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 g lucose uptake and utilization, reduced hexokinase II mRNA and enzyme produc tion, and low basal levels of glucose 6-phosphate in insulin-sensitive skel etal muscle and adipose tissues. Hexokinase II is primarily expressed in mu scle 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 k nock-out mouse. Mice homozygous for hexokinase II deficiency (HXII-/-) died at approximately 7.5 days post-fertilization, indicating that hexokinase I I is vital for mouse embryogenesis after implantation and before organogene sis, HKII+/- mice were viable, fertile, and grew normally. Surprisingly, ev en though HKII+/- mice had significantly reduced (by 50%) hexokinase II mRN A and activity levels in skeletal muscle, heart, and adipose tissue, they d id not exhibit impaired insulin action or glucose tolerance even when chall enged with a high-fat diet.