Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding

Helena C. Murphy, Gemma Regan, Irina G. Bogdarina, Adrian J.L. Clark, Richard A. Iles, Robert D. Cohen, Graham A. Hitman, Colin L. Berry, Zoe Coade, Clive J. Petry, Shamus P. Burns

Research output: Contribution to journal › Article

6 Citations (Scopus)

Abstract

Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)-an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0-8 mmol/l) in control but not MLP liver, indicating that GK is fluxgenerating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.
Original languageEnglish
Pages (from-to)1326-1332
Number of pages7
JournalDiabetes
Volume52
Issue number6
DOIs
Publication statusPublished - Jun 2003
Externally publishedYes

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Fetal Development
Glucokinase
Glucose
Liver
Gluconeogenesis
Glycogen
Type 2 Diabetes Mellitus
Glucose Intolerance
Cell Nucleus Active Transport
Hepatocytes
Fasting
Down-Regulation
Pregnancy

Cite this

Murphy, Helena C. ; Regan, Gemma ; Bogdarina, Irina G. ; Clark, Adrian J.L. ; Iles, Richard A. ; Cohen, Robert D. ; Hitman, Graham A. ; Berry, Colin L. ; Coade, Zoe ; Petry, Clive J. ; Burns, Shamus P. / Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding. In: Diabetes. 2003 ; Vol. 52, No. 6. pp. 1326-1332.
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abstract = "Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)-an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0-8 mmol/l) in control but not MLP liver, indicating that GK is fluxgenerating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.",
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Murphy, HC, Regan, G, Bogdarina, IG, Clark, AJL, Iles, RA, Cohen, RD, Hitman, GA, Berry, CL, Coade, Z, Petry, CJ & Burns, SP 2003, 'Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding', Diabetes, vol. 52, no. 6, pp. 1326-1332. https://doi.org/10.2337/diabetes.52.6.1326

Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding. / Murphy, Helena C.; Regan, Gemma; Bogdarina, Irina G.; Clark, Adrian J.L.; Iles, Richard A.; Cohen, Robert D.; Hitman, Graham A.; Berry, Colin L.; Coade, Zoe; Petry, Clive J.; Burns, Shamus P.

In: Diabetes, Vol. 52, No. 6, 06.2003, p. 1326-1332.

Research output: Contribution to journal › Article

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AU - Murphy, Helena C.

AU - Regan, Gemma

AU - Bogdarina, Irina G.

AU - Clark, Adrian J.L.

AU - Iles, Richard A.

AU - Cohen, Robert D.

AU - Hitman, Graham A.

AU - Berry, Colin L.

AU - Coade, Zoe

AU - Petry, Clive J.

AU - Burns, Shamus P.

PY - 2003/6

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N2 - Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)-an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0-8 mmol/l) in control but not MLP liver, indicating that GK is fluxgenerating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.

AB - Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restricted during gestation (MLP rats)-an environmental model of fetal programming of adult glucose intolerance exhibiting diminished perivenous glucokinase (GK) activity. We now show that perivenous glucose uptake rises with increasing glucose concentration (0-8 mmol/l) in control but not MLP liver, indicating that GK is fluxgenerating. The data demonstrate that acute control of hepatic glucose output is principally achieved by increasing perivenous glucose uptake, with rising glucose concentration during refeeding, rather than by downregulation of gluconeogenesis, which occurs in different hepatocytes. Consistent with these observations, glycogen synthesis in vivo commenced in the perivenous cells during refeeding, MLP livers accumulating less glycogen than controls. GK gene transcription was unchanged in MLP liver, the data supporting a recently proposed posttranscriptional model of GK regulation involving nuclear-cytoplasmic transport. The results are pertinent to impaired regulation of hepatic glucose output in type 2 diabetes, which could arise from diminished GK-mediated glucose uptake rather than increased gluconeogenesis.

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Murphy HC, Regan G, Bogdarina IG, Clark AJL, Iles RA, Cohen RD et al. Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding. Diabetes. 2003 Jun;52(6):1326-1332. https://doi.org/10.2337/diabetes.52.6.1326

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