PMID- 25660120
OWN - NLM
STAT- MEDLINE
DCOM- 20151203
LR  - 20181202
IS  - 1432-0428 (Electronic)
IS  - 0012-186X (Linking)
VI  - 58
IP  - 4
DP  - 2015 Apr
TI  - Disruption of CR6-interacting factor-1 (CRIF1) in mouse islet beta cells leads to 
      mitochondrial diabetes with progressive beta cell failure.
PG  - 771-80
LID - 10.1007/s00125-015-3506-y [doi]
AB  - AIM/HYPOTHESIS: Although mitochondrial oxidative phosphorylation (OxPhos) 
      dysfunction is believed to be responsible for beta cell dysfunction in insulin 
      resistance and mitochondrial diabetes, the mechanisms underlying progressive beta 
      cell failure caused by defective mitochondrial OxPhos are largely unknown. 
      METHODS: We examined the in vivo phenotypes of beta cell dysfunction in beta 
      cell-specific Crif1 (also known as Gadd45gip1)-deficient mice. CR6-interacting 
      factor-1 (CRIF1) is a mitochondrial protein essential for the synthesis and 
      formation of the OxPhos complex in the inner mitochondrial membrane. RESULTS: 
      Crif1(beta-/-) mice exhibited impaired glucose tolerance with defective insulin 
      secretion as early as 4 weeks of age without defects in islet structure. At 11 
      weeks of age, Crif1(beta-/-) mice displayed characteristic ultrastructural 
      mitochondrial abnormalities as well as severe glucose intolerance. Furthermore, 
      islet area and insulin content was decreased by approximately 50% compared with 
      wild-type mice. Treatment with the glucoregulatory drug exenatide, a 
      glucagon-like peptide-1 (GLP-1) agonist, was not sufficient to preserve beta cell 
      function in Crif1(beta-/-) mice. CONCLUSIONS/INTERPRETATION: Our results indicate 
      that mitochondrial OxPhos dysfunction triggers progressive beta cell failure that 
      is not halted by treatment with a GLP-1 agonist. The Crif1(beta-/-) mouse is a 
      useful model for the study of beta cell failure caused by mitochondrial OxPhos 
      dysfunction.
FAU - Kim, Yong Kyung
AU  - Kim YK
AD  - Research Center for Endocrine and Metabolic Diseases, Chungnam National 
      University School of Medicine, Daejeon, 301-721, Korea.
FAU - Joung, Kyong Hye
AU  - Joung KH
FAU - Ryu, Min Jeong
AU  - Ryu MJ
FAU - Kim, Soung Jung
AU  - Kim SJ
FAU - Kim, Hyeongseok
AU  - Kim H
FAU - Chung, Hyo Kyun
AU  - Chung HK
FAU - Lee, Min Hee
AU  - Lee MH
FAU - Lee, Seong Eun
AU  - Lee SE
FAU - Choi, Min Jeong
AU  - Choi MJ
FAU - Chang, Joon Young
AU  - Chang JY
FAU - Hong, Hyun Jung
AU  - Hong HJ
FAU - Kim, Koon Soon
AU  - Kim KS
FAU - Lee, Sang-Hee
AU  - Lee SH
FAU - Kweon, Gi Ryang
AU  - Kweon GR
FAU - Kim, Hail
AU  - Kim H
FAU - Lee, Chul-Ho
AU  - Lee CH
FAU - Kim, Hyun Jin
AU  - Kim HJ
FAU - Shong, Minho
AU  - Shong M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150208
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Blood Glucose)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Crif1 protein, mouse)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Incretins)
RN  - 0 (Insulin)
RN  - 0 (Peptides)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - Age Factors
MH  - Animals
MH  - Autophagy
MH  - Blood Glucose/metabolism
MH  - Cell Cycle Proteins/*deficiency/genetics
MH  - Cell Line
MH  - Diabetes Mellitus/drug therapy/genetics/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Exenatide
MH  - Genotype
MH  - Glucagon-Like Peptide-1 Receptor/agonists/metabolism
MH  - Hypoglycemic Agents/pharmacology
MH  - Incretins/pharmacology
MH  - Insulin/blood
MH  - Insulin-Secreting Cells/drug effects/*metabolism/ultrastructure
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitochondria/drug effects/*metabolism/ultrastructure
MH  - *Oxidative Phosphorylation
MH  - Peptides/pharmacology
MH  - Phenotype
MH  - Time Factors
MH  - Venoms/pharmacology
EDAT- 2015/02/11 06:00
MHDA- 2015/12/15 06:00
CRDT- 2015/02/10 06:00
PHST- 2014/09/24 00:00 [received]
PHST- 2014/12/30 00:00 [accepted]
PHST- 2015/02/10 06:00 [entrez]
PHST- 2015/02/11 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - 10.1007/s00125-015-3506-y [doi]
PST - ppublish
SO  - Diabetologia. 2015 Apr;58(4):771-80. doi: 10.1007/s00125-015-3506-y. Epub 2015 
      Feb 8.