Changes in subcellular and zonal distribution of glucokinase in rat liver during postnatal development

Toyoda, Yusuke; Miwa, Ichitomo; Kamiya, Masahiro; S, Ogiso; Okuda, Jun; Nonogaki, Tsunemasa

doi:10.1016/0014-5793(94)01452-7

Cited by 14 publications

(15 citation statements)

References 17 publications

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“…4 (which maps GK activity on a point-by point basis along the lobular radius), that in control livers the immediate perivenous cells contained a large concentration of GK (substantially greater than in the immediate periportal cells, and much greater than in the cells of the midzone of the lobule where the activity of GK is in any case probably overestimated due to difficulty of curve-fitting to the abrupt changes in this region). This distribution has similarities with that shown by immunochemical methods to be established by 30 d after birth in normal rats (19). In control livers, there are ‫ف‬ 15 hepatocytes along the lobular radius.…”

Section: Hepatic Glucose Production In Nondigitonized Perfused Liverssupporting

confidence: 78%

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Burns¹,

Desai²,

Cohen³

et al. 1997

J. Clin. Invest.

218

162

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Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-hstarved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region. (

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Section: Hepatic Glucose Production In Nondigitonized Perfused Liverssupporting

confidence: 78%

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Burns¹,

Desai²,

Cohen³

et al. 1997

J. Clin. Invest.

218

162

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“…GK and GKRP are not expressed homogenously in all the parenchymal cells in the liver. GK is expressed from periportal to perivenous areas in an increasing gradient in normal (38,61) and ZDF rats (data not shown). Even in perivenous areas, the intensities of immunofluorescence of GK and GKRP vary among hepatocytes (data not shown).…”

Section: Methodsmentioning

confidence: 91%

“…Studies using cultured hepatocytes have repeatedly shown that glucose per se is a potent stimulator of GK translocation (2,13,60,62), whereas the results regarding the effect of insulin are controversial (3,13,61). We recently reported (15) that increases in plasma glucose and/or insulin levels within the physiological range cause rapid GK translocation in conscious normal rats.…”

mentioning

confidence: 99%

Defect in glucokinase translocation in Zucker diabetic fatty rats

Fujimoto¹,

Donahue²,

Shiota³

2004

American Journal of Physiology-Endocrinology and Metabolism

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Hepatic glucose fluxes and intracellular movement of glucokinase (GK) in response to increased plasma glucose and insulin were examined in 10-wk-old, 6-h-fasted, conscious Zucker diabetic fatty (ZDF) rats and lean littermates. Under basal conditions, plasma glucose (mmol/l) and glucose turnover rate (GTR; mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) were slightly higher in ZDF (8.4 Ϯ 0.3 and 53 Ϯ 7, respectively) than in lean rats (6.2 Ϯ 0.2 and 45 Ϯ 4, respectively), whereas plasma insulin (pmol/l) was higher in ZDF (1,800 Ϯ 350) than in lean rats (150 Ϯ 14). ) were higher in ZDF (35 Ϯ 5, 87 Ϯ 16, and 33 Ϯ 10, respectively) compared with lean rats (18 Ϯ 3, 56 Ϯ 6, and 11 Ϯ 2, respectively). [3 H]glucose incorporation into glycogen (mol glucose/g liver) was similar in lean (1.0 Ϯ 0.7) and ZDF (1.6 Ϯ 0.8) rats. GK was predominantly located in the nucleus in both rats. With elevated plasma glucose and insulin, GTR (mol ⅐ kg3 H]G (%), and [ 3 H]glucose incorporation into glycogen (mol glucose/g liver) were markedly higher in lean (191 Ϯ 22, 62 Ϯ 3, and 5.0 Ϯ 1.4, respectively) but similar in ZDF rats (100 Ϯ 6, 37 Ϯ 3, and 1.4 Ϯ 0.4, respectively) compared with basal conditions. GK translocation from the nucleus to the cytoplasm occurred in lean but not in ZDF rats. The unresponsiveness of hepatic glucose flux to the rise in plasma glucose and insulin seen in prediabetic ZDF rats was associated with impaired GK translocation.liver; glucose flux; insulin; hyperglycemia PATIENTS WITH TYPE 2 DIABETES exhibit preprandial hyperglycemia and excessive postprandial hyperglycemia. The preprandial hyperglycemia is due to impaired suppression of endogenous glucose production in response to increased plasma glucose and/or insulin as well as impaired glucose uptake in peripheral tissues (19,41,42). In addition to these impairments, a defect of splanchnic glucose uptake has been reported to contribute to the occurrence of excessive postprandial hyperglycemia (9, 10, 24). Changes in plasma glucose and insulin are major factors regulating net hepatic glucose flux (8, 52). The flux is the balance between the rate of glucose phosphorylation catalyzed by glucokinase (GK) and the rate of dephosphorylation of glucose 6-phosphate (G-6-P) catalyzed by glucose-6-phosphatase (G-6-Pase). In studies using normal rats, glucose-induced suppression of net hepatic glucose production (HGP) was associated with increased glucose phosphorylation (53), and intact GK activity was required for the normal suppression of HGP by hyperglycemia (7). Basu et al. (9,10) showed that lower net splanchnic glucose uptake during a hyperglycemic hyperinsulinemic clamp in type 2 diabetic subjects was associated with a proportionate decrease in both the flux through the uridine 5Ј-diphosphate (UDP)-glucose pool and the percentage of contribution of extracellular glucose to glycogen synthesis by the direct pathway (glucose 3 G-6-P 3 G-1-P 3 UDP-glucose 3 glycogen) compared with nondiabetic subjects. Mevorach et al. (42) reported a lack of increasing glucose cycling (GC) in the presence of u...

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Section: Preparation Of Rat Pancreatic Islet and Livermentioning

confidence: 99%

“…After incubation, the beads were washed five times with binding buffer (10-fold volume of beads) and resuspended in elution buffer (binding buffer containing 10 mM reduced glutathione). The bound proteins were resolved by 10% SDS-PAGE and visualized by Western blotting with rabbit anti-glucokinase antibody or anti-p␤PCCase serum as described previously (13,20).Assay for Glucokinase Activity-Glucokinase enzyme activity was measured by a fluorometric assay according to the method reported previously (21). Glucokinase activity was measured as the fluorescence of NADPH at excitation and emission wavelengths of 340 and 450 nm, respectively.…”

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confidence: 99%

A Novel Glucokinase Regulator in Pancreatic β Cells

Shiraishi

Yamada

Tsuura

et al. 2001

Journal of Biological Chemistry

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A glucokinase regulatory protein has been reported to exist in the liver, which suppresses enzyme activity in a complex with fructose 6-phosphate, whereas no corresponding protein has been found in pancreatic ␤ cells.To search for such a protein in pancreatic ␤ cells, we screened for a cDNA library of the HIT-T15 cell line with the cDNA of glucokinase from rat islet by the yeast two hybrid system. We detected a cDNA encoding the precursor of propionyl-CoA carboxylase ␤ subunit (p␤PCCase), and glutathione S-transferase pull-down assay illustrated that p␤PCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that p␤PCCase decreased the K m value of recombinant islet glucokinase for glucose by 18% and increased V max value by 23%. We concluded that p␤PCCase might be a novel activator of glucokinase in pancreatic ␤ cells.Glucose phosphorylation is known to be the rate-limiting step in glycolysis of pancreatic ␤ cells (1). This step is catalyzed by hexokinase through a low K m pathway and by glucokinase through a high K m pathway (2, 3). Glucokinase predominantly regulates intracellular glucose metabolism when ambient glucose concentration is increased (4), and the reduced activity of this enzyme has been reported to decrease glucose-induced insulin release (5). Glucokinase is also expressed in the liver, which is another regulatory center of glucose homeostasis. Van Schaftingen et al. (6) have reported that the rat liver contains a regulatory protein that binds to glucokinase, and the activity of glucokinase coupled to this protein is thought to be mediated by competitive binding of fructose 6-phosphate and fructose 1-phosphate in the liver (6, 7). Thus, this feedback regulation may affect the balance of glycolysis and gluconeogenesis. There have also been attempts to find a corresponding protein in pancreatic islets (8). Fructose 1-phosphate converted from fructose was reported to enhance glucokinase activity in vitro (9), and a greater increase in glucokinase activity has been reported in extracts from islets overexpressing glucokinase without an increase of glucose utilization (10). These reports suggested the existence of a factor capable of regulating glucokinase activity or its affinity for glucose under physiological intracellular conditions, although as yet, no direct evidence for such a molecule has been reported. To clarify whether a glucokinase regulatory protein is present in pancreatic islets, we screened for a cDNA library of the HIT-T15 cell line with the cDNA of glucokinase from rat pancreatic ␤ cells using the yeast two hybrid system and found a novel binding regulator for glucokinase. EXPERIMENTAL PROCEDUREScDNA Cloning-Rat pancreatic islet glucokinase full-length cDNA was amplified by polymerase chain reaction (PCR) 1 using pancreatic ␤ cell glucokinase-specific oligonucleotides (11). This cDNA was subcloned into the following two types of plasmids: pBTM116, the "bait" for yeast two hybrid screen (pBTM116-GK), a...

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Changes in subcellular and zonal distribution of glucokinase in rat liver during postnatal development

Cited by 14 publications

References 17 publications

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Defect in glucokinase translocation in Zucker diabetic fatty rats

A Novel Glucokinase Regulator in Pancreatic β Cells

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