PMID- 10428828
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances 
      in glucose tolerance in heterozygotes.
PG  - 22517-23
AB  - 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.
FAU - Heikkinen, S
AU  - Heikkinen S
AD  - Department of Medicine, University of Kuopio, FIN-70211 Kuopio, Finland.
FAU - Pietila, M
AU  - Pietila M
FAU - Halmekyto, M
AU  - Halmekyto M
FAU - Suppola, S
AU  - Suppola S
FAU - Pirinen, E
AU  - Pirinen E
FAU - Deeb, S S
AU  - Deeb SS
FAU - Janne, J
AU  - Janne J
FAU - Laakso, M
AU  - Laakso M
LA  - eng
GR  - HL30086/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Dietary Fats)
RN  - 0 (Insulin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/enzymology
MH  - Animals
MH  - Chimera
MH  - Dietary Fats/pharmacology
MH  - Female
MH  - Fertility
MH  - Fetal Death
MH  - Genes, Lethal
MH  - Glucose/*metabolism
MH  - Glucose Tolerance Test
MH  - Heterozygote
MH  - Hexokinase/*deficiency/genetics
MH  - Homozygote
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Mice
MH  - Mice, Mutant Strains/embryology
MH  - Muscle, Skeletal/enzymology
MH  - Pregnancy
MH  - Stem Cells
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22517 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22517-23. doi: 10.1074/jbc.274.32.22517.