Properties of Adaptive Hexokinase Isozymes of the Rat<sup>1</sup>

Hansen, Robert J.; Pilkis, S J; Krahl, M. E.

doi:10.1210/endo-81-6-1397

Cited by 50 publications

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“…The charge heterogeneity of glucokinase revealed by two-dimensional gel electrophoresis is reminiscent of earlier evidence for distinct electrophoretic forms of the enzyme in starch or agarose gels (7,9,21). The biochemical basis for multiple isoforms of glucokinase is unknown.…”

Section: Discussionmentioning

confidence: 70%

Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Iynedjian¹,

Möbius²,

Seitz³

et al. 1986

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

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The tissue distribution of glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was examined by protein blotting analysis. Antibodies raised against rat liver glucokinase recognized a single protein subunit with an apparent Mr of 56,500 on nitrocellulose blots of cytosol protein from liver, separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. A protein of identical electrophoretic mobility was detected by immunoblotting of cytosol protein from pancreatic islets. Hepatic glucokinase and the immunoreactive islet product bound to and were eluted from DEAE-cellulose at the same ionic strength. Glucokinase was displayed as a set of two spots with apparent pI values of 5.54 and 5.64 by immunoblotting after two-dimensional gel electrophoresis. The two isoforms appeared equally abundant in liver extract, whereas the component with a pI of 5.64 was predominant in islets. By quantitative immunoblotting, glucokinase was estimated to represent 0.1% of total cytosol protein in liver and 1/20th as much in islets. The glucokinase activity of both liver and islet cytosols was suppressed by the antibodies to hepatic glucokinase.

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Section: Discussionmentioning

confidence: 70%

Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Iynedjian¹,

Möbius²,

Seitz³

et al. 1986

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

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“…In addition, insulin increases the expression of HKII mRNA and protein, as has been demonstrated in rat (3,4) and human tissues (5)(6)(7). Interestingly, the expression and activity of HKI, the other isoform expressed in muscle and adipose tissue, is not affected by insulin, indicating a specific action of the hormone on the HKII gene (2,4,6).…”

mentioning

confidence: 52%

“…In these tissues, glucose uptake is strongly activated by insulin, which induces the translocation of the GLUT4 transporter to the plasma membrane. Simultaneously, insulin increases HKII catalytic activity (2,3), allowing an immediate metabolism of glucose in the cells. In addition, insulin increases the expression of HKII mRNA and protein, as has been demonstrated in rat (3,4) and human tissues (5)(6)(7).…”

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confidence: 99%

Sterol Regulatory Element-Binding Protein-1 Mediates the Effect of Insulin on Hexokinase II Gene Expression in Human Muscle Cells

et al. 2004

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Insulin upregulates hexokinase II (HKII) expression in skeletal muscle, and this effect is altered in type 2 diabetic patients. This study was conducted to identify the transcription factors that mediate the effect of insulin on HKII gene expression in human muscle. We have cloned the promoter region of the HKII gene and investigated its regulation in a primary culture of human skeletal muscle cells. We defined a region (

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“…Although HKI and HKII are both expressed in skeletal muscle and adipose tissue, HKII is the predominant isoform in these tissues (1). HKII catalytic activity is increased by insulin, whereas that of HKI is unaffected (3,4). L6 myotubes have been used to analyze this action of insulin.…”

mentioning

confidence: 99%

Analysis of the Signaling Pathway Involved in the Regulation of Hexokinase II Gene Transcription by Insulin

Osawa

Sutherland

Robey

et al. 1996

Journal of Biological Chemistry

117

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The hexokinases, by converting glucose to glucose 6-phosphate, help maintain the glucose concentration gradient that results in the movement of glucose into cells through the facilitative glucose transporters. Hexokinase II (HKII) is the major hexokinase isoform in skeletal muscle, heart, and adipose tissue. Insulin induces HKII gene transcription in L6 myotubes, and this, in turn, increases HKII mRNA and the rates of HKII protein synthesis and glucose phosphorylation in these cells. Inhibitors of distinct insulin signaling pathways were used to dissect the molecular mechanism by which HKII gene expression is induced by insulin in L6 myotubes. Treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), or with rapamycin, an inhibitor of the pathway from the insulin receptor to p70/p85 ribosomal S6 protein kinase (p70 s6k ), prevented the induction of HKII mRNA by insulin. In contrast, treatment with PD98059, an inhibitor of mitogen-activated protein kinase activation, had no effect on insulin-induced HKII mRNA. In addition, rapamycin blocked the insulin-induced expression of an HKII promoter-chloramphenicol acetyltransferase fusion gene transiently transfected into L6 myotubes, whereas PD98059 had no such effect. These results suggest that a phosphatidylinositol 3-kinase/p70 s6k -dependent pathway is required for regulation of HKII gene transcription by insulin and that the Ras-mitogen-activated protein kinase-dependent pathway is probably not involved.The four mammalian hexokinases (ATP:D-hexose-6-phosphotransferase, EC 2.7.1.1; designated HKI through IV) 1 are a family of closely related enzymes that convert glucose to glucose 6-phosphate (for review, see Ref. 1). This enzymatic step initiates glucose metabolism and ensures the glucose concentration gradient that results in the movement of glucose into the cell through the facilitative glucose transporters (designated GLUT1 through 5) (2). Although HKI and HKII are both expressed in skeletal muscle and adipose tissue, HKII is the predominant isoform in these tissues (1). HKII catalytic activity is increased by insulin, whereas that of HKI is unaffected (3, 4). L6 myotubes have been used to analyze this action of insulin. In these cells insulin selectively increases HKII mRNA and protein synthesis, and this is associated with an increased rate of glucose utilization (4, 5). Hyperinsulinemic clamp studies have also demonstrated that HKII mRNA is increased by insulin in human and rat skeletal muscle in vivo (6, 7).The binding of insulin to a specific cell-surface receptor results in the activation of an intrinsic receptor tyrosine kinase (for review, see Ref. 8). The activated receptor phosphorylates insulin receptor substrate-1 (IRS-1) and this phosphoprotein, through interaction with specific Src homology 2 (SH2) domaincontaining proteins, initiates divergent signaling cascades (for review, see Ref. 9). For example, the enzyme phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.67) is activated when it binds to IRS-1 (9). This leads...

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Properties of Adaptive Hexokinase Isozymes of the Rat¹

Cited by 50 publications

References 0 publications

Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Sterol Regulatory Element-Binding Protein-1 Mediates the Effect of Insulin on Hexokinase II Gene Expression in Human Muscle Cells

Analysis of the Signaling Pathway Involved in the Regulation of Hexokinase II Gene Transcription by Insulin

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Properties of Adaptive Hexokinase Isozymes of the Rat1

Cited by 50 publications

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Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets.

Sterol Regulatory Element-Binding Protein-1 Mediates the Effect of Insulin on Hexokinase II Gene Expression in Human Muscle Cells

Analysis of the Signaling Pathway Involved in the Regulation of Hexokinase II Gene Transcription by Insulin

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Properties of Adaptive Hexokinase Isozymes of the Rat¹