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• W1987966504 abstract "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 β cells. To search for such a protein in pancreatic β 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 β subunit (pβPCCase), and glutathione S-transferase pull-down assay illustrated that pβPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that pβPCCase decreased theK m value of recombinant islet glucokinase for glucose by 18% and increased V max value by 23%. We concluded that pβPCCase might be a novel activator of glucokinase in pancreatic β cells. 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 β cells. To search for such a protein in pancreatic β 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 β subunit (pβPCCase), and glutathione S-transferase pull-down assay illustrated that pβPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that pβPCCase decreased theK m value of recombinant islet glucokinase for glucose by 18% and increased V max value by 23%. We concluded that pβPCCase might be a novel activator of glucokinase in pancreatic β cells. polymerase chain reaction glutathione S-transferase glucokinase precursor of propionyl-CoA carboxylase β subunit recombinant propionyl-CoA carboxylase Glucose phosphorylation is known to be the rate-limiting step in glycolysis of pancreatic β cells (1Matschinsky F.M. Glaser B. Magnuson M.A. Diabetes. 1998; 47: 307-315Crossref PubMed Scopus (291) Google Scholar). This step is catalyzed by hexokinase through a low K m pathway and by glucokinase through a high K m pathway (2Xu L.Z. Harrison R.W. Weber I.T. Pilkis S.J. J. Biol. Chem. 1995; 270: 9939-9946Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 3Schuit F. Moens K. Heimberg H. Pipeleers D. J. Biol. Chem. 1999; 274: 32803-32809Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar). Glucokinase predominantly regulates intracellular glucose metabolism when ambient glucose concentration is increased (4Matschinsky F.M. Collins H.W. Chem. Biol. 1997; 4: 249-257Abstract Full Text PDF PubMed Scopus (16) Google Scholar), and the reduced activity of this enzyme has been reported to decrease glucose-induced insulin release (5Wang H. Iynedjian P.B. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 4372-4377Crossref PubMed Scopus (117) Google Scholar). Glucokinase is also expressed in the liver, which is another regulatory center of glucose homeostasis. Van Schaftingenet al. (6van Schaftingen E. Detheux M. da Cunha Veiga M. FASEB J. 1994; 8: 414-419Crossref PubMed Scopus (206) Google Scholar) 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 (6van Schaftingen E. Detheux M. da Cunha Veiga M. FASEB J. 1994; 8: 414-419Crossref PubMed Scopus (206) Google Scholar, 7Vandercammen A. van Schaftingen E. Eur. J. Biochem. 1990; 191: 483-489Crossref PubMed Scopus (100) Google Scholar). 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 (8Tiedge M. Steffeck H. Elsner M. Lenzen S. Diabetes. 1999; 48: 514-523Crossref PubMed Scopus (42) Google Scholar). Fructose 1-phosphate converted from fructose was reported to enhance glucokinase activity in vitro (9Malaisse W.J. Malaisse-Lagae F. Davies D.R. Vandercammen A. van Schaftingen E. Eur. J. Biochem. 1990; 190: 539-545Crossref PubMed Scopus (68) Google Scholar), and a greater increase in glucokinase activity has been reported in extracts from islets overexpressing glucokinase without an increase of glucose utilization (10Becker T.C. Noel R.J. Johnson J.H. Lynch R.M. Hirose H. Tokuyama Y. Bell G.I. Newgard C.B. J. Biol. Chem. 1996; 271: 390-394Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar). 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 β cells using the yeast two hybrid system and found a novel binding regulator for glucokinase. Rat pancreatic islet glucokinase full-length cDNA was amplified by polymerase chain reaction (PCR)1 using pancreatic β cell glucokinase-specific oligonucleotides (11Magnuson M.A. Shelton K.D. J. Biol. Chem. 1989; 264: 15936-15942Abstract Full Text PDF PubMed Google Scholar). This cDNA was subcloned into the following two types of plasmids: pBTM116, the “bait” for yeast two hybrid screen (pBTM116-GK), and pGEX4T-1 (Amersham Pharmacia Biotech) to produce glutathioneS-transferase (GST)-fused glucokinase (GST-GK). Full-length cDNA of precursor of propionyl-CoA carboxylase β subunit (pβPCCase) in pancreatic islet was also amplified from rat pancreatic islets cDNA by PCR using the oligonucleotides for rat liver pβPCCase (12Kraus J.P. Firgaira F. Novotny J. Kalousek F. Williams K.R. Williamson C. Ohura T. Rosenberg L.E. Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8049-8053Crossref PubMed Scopus (38) Google Scholar). Rat pancreatic islet glucokinase and pβPCCase were subcloned into pGEX4T-1 and transformed intoEscherichia coli strain M15. Following induction of protein expression with isopropyl thio-β-d-galactosidase, the GST fusion proteins were purified according to the manufacturer's instructions (Amersham Pharmacia Biotech) (13Inada A. Someya Y. Yamada Y. Ihara Y. Kubota A. Ban N. Watanabe R. Tsuda K. Seino Y. J. Biol. Chem. 1999; 274: 21095-21103Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar). The produced protein was dissolved in 50 mm Tris-HCl, pH 8.0. Recombinant glucokinase without GST tag (rGK) was made by thrombin cleavage according to the manufacturer's instruction. Yeast two hybrid screening was performed as described previously (14Kotake K. Ozaki N. Mizuta M. Sekiya S. Inagaki N. Seino S. J. Biol. Chem. 1997; 272: 29407-29410Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). The bait plasmid was pBTM116-GK, in which rat pancreatic β cell glucokinase was fused to the LexA DNA-binding domain. The yeast strain L40 (MATa trp1 leu2 his3 LYS2::lexA-HIS3 URA3::lexA-LacZ) was transformed with pBTM116-GK using the lithium acetate method (15Vojtek A.B. Hollenberg S.M. Cooper J.A. Cell. 1993; 74: 205-214Abstract Full Text PDF PubMed Scopus (1663) Google Scholar). Strain L40 carrying pBTM116-GK was transformed with a HIT-T15 (hamster pancreatic β cell line (16Ashcroft S.J. Hammonds P. Harrison D.E. Diabetologia. 1986; 29: 727-733Crossref PubMed Scopus (87) Google Scholar)) cell cDNA library. Approximately 1.0 × 106 transformants were screened for growth on Yc plate medium (2% glucose, 0.5% ammonium sulfate, 1% succinic acid, and 0.12% yeast nitrogen base) containing 0.5 mm3-amino-1,2,4-triazole but lacking tryptophan, histidine, uracil, and leucine. His+ colonies were then placed on paper filters and stained with 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside for β-galactosidase activity as described (15Vojtek A.B. Hollenberg S.M. Cooper J.A. Cell. 1993; 74: 205-214Abstract Full Text PDF PubMed Scopus (1663) Google Scholar). Two His+ and LacZ+ clones were obtained with this screening. The plasmids were transformed to E. coli and isolated. Pancreatic islets were isolated from male Wistar rats by collagenase digestion as described previously (17Kajikawa M. Ishida H. Fujimoto S. Mukai E. Nishimura M. Fujita J. Tsuura Y. Okamoto Y. Norman A.W. Seino Y. Endocrinology. 1999; 140: 4706-4712Crossref PubMed Google Scholar) and were then sonicated in RIPA (150 mm NaCl, 1.0% Nonidet P-40, 50 mm Tris-HCl, pH 8.0). The homogenate was centrifuged at 10,000 × g for 15 min at 4 °C, and the supernatant was collected as the islet extract. Rat liver tissue was also homogenized in RIPA, and the supernatant was collected after centrifugation at 10,000 × g for 15 min at 4 °C as liver extract. Sucrose gradient fractionation was performed for collected islets by the previously described method (18Hogebon G.H. Methods Enzymol. 1955; 1: 16-19Crossref Scopus (823) Google Scholar). Islets in the 0.25 m sucrose were homogenized in a Potter-Elvehjem homogenizer with 6 strokes of a close-fitting Teflon pestle. The mixture was centrifuged for 10 min at 600 × g. The pellet was further purified by the method of Blobel-Potter to obtain the purified nuclear fraction (19Blobel G. Van Potter R. Science. 1966; 154: 1662-1664Crossref PubMed Scopus (985) Google Scholar). The supernatant was centrifuged for 10 min at 8,000 × g. The pellet was collected as the mitochondrial fraction, and the supernatant was centrifuged for 60 min at 105,000 × g. The resultant pellet was the microsomal fraction, and the supernatant was the cytosolic fraction. Each subcellular fraction was analyzed by SDS-PAGE and Western blotting with anti-pβPCCase serum as described previously (13Inada A. Someya Y. Yamada Y. Ihara Y. Kubota A. Ban N. Watanabe R. Tsuda K. Seino Y. J. Biol. Chem. 1999; 274: 21095-21103Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar). The anti-pβPCCase serum was made from a rabbit immuned with GST-pβPCCase. GST pull-down assay was performed as described previously (13Inada A. Someya Y. Yamada Y. Ihara Y. Kubota A. Ban N. Watanabe R. Tsuda K. Seino Y. J. Biol. Chem. 1999; 274: 21095-21103Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar). Each assay contained GST fusion protein immobilized on glutathione-Sepharose beads (Amersham Pharmacia Biotech). Briefly, samples containing glucokinase (5 μg of rGK, rat pancreatic islet extract, or liver extract) were incubated with 3 μg of GST (molecular mass, 27 kDa) or 9 of μg GST-pβPCCase (molecular mass, 89 kDa) or 8 μg of GST-GK (molecular mass, 79 kDa) in binding buffer (20 mm Tris-HCl, pH 7.6, 0.1 mm EDTA, 20% glycerol, 300 mm KCl, 0.1% Nonidet P-40, 0.5 mm phenylmethylsulfonyl fluoride, 2 mm MgCl2, and 5 mm2-mercaptoethanol) for 1 h at 4 °C. 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-pβPCCase serum as described previously (13Inada A. Someya Y. Yamada Y. Ihara Y. Kubota A. Ban N. Watanabe R. Tsuda K. Seino Y. J. Biol. Chem. 1999; 274: 21095-21103Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 20Toyoda Y. Miwa I. Kamiyama M. Ogiso S. Okuda J. Nonogaki T. FEBS Lett. 1995; 359: 81-84Crossref PubMed Scopus (19) Google Scholar). Glucokinase enzyme activity was measured by a fluorometric assay according to the method reported previously (21Miwa I. Mita Y. Murata T. Okuda J. Sugiura M. Hamada Y. Chiba T. Enzyme Protein. 1995; 48: 135-142Crossref Scopus (24) Google Scholar). Glucokinase activity was measured as the fluorescence of NADPH at excitation and emission wavelengths of 340 and 450 nm, respectively. The reaction was performed in a solution consisting of 50 mm HEPES-NaOH, pH 7.4, 100 mm KCl, 8 mm MgCl2, 0.5 mm NADP, 1 mm dithiothreitol, 1 unit/ml of glucose 6-phosphate dehydrogenase, ATP at various concentrations, and 0.2 μg/ml of GST-GK supplemented with various concentrations of glucose at 37 °C for half an hour and was stopped by addition of stop solution (300 mm NaH2PO4, 0.46 mmsodium dodecylsulfate, pH 8.0). Reagent blanks were incubated in the absence of ATP and were subtracted from the total fluorescence of the corresponding complete reaction mixtures. The K m ,V max, and Hill coefficient were determined by the nonlinear least squares routine to fit the Hill equation using Sigma Plot (1Matschinsky F.M. Glaser B. Magnuson M.A. Diabetes. 1998; 47: 307-315Crossref PubMed Scopus (291) Google Scholar, 9Malaisse W.J. Malaisse-Lagae F. Davies D.R. Vandercammen A. van Schaftingen E. Eur. J. Biochem. 1990; 190: 539-545Crossref PubMed Scopus (68) Google Scholar). All data are expressed as means ± S.E., with n values being the number of experiments performed. Statistical significance was determined by paired Student'st test. The yeast two hybrid system was used to identify cDNAs in the HIT-T15 cell cDNA library encoding the regulatory protein using the bait plasmid pBTM116-GK. The resultant cDNA insert was isolated by nutritional selection and β-galactosidase activity and was shown to be 68% of the rat liver pβPCCase gene by sequence analysis. The full-length cDNA of pβPCCase was obtained from rat pancreatic islet cDNA by a PCR-based method. The specificity of the interaction between pancreatic islet glucokinase and pancreatic islet pβPCCase was tested in vitro. The GST-fused pβPCCase (GST-pβPCCase) could bind to rGK and glucokinase in cellular extracts of rat pancreatic islets and liver (Fig.1). Furthermore, the GST-fused glucokinase (GST-GK) could bind to pβPCCase in cellular extracts of rat pancreatic islets (Fig. 1 D). Western blotting was performed to confirm the subcellular localization of pβPCCase in islets. pβPCCase was shown to be present in the mitochondrial fraction and cytosolic fraction, but it was not detected in the microsomal or nuclear fractions (Fig.2). Next, the effects of GST-pβPCCase on glucokinase activity were investigated. When 25 μg/ml GST-pβPCCase was added, GST-GK activity was significantly higher than that in controls within the range of 3 to 50 mm glucose (Fig.3 A), whereas the GST tag alone did not show any effect on GST-GK activity (data not shown). GST-pβPCCase had no activity of hexokinase or glucokinase. The glucokinase inhibitor mannoheptulose at 20 mm suppressed the activity of GST-GK by 67 or 60% in the presence or absence of pβPCCase, respectively, when the activity was assayed in the presence of 10 mm glucose and 5 mm ATP. TheV max value of GST-GK for glucose was increased by about 23%, and the K m value was reduced by 18% when GST-pβPCCase was added (Table I). The Hill number was 1.8 in the presence of GST-pβPCCase, which was not significantly different from the value of 1.7 in controls (TableI). Furthermore, the K m value of GST-GK for ATP was not affected by addition of GST-pβPCCase (see Fig. 3 B and Table I). The activity of GST-GK was increased in a GST-pβPCCase concentration-dependent manner (Fig. 3 C). In the previous reports, palmitoyl-CoA has been shown to suppress glucokinase activity at higher concentrations beyond physiological ones (22Tippett P.S. Neet K.E. J. Biol. Chem. 1982; 257: 12839-12845Abstract Full Text PDF PubMed Google Scholar, 23Tippett P.S. Neet K.E. J. Biol. Chem. 1982; 257: 12846-12852Abstract Full Text PDF PubMed Google Scholar, 24Printz R.L. Magnuson M.A. Granner D.K. Annu. Rev. Nutr. 1993; 13: 463-496Crossref PubMed Scopus (170) Google Scholar). We tested the effects of pβPCCase on glucokinase activity in the presence or absence of palmitoyl-CoA and propionyl-CoA. The activating effect of GST-pβPCCase was not influenced by the presence of 3 μm palmitoyl-CoA and 3 μm propionyl-CoA (data not shown).Table IKinetic parameters of GST-GK activity in the presence or absence of GST-pβPCCaseK mV maxhK m (ATP)mmμmol/min/mgmmGST-GK6.39 ± 0.3046.89 ± 3.411.7 ± 0.30.47 ± 0.08GST-GK + GST-pβPCCase5.16 ± 0.7557.47 ± 4.341.8 ± 0.20.59 ± 0.11pValue0.0160.005NSNSh, Hill coefficient number; NS, not significant. The data are expressed as means ± S.E. K m ,V max, and h were calculated from six independent experiments, and K m (ATP) was calculated from four independent experiments. Open table in a new tab h, Hill coefficient number; NS, not significant. The data are expressed as means ± S.E. K m ,V max, and h were calculated from six independent experiments, and K m (ATP) was calculated from four independent experiments. In this study, we found that pβPCCase, which is present in the cytosolic compartment (25Browner M.F. Taroni F. Sztul E. Rosenberg L.E. J. Biol. Chem. 1989; 264: 12680-12685Abstract Full Text PDF PubMed Google Scholar, 26Moss J. Lane M.D. Adv. Enzymol. 1971; 35: 321-342PubMed Google Scholar, 27Kraus J.P. Kalousek F. Rosenberg L.E. J. Biol. Chem. 1983; 258: 7245-7248Abstract Full Text PDF PubMed Google Scholar), unexpectedly interacted with pancreatic islet glucokinase and activated its enzyme activity with increasedV max and decreased K m values for glucose. Liver and pancreatic β cells play crucial roles in glucose homeostasis, but they have distinctive functions (28Matschinsky F.M. Diabetes. 1990; 39: 647-652Crossref PubMed Google Scholar). In the liver, in response to changes in plasma glucose concentration, hepatic glucose uptake and glucose output are alternatively increased to maintain the plasma glucose concentration. Accordingly, an abrupt alteration of ambient glucose concentration might require a negative feedback loop for glucokinase activity by binding of a regulatory protein coupled to fructose 6-phospate (6van Schaftingen E. Detheux M. da Cunha Veiga M. FASEB J. 1994; 8: 414-419Crossref PubMed Scopus (206) Google Scholar, 29Siota C. Coffey J. Grimsby J. Grippo J.F. Magnuson M.A. J. Biol. Chem. 1999; 274: 37125-37130Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar). On the other hand, pancreatic β cells secrete insulin in response to increasing glucose concentration (4Matschinsky F.M. Collins H.W. Chem. Biol. 1997; 4: 249-257Abstract Full Text PDF PubMed Scopus (16) Google Scholar). A glucose-induced insulin secretion is subject to intracellular glucose metabolism, and in β cells glucose metabolism unidirectionally flows toward the direction of ATP production with the metabolic characteristic of development of a glycerol phosphate shuttle (30MacDonald M.J. J. Biol. Chem. 1981; 256: 8287-8290Abstract Full Text PDF PubMed Google Scholar), lack of fructose-bisphosphatase (31Sener A. Malaisse W.J. Diabetes Metab. 1978; 4: 127-133PubMed Google Scholar), and a low activity of lactate dehydrogenase (32Sekine N. Cirulli V. Regazzi R. Brown L.J. Gine E. Tamarit-Rodriguez J. Girotti M. Marie S. MacDonald M.J. Wollheim C.B. J. Biol. Chem. 1994; 269: 4895-4902Abstract Full Text PDF PubMed Google Scholar). However, a positive regulator of glucokinase, which has the lowest activity among all the glycolytic enzymes, had not been found in pancreatic β cells. In the present study, we demonstrated that pβPCCase increased V max of glucokinase for glucose and reduced K m . Such regulation may enable maximal enhancement of glucose metabolism in the range of physiological ambient glucose concentrations. pβPCCase is a precursor of the β subunit in propionyl-CoA carboxylase (PCCase), a biotin-dependent enzyme that is present in the matrix of mitochondria (25Browner M.F. Taroni F. Sztul E. Rosenberg L.E. J. Biol. Chem. 1989; 264: 12680-12685Abstract Full Text PDF PubMed Google Scholar, 26Moss J. Lane M.D. Adv. Enzymol. 1971; 35: 321-342PubMed Google Scholar, 27Kraus J.P. Kalousek F. Rosenberg L.E. J. Biol. Chem. 1983; 258: 7245-7248Abstract Full Text PDF PubMed Google Scholar). pβPCCase protein (61.5 kDa) is known to be synthesized on cytoplasmic polyribosomes and transferred to the mitochondria via a specific transporter. After arrival at the mitochondrial matrix, pβPCCase is processed to mature β subunit of propionyl-CoA carboxylase protein (54 kDa) by a Zn2+-dependent proteolytic component in the matrix (27Kraus J.P. Kalousek F. Rosenberg L.E. J. Biol. Chem. 1983; 258: 7245-7248Abstract Full Text PDF PubMed Google Scholar). Thus, pβPCCase could exist in the cytoplasmic compartment. The importance of the regulation of glucokinase activity by pβPCCase remains to be determined. Pancreatic β cells are continuously exposed to not only glucose but also fatty acids, which are known to affect glucose-induced insulin secretion (33Liu Y.Q. Tornheim K. Leahy J.L. J. Clin. Invest. 1998; 101: 1870-1875Crossref PubMed Scopus (53) Google Scholar, 34Unger R.H. Diabetes. 1995; 44: 863-870Crossref PubMed Google Scholar). Palmitate and oleate are strong potentiators of glucose-induced insulin release (35Hosokawa H. Corkey B.E. Leahy J.L. Diabetologia. 1997; 40: 392-397Crossref PubMed Scopus (67) Google Scholar, 36Warnotte C. Gilon P. Nenquin M. Henquin J.C. Diabetes. 1994; 43: 703-711Crossref PubMed Scopus (207) Google Scholar), and Liu et al. (33Liu Y.Q. Tornheim K. Leahy J.L. J. Clin. Invest. 1998; 101: 1870-1875Crossref PubMed Scopus (53) Google Scholar) reported that glucose utilization examined using [2H]glucose was augmented accompanied by a decrease in the level of glucose 6-phosphate in islets cultured with oleate. These findings seemed to be consistent with the hypothesis that a precursor of PCCase β subunit, which exists in the cytosolic compartment and is known to become as functional as PCCase in fatty acid metabolism in the mitochondrial matrix (36Warnotte C. Gilon P. Nenquin M. Henquin J.C. Diabetes. 1994; 43: 703-711Crossref PubMed Scopus (207) Google Scholar, 37Scholte H.R. Biochim. Biophys. Acta. 1969; 178: 137-144Crossref PubMed Scopus (60) Google Scholar), enhances the glycolytic pathway by up-regulating glucokinase activity. This hypothesis might be applicable to the glucose metabolism in the liver. In addition, pβPCCase might contribute to the localization of glucokinase by transporting the coupled enzyme in the liver and pancreatic β cells. In conclusion, pβPCCase has been shown to be a novel activator of glucokinase. Unlike the binding regulatory protein in the liver (7Vandercammen A. van Schaftingen E. Eur. J. Biochem. 1990; 191: 483-489Crossref PubMed Scopus (100) Google Scholar, 6van Schaftingen E. Detheux M. da Cunha Veiga M. FASEB J. 1994; 8: 414-419Crossref PubMed Scopus (206) Google Scholar), pβPCCase alters the K m andV max values of glucokinase for glucose, resulting in enhanced enzyme activity in islets. Because glucokinase is a rate-limiting enzyme (28Matschinsky F.M. Diabetes. 1990; 39: 647-652Crossref PubMed Google Scholar), pβPCCase may be directly involved in the regulation of glucose metabolism and glucose-induced insulin secretion in pancreatic islets. We thank Susumu Seino of Chiba University Graduate School of Medicine for arranging the yeast two hybrid screening system." @default.
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• W1987966504 title "A Novel Glucokinase Regulator in Pancreatic β Cells" @default.
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• W1987966504 cites W1479842759 @default.
• W1987966504 cites W1484067873 @default.
• W1987966504 cites W1511578599 @default.
• W1987966504 cites W1544514004 @default.
• W1987966504 cites W1552934006 @default.
• W1987966504 cites W1591547152 @default.
• W1987966504 cites W180434379 @default.
• W1987966504 cites W1846979937 @default.
• W1987966504 cites W1971595297 @default.
• W1987966504 cites W1971814438 @default.
• W1987966504 cites W1973188424 @default.
• W1987966504 cites W1992709343 @default.
• W1987966504 cites W1994686621 @default.
• W1987966504 cites W1996594730 @default.
• W1987966504 cites W2002711503 @default.
• W1987966504 cites W2003633706 @default.
• W1987966504 cites W2005063559 @default.
• W1987966504 cites W2007569151 @default.
• W1987966504 cites W2014390235 @default.
• W1987966504 cites W2019482161 @default.
• W1987966504 cites W2031796624 @default.
• W1987966504 cites W2050051162 @default.
• W1987966504 cites W2060505010 @default.
• W1987966504 cites W2066696278 @default.
• W1987966504 cites W2066931951 @default.
• W1987966504 cites W2076641946 @default.
• W1987966504 cites W2102193304 @default.
• W1987966504 cites W2103845188 @default.
• W1987966504 cites W2116828634 @default.
• W1987966504 cites W2140192657 @default.
• W1987966504 cites W2162089859 @default.
• W1987966504 cites W2162664501 @default.
• W1987966504 cites W2201784617 @default.
• W1987966504 cites W4206226084 @default.
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