Role of the GLUT 2 Glucose Transporter in the Response of the L-type Pyruvate Kinase Gene to Glucose in Liver-derived Cells

Antoine, B; Lefrançois‐Martinez, Anne‐Marie; Guillou, Gilles Le; Leturque, Armelle; Vandewalle, Alain; Kahn, Axel

doi:10.1074/jbc.272.29.17937

Cited by 38 publications

(28 citation statements)

References 38 publications

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“…It seems likely that the main role of GLUT2 in gluconeogenic tissues, such as the liver, is to allow for a rapid equilibrium between intra-and extracellular glucose, in particular an easy secretion of glucose under gluconeogenic conditions. In hepatoma cells devoid of GLUT2 and cultured without glucose, the concentration of intracellular glucose 6-phosphate remains high, thus explaining the continuous stimulation of glucose-sensitive genes and consequent loss of glucose responsiveness (7). Accordingly, in GLUT2 Ϫ/Ϫ mice the intracellular glucose 6-phosphate concentration is high in fasting animals (8,9); and in patients with mutation in the GLUT2 gene (the Fanconi-Bickel syndrome), there is an associated accumulation of intrahepatic glycogen (10).…”

Section: The Glucose Signaling Pathwaymentioning

confidence: 99%

Glucose Regulation of Gene Transcription

Vaulont

Vasseur-Cognet

Kahn

2000

Journal of Biological Chemistry

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256

166

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Section: The Glucose Signaling Pathwaymentioning

confidence: 99%

Glucose Regulation of Gene Transcription

Vaulont

Vasseur-Cognet

Kahn

2000

Journal of Biological Chemistry

Self Cite

256

166

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“…For example, mice exhibit sex-related differences in metabolism of branched-chain lipids [49], in hepatic regulation of cholesterol metabolism [50], in the hepatic lipid accumulation in mice lacking the L-FABP gene product only [22], as well as the response to a high-cholesterol diet in L-FABP gene-ablated mice [20;51] To better resolve the impact of these proteins on hepatobiliary bile acid metabolism in female mice, studies were undertaken comparing female mice singly ablated in L-FABP (LKO), singly ablated in SCP-2/SCP-x (DKO), or ablated in both L-FABP and SCP-2/SCP-x (TKO). The data herein demonstrate that L-FABP had a much greater impact on hepatic retention of bile acids while SCP-2/SCP-x more broadly affected biliary bile acid and phospholipid levels.…”

Section: Introductionmentioning

confidence: 99%

Relative contributions of L-FABP, SCP-2/SCP-x, or both to hepatic biliary phenotype of female mice

Martin

Landrock

et al. 2015

Archives of Biochemistry and Biophysics

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Both sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x) and liver fatty acid binding protein (L-FABP) have been proposed to function in hepatobiliary bile acid metabolism/accumulation. To begin to address this issue, the impact of ablating L-FABP (LKO) or SCP-2/SCP-x (DKO) individually or both together (TKO) was examined in female mice. Biliary bile acid levels were decreased in LKO, DKO, and TKO mice; however, hepatic bile acid concentration was decreased in LKO mice only. In contrast, biliary phospholipid level was decreased only in TKO mice, while biliary cholesterol levels were unaltered regardless of phenotype. The loss of either or both genes increased hepatic expression of the major bile acid synthetic enzymes (CYP7A1 and/or CYP27A1). Loss of L-FABP and/or SCP-2/SCP-x genes significantly altered the molecular composition of biliary bile acids, but not the proportion of conjugated/unconjugated bile acids or overall bile acid hydrophobicity index. These data suggested that L-FABP was more important in hepatic retention of bile acids, while SCP-2/SCP-x more broadly affected biliary bile acid and phospholipid levels.

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“…Glucose controls many functions of ␤ cells; in particular, it stimulates the transcription of several genes, such as those for insulin (29), Lpyruvate kinase (30), or macrophage migration inhibitory factor (31), and the translation of preexisting mRNAs, such as those for insulin (32) and the proconvertases PC1/3 and PC2 (33). A specific requirement for GLUT2, as compared with GLUT1, has indeed been reported in the control by glucose of L-pyruvate kinase gene expression in hepatocytes (34).…”

Section: Normal ␤-Cell Glucose Sensing With Glut1 or Glut2mentioning

confidence: 99%

Transgenic Reexpression of GLUT1 or GLUT2 in Pancreatic β Cells Rescues GLUT2-null Mice from Early Death and Restores Normal Glucose-stimulated Insulin Secretion

Thorens¹,

Guillam²,

Beermann³

et al. 2000

Journal of Biological Chemistry

175

139

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GLUT2-null mice are hyperglycemic, hypoinsulinemic, hyperglucagonemic, and glycosuric and die within the first 3 weeks of life. Their endocrine pancreas shows a loss of first phase glucose-stimulated insulin secretion (GSIS) and inverse ␣ to ␤ cell ratio. Here we show that reexpression by transgenesis of either GLUT1 or GLUT2 in the pancreatic ␤ cells of these mice allowed mouse survival and breeding. The rescued mice had normal-fed glycemia but fasted hypoglycemia, glycosuria, and an elevated glucagon to insulin ratio. Glucose tolerance was, however, normal. In vivo, insulin secretion assessed following hyperglycemic clamps was normal. In vitro, islet perifusion studies revealed that first phase of insulin secretion was restored as well by GLUT1 or GLUT2, and this was accompanied by normalization of the glucose utilization rate. The ratio of pancreatic insulin to glucagon and volume densities of ␣ to ␤ cells were, however, not corrected. These data demonstrate that 1) reexpression of GLUT1 or GLUT2 in ␤ cells is sufficient to rescue GLUT2-null mice from lethality, 2) GLUT1 as well as GLUT2 can restore normal GSIS, 3) restoration of GSIS does not correct the abnormal composition of the endocrine pancreas. Thus, normal GSIS does not depend on transporter affinity but on the rate of uptake at stimulatory glucose concentrations.Genetic inactivation of the glucose transporter GLUT2 by homologous recombination in embryonic stem cells allowed us to generate mice deficient in the activity of this transporter (1). These GLUT2-null mice were unable to survive past the third week of life and displayed a form of diabetes mellitus characterized by hyperglycemia, relative hypoinsulinemia, and elevated glucagon levels. Their glucose tolerance was severely impaired, and as assessed in islet perifusion experiments, their pancreatic ␤ cells had completely lost the first phase while maintaining a second phase of insulin secretion. The cellular composition of the islets of Langerhans was also modified with an inversion of the ␣ to ␤ cell ratio due to an absolute increase in ␣ cell number and absolute decrease in ␤ cell numbers. As this change in cellular composition appeared only after birth, which is the time at which glucose sensitivity by pancreatic ␤ cells is being established, we postulated that the altered cellular composition of the islets was due to a defect in the secretion by ␤ cells of autocrine proliferation factors or of paracrine factors normally restricting ␣ cell proliferation.Glucose-stimulated insulin secretion (GSIS) 1 is initiated by the uptake of glucose by the glucose transporter GLUT2. Glucose is then phosphorylated by glucokinase and further metabolized through the glycolytic pathway. Activation of the mitochondrial metabolism then leads to generation of coupling factors, ATP (2, 3) and glutamate (4), which trigger the distal steps in insulin granule exocytosis. The high K m (6 mM) hexokinase IV, referred to as glucokinase, is the rate-limiting step in glucose metabolism by ␤ cells, and it therefore has a h...

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Role of the GLUT 2 Glucose Transporter in the Response of the L-type Pyruvate Kinase Gene to Glucose in Liver-derived Cells

Cited by 38 publications

References 38 publications

Glucose Regulation of Gene Transcription

Glucose Regulation of Gene Transcription

Relative contributions of L-FABP, SCP-2/SCP-x, or both to hepatic biliary phenotype of female mice

Transgenic Reexpression of GLUT1 or GLUT2 in Pancreatic β Cells Rescues GLUT2-null Mice from Early Death and Restores Normal Glucose-stimulated Insulin Secretion

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