Hexokinase and glucokinase distribution in the liver lobule.

Trus, Michael D; Zawalich, Kathleen C.; Gaynor, D; Matschinsky, Franz M.

doi:10.1177/28.6.7391551

Cited by 55 publications

(23 citation statements)

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“…Conversely, there is a high activity of key glycolytic enzymes in the perivenous zone: glucokinase and pyruvate kinaseL (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Our results indicate a correlation between expression of the erythroid/ brain GT and cells using glucose as a carbon source via glycolysis.…”

Section: Discussionsupporting

confidence: 53%

Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

Tal¹,

Schneider²,

Thorens³

et al. 1990

J. Clin. Invest.

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The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a threeto fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepatic venules. Starvation-dependent expression of the erythroid/ brain GT on the plasma membrane of these additional hepatocytes is lost within 3 h of glucose refeeding; however, by immunoblotting we show that the protein is still present. Its loss from the surface is possibly explained by internalization. (J.Clin. Invest. 1990. 86:986-992.) Key words: starvation * liver glucose transporter * glucose refeeding * regulation and internalization Introduction The liver plays a key role in glucose homeostasis. Of the blood entering the liver, 75% comes from the digestive system via the portal vein and 25% from the hepatic artery. During passage of blood through the liver, glucose in excess of 5 mM (after a meal) is removed; it is either stored as glycogen or catabolized by glycolysis. Between meals and during starvation, when blood glucose is lower then 5 mM, hepatic glycogen degradation and gluconeogenesis result in release of glucose into the blood. Thus, constant blood glucose concentration is maintained by the parenchymal cells (hepatocytes).

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Section: Discussionsupporting

confidence: 53%

Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

Tal¹,

Schneider²,

Thorens³

et al. 1990

J. Clin. Invest.

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“…No specific reaction products were observed in sections ofbrain, kidney, adipose, and muscle using the, ABC peroxidase method (results not shown). In addition, both antibodies detected a perivenous distribution of immunoreactivity in the liver parenchyma (data not shown), typical of GK (16,17).…”

Section: Resultsmentioning

confidence: 76%

Heterogeneous expression of glucokinase among pancreatic beta cells.

Jetton

Magnuson

1992

Proc. Natl. Acad. Sci. U.S.A.

109

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The cellular location of glucokinase (GK), a key component of the glucose-sensing mechanism of the pancreatic islet, was determined using immunocytochemical techniques. In rat islets, GK imm noreactivity was detected only in (3 cells with no immunoreactivit detected in a, 8, or pancreatic polypeptide-containing (PP) cells. However, within various (3 cells, GK immunoreactivity varied considerably. Most (3 cells displayed relatively low levels ofcytoplasmic immunoreactivity whereas other (3 cells stained intensely for this enzyme. Colocalization studies of GK and GLUT2, the hih K. glucose transporter of( cells, confirmed that these proteins are located in different subcellular domains of (3 cells. The lack of GK immunoreactivity in glucagon-and somatostatin-secreting cells in islets suggests that these cells are not directly responsive to glucose or utilize a fundamentally different mechanism for sensing glucose fluctuations. Moreover, the differential expression of GK among pancreatic (3 cells suggests that glucose phosphorylation is the probable enzymatic control point for the functional diversity of these cells.Glucokinase (GK) has been identified only in liver and the pancreatic islets of Langerhans where distinct isoforms are generated due to tissue-specific alternate RNA splicing ofthe GK gene product (1,2). In islet (3 cells, GK plays a key role in the regulation of insulin secretion. This functionally unique hexokinase catalyzes the high Km conversion of glucose to glucose 6-phosphate, the rate-limiting step in glucose utilization by pancreatic (3 cells (3), thus translating fluctuations in intracellular glucose levels to changes in the rate of glycolysis. Increases in the rate of glucose usage by (3 cells, mediated by GK, are followed by changes in K' and Ca2" channel conductance, a resultant increase in intracellular [Ca2+], and then an increase in the rate of insulin secretion (4-6). The pivotal role of GK in regulating glucose metabolism of the P cell has been established by numerous biochemical studies leading the enzyme to be termed the (-cell "glucose sensor" (3).Both glucagon and somatostatin secretion by the islet a and 8 cells, respectively, are influenced by plasma glucose levels (7). Whether these cells are able to directly sense changes in glucose concentration or, instead, may respond to paracrine factors emanating from ( cells has not been resolved. Since the only defined mechanism by which a cell can directly respond to fluxes in glucose concentrations in the physiologic range involves the expression of GK (3), we sought to determine whether a and 6 cells of the islet express this enzyme. A previous study measuring GK activity in streptozoticin-treated rats suggested that enzyme activity was not restricted to the (3 cell but also was present in the glucagonand/or somatostatin-secreting cells of the islet (8 MATERIALS AND METHODSAntibody Generation. Two antibodies directed against GK were used for the immunodetection of this enzyme in normoglycemic rat pancreatic islets. An anti-gl...

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“…The periportal hepatocytes are rich in the glucose-forming enzymes glucose-6-phosphatase [5, 61, fructose-l,6-bisphosphatase [7, 81, phosphoenolpyruvate carboxykinase (PCK) [9 -1 I], alanine aminotransferase [I21 and tyrosine aminotransferase [12]. The perivenous cells are rich in the glucose-utilizing enzymes glucokinase [7,13,141 and pyruvate kinase L [9,15]. Evidence that the periportal cells are predominantly gluconeogenic and the perivenous cells glycolytic comes from studies in vivo and in vitro: zonal flux differences were calculated from enzyme and metabolite distributions measured in vivo [16].…”

mentioning

confidence: 99%

Modulation by oxygen of the glucagon‐dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures

Hellkamp

Christ

Bastian

et al. 1991

European Journal of Biochemistry

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In liver phosphoenolpyruvate carboxykinase (PCK) activity, protein and mRNA are localized predominantly in the periportal zone. The activation of the PCK gene by glucagon was studied in primary rat hepatocyte cultures under physiological arterial and venous oxygen tensions [16% and 8% (by vol.)]. PCK gene expression was monitored on the level of transcription, mRNA abundance and enzyme activity as well as enzyme synthesis and degradation.1. Transcription of the PCK gene was increased by 10 nM glucagon maximally after 0.5 h; it reached nearly basal levels again after 2 h. The increase in transcription was 45% lower under 8% oxygen than under 16% oxygen.2. PCK mRNA was maximally increased after 2 h under 16% oxygen and after 4 h under 8% oxygen; it subsequently declined to twice the basal values after 8 h. The maximal increase after 2 h was 50% lower under 8 % oxygen than under 16% oxygen.3. PCK enzyme activity was maximally increased after 4 -6 h. The maximal enhancement after 4 h was 50% lower under 8% oxygen than under 16% oxygen.4. The increase in PCK enzyme activity was due to an enhanced synthesis rate of PCK protein. The rate increase after 3 h was 35% lower under 8% oxygen than under 16% oxygen.5. The degradation of PCK protein was equal under both oxygen tensions.The results show that in cultured rat hepatocytes the induction of PCK gene expression is modulated by physiological concentrations of oxygen. The modulation occurred at the level of gene transcription, mRNA abundance, enzyme protein synthesis and enzyme activity. The periportal to perivenous oxygen gradient could be the major factor responsible for the predominant expression of the PCK gene in the periportal zone.Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their content of enzymes and subcellular structures (reviews [1][2][3][4]). The periportal hepatocytes are rich in the glucose-forming enzymes glucose-6-phosphatase [5, 61, fructose-l,6-bisphosphatase [7, 81, phosphoenolpyruvate carboxykinase (PCK) [9 -1 I], alanine aminotransferase [I21 and tyrosine aminotransferase [12]. The perivenous cells are rich in the glucose-utilizing enzymes glucokinase [7,13,141 and pyruvate kinase L [9,15]. Evidence that the periportal cells are predominantly gluconeogenic and the perivenous cells glycolytic comes from studies in vivo and in vitro: zonal flux differences were calculated from enzyme and metabolite distributions measured in vivo [16]. They were observed in periportal-like and perivenous-like hepatocytes in

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Hexokinase and glucokinase distribution in the liver lobule.

Cited by 55 publications

References 0 publications

Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose.

Heterogeneous expression of glucokinase among pancreatic beta cells.

Modulation by oxygen of the glucagon‐dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures

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