PMID- 7883123
OWN - NLM
STAT- MEDLINE
DCOM- 19950412
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 44
IP  - 3
DP  - 1995 Mar
TI  - Identification of four amino acid substitutions in hexokinase II and studies of 
      relationships to NIDDM, glucose effectiveness, and insulin sensitivity.
PG  - 347-53
AB  - Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, 
      plays a central role in glucose metabolism. Since reduced insulin-stimulated 
      glucose uptake and reduced glucose-6-phosphate content in muscle have been 
      demonstrated in pre-non-insulin-dependent diabetes mellitus (pre-NIDDM) and NIDDM 
      subjects, we have examined the coding region of the HKII gene in NIDDM patients 
      to determine whether these patients show genetic polymorphisms that are 
      associated with or contribute to the disease. Single-strand conformational 
      polymorphism analysis and nucleotide sequencing were initially performed on the 
      entire coding region of the HKII gene of 38 insulin-resistant NIDDM patients and 
      5 healthy control subjects. This analysis revealed four missense mutations at 
      codons 142 (Gln to His), 148 (Leu to Phe), 497 (Arg to Gln), and 844 (Arg to Lys) 
      and an additional six exon polymorphisms that did not predict any change in amino 
      acid composition of the protein. One homozygous and nine heterozygous carriers of 
      the codon 142 mutation were found among the NIDDM patients. The mutations at 
      codons 148, 497, and 844 were each found in one diabetic subject and only on one 
      allele. There were no carriers of compound heterozygous mutations. A subsequent 
      study of 301 patients with NIDDM and 151 healthy control subjects revealed no 
      additional mutations at codons 148, 497, or 844. The total frequency of the 
      mutated allele at codon 142 was 18.9% among the control subjects and 17.0% among 
      the NIDDM patients (chi 2 = 0.56, P = 0.45).(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Echwald, S M
AU  - Echwald SM
AD  - Steno Diabetes Center, Gentofte, Denmark.
FAU - Bjorbaek, C
AU  - Bjorbaek C
FAU - Hansen, T
AU  - Hansen T
FAU - Clausen, J O
AU  - Clausen JO
FAU - Vestergaard, H
AU  - Vestergaard H
FAU - Zierath, J R
AU  - Zierath JR
FAU - Printz, R L
AU  - Printz RL
FAU - Granner, D K
AU  - Granner DK
FAU - Pedersen, O
AU  - Pedersen O
LA  - eng
GR  - DK-46867/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
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  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Codon)
RN  - 0 (DNA Primers)
RN  - 0 (Insulin)
RN  - 982XCM1FOI (Tolbutamide)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
GS  - HKII
MH  - Adult
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Anthropometry
MH  - Base Sequence
MH  - Blood Glucose/drug effects/metabolism
MH  - Body Mass Index
MH  - Codon/genetics
MH  - DNA Primers
MH  - Diabetes Mellitus, Type 2/enzymology/*genetics/physiopathology
MH  - Exons
MH  - Genetic Carrier Screening
MH  - Glucose Tolerance Test
MH  - Hexokinase/*genetics
MH  - Homozygote
MH  - Humans
MH  - Insulin/pharmacology
MH  - Molecular Sequence Data
MH  - Physical Fitness
MH  - *Point Mutation
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Genetic
MH  - Precancerous Conditions/genetics
MH  - Reference Values
MH  - Restriction Mapping
MH  - Tolbutamide/pharmacology
EDAT- 1995/03/01 00:00
MHDA- 1995/03/01 00:01
CRDT- 1995/03/01 00:00
PHST- 1995/03/01 00:00 [pubmed]
PHST- 1995/03/01 00:01 [medline]
PHST- 1995/03/01 00:00 [entrez]
AID - 10.2337/diab.44.3.347 [doi]
PST - ppublish
SO  - Diabetes. 1995 Mar;44(3):347-53. doi: 10.2337/diab.44.3.347.