Abstract
Glucokinase (EC 2.7.1.2) is the signal-recognition enzyme in pancreatic B-cells for initiation of glucose-induced insulin secretion. We show here that both the glucokinase and glucose-transporter GLUT-2 genes are regulated physiologically. Fasting decreased B-cell glucokinase and glucose-transporter GLUT-2 mRNA in pancreatic B-cells as well as in liver, whereas refeeding induced expression of both genes. In pancreatic B-cells a approximately 4.4 kb glucokinase-related mRNA was detectable, in addition to the 2.8 kb form. This approximately 4.4 kb glucokinase transcript was drastically decreased during refeeding. The 2.8 kb mRNA, which is typical for pancreatic B-cells, was accompanied after refeeding by a 2.4 kb mRNA species typical for liver glucokinase. Starvation primarily decreased the 2.8 kb pancreatic B-cell glucokinase mRNA species. The concordant regulation of both genes may represent the basis for the physiological regulation of glucose-induced insulin secretion at a transcriptional level.
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- Bedoya F. J., Matschinsky F. M., Shimizu T., O'Neil J. J., Appel M. C. Differential regulation of glucokinase activity in pancreatic islets and liver of the rat. J Biol Chem. 1986 Aug 15;261(23):10760–10764. [PubMed] [Google Scholar]
- Boam D. S., Clark A. R., Docherty K. Positive and negative regulation of the human insulin gene by multiple trans-acting factors. J Biol Chem. 1990 May 15;265(14):8285–8296. [PubMed] [Google Scholar]
- Burch P. T., Trus M. D., Berner D. K., Leontire A., Zawalich K. C., Matschinsky F. M. Adaptation of glycolytic enzymes: glucose use and insulin release in rat pancreatic islets during fasting and refeeding. Diabetes. 1981 Nov;30(11):923–928. doi: 10.2337/diab.30.11.923. [DOI] [PubMed] [Google Scholar]
- Chen L., Alam T., Johnson J. H., Hughes S., Newgard C. B., Unger R. H. Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4088–4092. doi: 10.1073/pnas.87.11.4088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- French S. W. Effect of chronic ethanol ingestion on liver enzyme changes induced by thiamine, riboflavin, pyridoxine, or choline deficiency. J Nutr. 1966 Mar;88(3):291–302. doi: 10.1093/jn/88.3.291. [DOI] [PubMed] [Google Scholar]
- Fölsch U. R., Fischer H., Söling H. D., Creutzfeldt W. Effects of gastrointestinal hormones and carbamylcholine on cAMP accumulation in isolated pancreatic duct fragments from the rat. Digestion. 1980;20(4):277–292. doi: 10.1159/000198449. [DOI] [PubMed] [Google Scholar]
- Fölsch U. R., Fussek M., Ebert R., Creutzfeldt W. Endocrine pancreatic function during atrophy of the exocrine gland. Pancreas. 1988;3(5):536–542. doi: 10.1097/00006676-198810000-00005. [DOI] [PubMed] [Google Scholar]
- Hughes S. D., Quaade C., Milburn J. L., Cassidy L., Newgard C. B. Expression of normal and novel glucokinase mRNAs in anterior pituitary and islet cells. J Biol Chem. 1991 Mar 5;266(7):4521–4530. [PubMed] [Google Scholar]
- Iynedjian P. B., Pilot P. R., Nouspikel T., Milburn J. L., Quaade C., Hughes S., Ucla C., Newgard C. B. Differential expression and regulation of the glucokinase gene in liver and islets of Langerhans. Proc Natl Acad Sci U S A. 1989 Oct;86(20):7838–7842. doi: 10.1073/pnas.86.20.7838. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iynedjian P. B., Ucla C., Mach B. Molecular cloning of glucokinase cDNA. Developmental and dietary regulation of glucokinase mRNA in rat liver. J Biol Chem. 1987 May 5;262(13):6032–6038. [PubMed] [Google Scholar]
- Johnson J. H., Newgard C. B., Milburn J. L., Lodish H. F., Thorens B. The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence. J Biol Chem. 1990 Apr 25;265(12):6548–6551. [PubMed] [Google Scholar]
- Lenzen S. Hexose recognition mechanisms in pancreatic B-cells. Biochem Soc Trans. 1990 Feb;18(1):105–107. doi: 10.1042/bst0180105. [DOI] [PubMed] [Google Scholar]
- Lenzen S., Panten U. Signal recognition by pancreatic B-cells. Biochem Pharmacol. 1988 Feb 1;37(3):371–378. doi: 10.1016/0006-2952(88)90201-8. [DOI] [PubMed] [Google Scholar]
- Lenzen S., Tiedge M., Flatt P. R., Bailey C. J., Panten U. Defective regulation of glucokinase in rat pancreatic islet cell tumours. Acta Endocrinol (Copenh) 1987 Aug;115(4):514–520. doi: 10.1530/acta.0.1150514. [DOI] [PubMed] [Google Scholar]
- Magnuson M. A., Shelton K. D. An alternate promoter in the glucokinase gene is active in the pancreatic beta cell. J Biol Chem. 1989 Sep 25;264(27):15936–15942. [PubMed] [Google Scholar]
- Malaisse W. J., Sener A., Levy J. The stimulus-secretion coupling of glucose-induced insulin release. Fasting-induced adaptation of key glycolytic enzymes in isolated islets. J Biol Chem. 1976 Mar 25;251(6):1731–1737. [PubMed] [Google Scholar]
- Meglasson M. D., Matschinsky F. M. Pancreatic islet glucose metabolism and regulation of insulin secretion. Diabetes Metab Rev. 1986;2(3-4):163–214. doi: 10.1002/dmr.5610020301. [DOI] [PubMed] [Google Scholar]
- Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Orci L., Ravazzola M., Baetens D., Inman L., Amherdt M., Peterson R. G., Newgard C. B., Johnson J. H., Unger R. H. Evidence that down-regulation of beta-cell glucose transporters in non-insulin-dependent diabetes may be the cause of diabetic hyperglycemia. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9953–9957. doi: 10.1073/pnas.87.24.9953. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Permutt M. A., Koranyi L., Keller K., Lacy P. E., Scharp D. W., Mueckler M. Cloning and functional expression of a human pancreatic islet glucose-transporter cDNA. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8688–8692. doi: 10.1073/pnas.86.22.8688. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thorens B., Flier J. S., Lodish H. F., Kahn B. B. Differential regulation of two glucose transporters in rat liver by fasting and refeeding and by diabetes and insulin treatment. Diabetes. 1990 Jun;39(6):712–719. doi: 10.2337/diab.39.6.712. [DOI] [PubMed] [Google Scholar]
- Thorens B., Sarkar H. K., Kaback H. R., Lodish H. F. Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells. Cell. 1988 Oct 21;55(2):281–290. doi: 10.1016/0092-8674(88)90051-7. [DOI] [PubMed] [Google Scholar]
- Unger R. H. Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science. 1991 Mar 8;251(4998):1200–1205. doi: 10.1126/science.2006409. [DOI] [PubMed] [Google Scholar]
- Weaver C., Sorenson R. L., Kobienia B. Nonenzymatic isolation and culture of adult islets from atrophic pancreata of copper-deficient rats: a morphologic analysis. In Vitro Cell Dev Biol. 1988 Feb;24(2):108–116. doi: 10.1007/BF02623887. [DOI] [PubMed] [Google Scholar]
- Weinhouse S. Regulation of glucokinase in liver. Curr Top Cell Regul. 1976;11:1–50. [PubMed] [Google Scholar]