter, Kidney, Nephromegaly, Sodium-glucose cotransporter",
author = "Jesus Dominguez and Kathy Camp and Lidia Maianu and Hilary Feister and Garvey, {W. Timothy}",
year = "1994",
month = "2",
language = "English",
volume = "266",
journal = "American Journal of Physiology",
issn = "0193-1857",
publisher = "American Physiological Society",
number = "2 35-2",

}

TY - JOUR

T1 - Molecular adaptations of GLUT1 and GLUT2 in renal proximal tubules of diabetic rats

AU - Dominguez, Jesus

AU - Camp, Kathy

AU - Maianu, Lidia

AU - Feister, Hilary

AU - Garvey, W. Timothy

PY - 1994/2

Y1 - 1994/2

N2 - The renal reabsorption of glucose is mediated by two major classes of transporters. Initially, luminal glucose is concentrated in tubules by Na+-glucose cotransporters (Na+-GLUT). Afterwards, glucose reaches the blood space through facilitative glucose transporters, low-Michaelis constant (Km) GLUT1 and high-Km GLUT2. Hence, the transtubular flux of glucose could be impaired in hyperglycemia because the outwardly directed glucose gradient, from tubule to blood, is potentially lowered. However, in diabetic rats, transtubular glucose flux is not reduced but increased. In this work the molecular mechanism underlying this adaptation was examined. We tested the hypothesis that upregulation of renal tubular high-Km GLUT2 gene may compensate for the decrease in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA steady-state levels were reduced, and GLUT2 protein and mRNA levels were increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced diabetes. These molecular adaptations were associated with augmented facilitative glucose flux. In summary, changes in GLUT1 and GLUT2 gene expression are important to the preservation of renal glucose reabsorption in hyperglycemia.

AB - The renal reabsorption of glucose is mediated by two major classes of transporters. Initially, luminal glucose is concentrated in tubules by Na+-glucose cotransporters (Na+-GLUT). Afterwards, glucose reaches the blood space through facilitative glucose transporters, low-Michaelis constant (Km) GLUT1 and high-Km GLUT2. Hence, the transtubular flux of glucose could be impaired in hyperglycemia because the outwardly directed glucose gradient, from tubule to blood, is potentially lowered. However, in diabetic rats, transtubular glucose flux is not reduced but increased. In this work the molecular mechanism underlying this adaptation was examined. We tested the hypothesis that upregulation of renal tubular high-Km GLUT2 gene may compensate for the decrease in the tubule to blood glucose gradient. In rat tubules, GLUT1 protein and mRNA steady-state levels were reduced, and GLUT2 protein and mRNA levels were increased in rats after 2, 3, and 4 wk of uncontrolled streptozotocin-induced diabetes. These molecular adaptations were associated with augmented facilitative glucose flux. In summary, changes in GLUT1 and GLUT2 gene expression are important to the preservation of renal glucose reabsorption in hyperglycemia.

KW - Diabetes nephropathy

KW - Glucose transporter

KW - Kidney

KW - Nephromegaly

KW - Sodium-glucose cotransporter

UR - http://www.scopus.com/inward/record.url?scp=0028280105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028280105&partnerID=8YFLogxK

M3 - Article

C2 - 8141329

AN - SCOPUS:0028280105

VL - 266

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0193-1857

IS - 2 35-2

ER -