Glucokinase gene

Figure 37-14. Alternative promoter use in the liver and pancreatic B cell glucokinase genes. Differential regulation of the glucokinase GK) gene is accomplished by the use of tissue-specific promoters. The B cell GK gene promoter and exon 1B are located about 30 kbp upstream from the liver promoter and exon 1L. Each promoter has a unique structure and is regulated differently. Exons 2-10 are identical in the two genes, and the GK proteins encoded by the liver and B cell mRNAs have identical kinetic properties.

Roncero, I., Alvarez, E., Chowen, J. A. et al. Expression of glucose transporter isoform GLUT-2 and glucokinase genes in human brain. J. Neurochem. 88 1203-1210, 2004. 

Chauhan J and Dakshinamurti K (1991) Transcriptional regulation of the glucokinase gene by biotin in starved rats. Journal of Biological Chemistry 266,10035-8. 

Hoppner, W., and Sieiz, H -J. (1989) Effect of thyroid hormones on glucokinase gene transcription in rat liver, f, Biol, Client- 264, 20643-20647-Kaptein, E. M. (1996). Thyroid hormone metabolism and thyroid diseases in chronic renal failure. Ernlocr. Rev. 17, 45-65... 

Lynch RM, Tompkins LS, Brooks HL, Dunn-Meynell AA, Levin BE. 2000. Localization of glucokinase gene expression in the rat brain. Diabetes 49 693-700. 

Type 1 DM idiopathic is a nonimmune form of diabetes frequently seen in minorities with intermittent insulin requirements. The prevalence of type 1 DM has been increasing over the last one hundred years. Maturity onset diabetes of youth (MODY), which has an identifiable genetic defect in the glucokinase gene, and endocrine disorders such as acromegaly and Cushing s syndrome, can be secondary causes of DM. These unusual etiologies, however, only account for 1% to 2% of the total cases of type 2 DM. See the section on other forms of diabetes mellitus later in this chapter for further discussion. 

Roth U, Curth K, Unterman TG, Kietzmann T. The transcription factors H3E-1 and HNF-4 and the coactivator p300 are involved in insulin-regulated glucokinase gene expression via the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 2004 279 2623-2631. 

Pioneering studies by Dakshinamurti and co-workers suggested a role for biotin in the regulation of the glucokinase gene (Dakshinamurti and Cheah-Tan 1968). Subsequently, it was shown that biotin affects gene regulation by... 

Froguel and co-workers (1993) reported studies of the glucokinase gene in a number of families affected by MOD56 and also in unaffected families. They published a list of 16 variants of the glucokinase gene, shown in Table 2.3. All their patients with MODY had an abnormality of the gene. 

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