title: Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.
abstract: Type 2 diabetes is characterized by decreased rates of insulin-stimulated glucose uptake and utilization, reduced hexokinase II mRNA and enzyme production, and low basal levels of glucose 6-phosphate in insulin-sensitive skeletal muscle and adipose tissues. Hexokinase II is primarily expressed in muscle and adipose tissues where it catalyzes the phosphorylation of glucose to glucose 6-phosphate, a possible rate-limiting step for glucose disposal. To investigate the role of hexokinase II in insulin action and in glucose homeostasis as well as in mouse development, we generated a hexokinase II knock-out mouse. 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. HKII(+/-) mice were viable, fertile, and grew normally. 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.
authors.affiliation: Department of Medicine, University of Kuopio, FIN-70211 Kuopio, Finland.
authors.forename: S
authors.initials: S
authors.lastname: Heikkinen
authors.forename: M
authors.initials: M
authors.lastname: Pietilä
authors.forename: M
authors.initials: M
authors.lastname: Halmekytö
authors.forename: S
authors.initials: S
authors.lastname: Suppola
authors.forename: E
authors.initials: E
authors.lastname: Pirinen
authors.forename: S S
authors.initials: SS
authors.lastname: Deeb
authors.forename: J
authors.initials: J
authors.lastname: Jänne
authors.forename: M
authors.initials: M
authors.lastname: Laakso
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D002678:Chimera; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D005298:Fertility; D005313:Fetal Death; D005804:Genes, Lethal; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006593:Hexokinase / Q000172:deficiency* / Q000235:genetics; D006720:Homozygote; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000196:embryology; D018482:Muscle, Skeletal / Q000201:enzymology; D011247:Pregnancy; D013234:Stem Cells
chemical_list: D004041:Dietary Fats; D007328:Insulin; D006593:Hexokinase; D005947:Glucose