Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.
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.
Heikkinen
S
S
Department of Medicine, University of Kuopio, FIN-70211 Kuopio, Finland.
Pietilä
M
M
Halmekytö
M
M
Suppola
S
S
Pirinen
E
E
Deeb
S S
SS
Jänne
J
J
Laakso
M
M
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
D004041:Dietary Fats; D007328:Insulin; D006593:Hexokinase; D005947:Glucose