PMID- 19910451
OWN - NLM
STAT- MEDLINE
DCOM- 20100301
LR  - 20211020
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 204
IP  - 2
DP  - 2010 Feb
TI  - Reduction of islet pyruvate carboxylase activity might be related to the 
      development of type 2 diabetes mellitus in Agouti-K mice.
PG  - 143-52
LID - 10.1677/JOE-09-0391 [doi]
AB  - Pyruvate carboxylase (PC) activity is enhanced in the islets of obese rats, but 
      it is reduced in the islets of type 2 diabetic rats, suggesting the importance of 
      PC in beta-cell adaptation to insulin resistance as well as the possibility that 
      PC reduction might lead to hyperglycemia. However, the causality is currently 
      unknown. We used obese Agouti mice (AyL) as a model to show enhanced beta-cell 
      adaptation, and type 2 diabetic db/db mice as a model to show severe beta-cell 
      failure. After comparison of the two models, a less severe type 2 diabetic 
      Agouti-K (AyK) mouse model was used to show the changes in islet PC activity 
      during the development of type 2 diabetes mellitus (T2DM). AyK mice were 
      separated into two groups: mildly (AyK-M, blood glucose <250 mg/dl) and severely 
      (AyK-S, blood glucose >250 mg/dl) hyperglycemic. Islet PC activity, but not 
      protein level, was increased 1.7-fold in AyK-M mice; in AyK-S mice, islet PC 
      activity and protein level were reduced. All other changes including insulin 
      secretion and islet morphology in AyK-M mice were similar to those observed in 
      AyL mice, but they were worse in AyK-S mice where these parameters closely 
      matched those in db/db mice. In 2-day treated islets, PC activity was inhibited 
      by high glucose but not by palmitate. Our findings suggest that islet PC might 
      play a role in the development of T2DM where reduction of PC activity might be a 
      consequence of mild hyperglycemia and a cause for severe hyperglycemia.
FAU - Han, J
AU  - Han J
AD  - The Research Institute for Children, Children's Hospital at New Orleans, New 
      Orleans, Louisiana 70118, USA.
FAU - Liu, Y Q
AU  - Liu YQ
LA  - eng
GR  - 1R01DK077624-01/DK/NIDDK NIH HHS/United States
GR  - R01 DK077624-01/DK/NIDDK NIH HHS/United States
GR  - P20 RR017702-06A16817/RR/NCRR NIH HHS/United States
GR  - R01 DK077624-02/DK/NIDDK NIH HHS/United States
GR  - P20 RR017702/RR/NCRR NIH HHS/United States
GR  - P20 RR/DE17702/DE/NIDCR NIH HHS/United States
GR  - R01 DK077624/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20091112
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids)
RN  - 0 (Insulin)
RN  - 0 (Pyruvate Dehydrogenase Complex)
RN  - 2V16EO95H1 (Palmitic Acid)
RN  - EC 6.4.1.1 (Pyruvate Carboxylase)
SB  - IM
MH  - Aging/metabolism
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Type 2/*enzymology/etiology
MH  - Fatty Acids/metabolism
MH  - Glucose Tolerance Test
MH  - Hyperglycemia/*metabolism
MH  - Insulin/blood/metabolism
MH  - Insulin Secretion
MH  - Islets of Langerhans/*enzymology
MH  - Male
MH  - Mice
MH  - Mice, Obese
MH  - Palmitic Acid/metabolism
MH  - Pyruvate Carboxylase/*metabolism
MH  - Pyruvate Dehydrogenase Complex/metabolism
PMC - PMC2808427
MID - NIHMS159255
EDAT- 2009/11/17 06:00
MHDA- 2010/03/02 06:00
PMCR- 2011/02/01
CRDT- 2009/11/14 06:00
PHST- 2009/11/14 06:00 [entrez]
PHST- 2009/11/17 06:00 [pubmed]
PHST- 2010/03/02 06:00 [medline]
PHST- 2011/02/01 00:00 [pmc-release]
AID - JOE-09-0391 [pii]
AID - 10.1677/JOE-09-0391 [doi]
PST - ppublish
SO  - J Endocrinol. 2010 Feb;204(2):143-52. doi: 10.1677/JOE-09-0391. Epub 2009 Nov 12.