High impact information on Hk2

• In differentiated adipocytes Foxa-2 expression leads to induction of gene expression involved in glucose and fat metabolism, including glucose transporter-4, hexokinase-2, muscle-pyruvate kinase, hormone-sensitive lipase, and uncoupling proteins-2 and -3 [1].
• Consistent with this hypothesis, expression of the three genes involved in glucose uptake and glycolytic commitment, those for Glut1, hexokinase 2, and phosphofructokinase 1, was found to rapidly decline to nearly undetectable levels following growth factor withdrawal [2].
• Hexokinase (HK) in the CFU-E contained mainly a double-banded type I isozyme, in addition to a minor amount of HK II [3].
• However, when glucose phosphorylation capacity is increased by HK II overexpression, GLUT4 availability becomes a marked limitation to exercise-stimulated MGU [4].
• Thus, C57BL/6J mice with hexokinase II (HKII) overexpression (HK(Tg)), a GLUT4 partial knock-out (G4(+/-)), or both (HK(Tg) + G4(+/-)) and wild-type (WT) littermates were implanted with carotid artery and jugular vein catheters for sampling and infusions at 4 months of age [4].

Biological context of Hk2

• Using these MLC-GLUT4 transgenic mice as a model, we investigated the effects of increased glucose flux on hexokinase II (HK II) gene expression in skeletal muscle [5].
• Mice homozygous for hexokinase II deficiency (HKII(-/-)) died at approximately 7.5 days post-fertilization, indicating that hexokinase II is vital for mouse embryogenesis after implantation and before organogenesis [6].
• As a first step towards elucidation of the physiological role of HKII in insulin resistance and type 2 diabetes using mouse knock-out models, we determined the genomic structure, sequence of the cDNA and of 4.8 kb of the 5' regulatory region, and tissue-specific expression of the mouse HKII gene [7].
• The transcription initiation and polyadenylation sites for the mouse HKII mRNA were similar to those of the rat and human genes [7].

Anatomical context of Hk2

• However, the alpha2-KO did not reduce training-induced increases in HKII, GLUT4, COX-1, HAD, or CS protein in WG, suggesting that AMPKalpha2 may not be essential for metabolic adaptations of skeletal muscles to exercise training [8].
• Under conditions where blood glucose levels were normal and insulin levels decreased by 36%, HK II mRNA level was reduced in non-GLUT4-overexpressing tissues (i.e. heart and adipose tissue) of 2-4-month-old male MLC-GLUT4 transgenic mice [5].
• However, the uniform requirement for classic MAPK pathway activation distinguishes HKII regulation in mesangial cells from that observed in muscle [9].
• Separate experiments demonstrated a reduction of HKII protein abundance by 61% in epididymal fat (P < 0.001, n = 12 for each experimental condition) and by 71% in the quadriceps muscles (P < 0.001, n = 6 for each experimental condition) [10].

Associations of Hk2 with chemical compounds

• The regulation of hexokinase-2 (HKII) was investigated as a marker of the glucose metabolic pathway and that of FAS was investigated as a marker of the lipogenic pathway [11].
• Exercise training increased GLUT4, HKII, COX-1, CS, and HAD protein in WG, but the alpha2-KO did not affect training-induced increases [8].
• Both stimuli were associated with increased HK activity, selectively increased HKII isoform expression, and increased Glc metabolism via both the glycolytic-tricarboxylic acid cycle route and the pentose phosphate pathway [9].
• Changes in HK activity were associated with both increased Glc metabolism and selective increases in HKII isoform abundance [12].
• In comparison with untreated diabetic mice, there was an increase in the abundance of HKII protein in epididymal fat of animals treated with pioglitazone (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)[10]

Other interactions of Hk2

• Regulation of SREBP-1 expression and transcriptional action on HKII and FAS genes during fasting and refeeding in rat tissues [11].
• In WG, AICAR treatment increased HKII, GLUT4, cytochrome c, COX-1, and CS, and the alpha2-KO abolished the AICAR-induced increases, whereas no AICAR responses were observed in RG [8].
• We conclude that IL-1 cytokines can regulate cellular Glc phosphorylating capacity via an IL-1 receptor-, Ras-, and classic MAPK pathway-mediated increase in HKII abundance [12].
• The levels of hormone sensitive lipase and hexokinase 2 transcripts were not significantly different in both groups [13].
• Surprisingly, even though HKII(+/-) mice had significantly reduced (by 50%) hexokinase II mRNA and activity levels in skeletal muscle, heart, and adipose tissue, they did not exhibit impaired insulin action or glucose tolerance even when challenged with a high-fat diet [6].

Analytical, diagnostic and therapeutic context of Hk2

• The regulation of hexokinase II (HKII) was examined in fat and skeletal muscle of an animal model of non-insulin-dependent diabetes mellitus, the KKAY mouse [10].

References