PMID- 9287043
OWN - NLM
STAT- MEDLINE
DCOM- 19970925
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 46
IP  - 9
DP  - 1997 Sep
TI  - Changes in pancreatic islet glucokinase and hexokinase activities with increasing 
      age, obesity, and the onset of diabetes.
PG  - 1434-9
AB  - We examined changes in high- and low-Km glucose phosphorylating activity in 
      pancreatic islet extracts from the prediabetic Zucker diabetic fatty (ZDF) rat 
      between 5-6 weeks and 12 weeks of age (after the onset of diabetes). Comparisons 
      were made between the activity observed in the ZDF rat and that seen in the ZDF 
      lean control (ZLC) rat and the obese nondiabetic Zucker fatty (ZF) rat. At 5-6 
      weeks of age, insulin resistant ZDF and ZF rats were hyperinsulinemic, compared 
      with the ZLC rat, but had normal plasma glucose levels. Kinetic parameters (Vmax 
      and Km for glucose) of hexokinase (HK) and Km of glucokinase (GCK) did not differ 
      between groups. Islet GCK activity for ZDF and ZF rats was 1.7-fold greater than 
      in ZLC rats (P < 0.02 and P < 0.001, respectively). By 12 weeks of age, 
      hypersecretion of insulin at 5.0 mmol/l glucose was observed in perifused islets 
      from both obese groups relative to the ZLC rat. Islets from ZDF rats failed to 
      increase insulin secretion in response to increased glucose concentration. Group 
      differences in the kinetic parameters for GCK or in the Km values for HK were not 
      significant. Islet HK activity for ZDF and ZF rats was 1.9-fold (P < 0.05) and 
      1.7-fold (P < 0.05) greater, respectively, than for ZLC rats. Compared with the 
      5- to 6-week-old animals, HK activity increased 3.1-fold (P < 0.001), 2.5-fold (P 
      < 0.002), and 2.0-fold (P < 0.05) for ZDF, ZF, and ZLC rats, respectively. 
      Differences in GCK activity between 5- to 6- and 12-week-old rats were not 
      significant for any of the groups. We conclude: 1) increased islet glucose 
      phosphorylating activity is present in insulin resistant and hyperinsulinemic ZF 
      and ZDF rats, relative to the ZLC rat; 2) at 12 weeks of age, hyperinsulinemic 
      ZDF and ZF rats demonstrated significant increases in HK activity, compared with 
      lean controls; and 3) deficiency in GCK activity does not explain failure of 
      diabetic ZDF islets to respond to glucose, since differences between diabetic ZDF 
      and nondiabetic ZF rats were not statistically significant. Increases in 
      pancreatic islet phosphorylating activity seem to be important in maintaining 
      basal hyperinsulinemia in insulin-resistant animals, but do not appear to play a 
      role in the progression to glucose intolerance and diabetes.
FAU - Cockburn, B N
AU  - Cockburn BN
AD  - Howard Hughes Medical Institute and the Department of Biochemistry and Molecular 
      Biology, University of Chicago, Illinois 60637, USA.
FAU - Ostrega, D M
AU  - Ostrega DM
FAU - Sturis, J
AU  - Sturis J
FAU - Kubstrup, C
AU  - Kubstrup C
FAU - Polonsky, K S
AU  - Polonsky KS
FAU - Bell, G I
AU  - Bell GI
LA  - eng
GR  - DK-20595/DK/NIDDK NIH HHS/United States
GR  - DK-44840/DK/NIDDK 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  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.1.2 (Glucokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Glucokinase/genetics/*metabolism
MH  - Glucose/*metabolism
MH  - Hexokinase/*metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Insulin Secretion
MH  - Islets of Langerhans/*enzymology
MH  - Male
MH  - Obesity/*enzymology
MH  - Phosphorylation
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Mutant Strains
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
AID - 10.2337/diab.46.9.1434 [doi]
PST - ppublish
SO  - Diabetes. 1997 Sep;46(9):1434-9. doi: 10.2337/diab.46.9.1434.