PMID- 20878524
OWN - NLM
STAT- MEDLINE
DCOM- 20110216
LR  - 20211028
IS  - 1432-1777 (Electronic)
IS  - 0938-8990 (Print)
IS  - 0938-8990 (Linking)
VI  - 21
IP  - 9-10
DP  - 2010 Oct
TI  - Chromosomal mapping of pancreatic islet morphological features and regulatory 
      hormones in the spontaneously diabetic (Type 2) Goto-Kakizaki rat.
PG  - 499-508
LID - 10.1007/s00335-010-9285-3 [doi]
AB  - Insulin resistance and altered endocrine pancreas function are central 
      pathophysiological features of type 2 diabetes mellitus (T2DM). The Goto-Kakizaki 
      (GK) rat is a model of spontaneous T2DM characterised by reduced beta cell mass 
      and genetically determined glucose intolerance and altered insulin secretion. To 
      identify genetic determinants of endocrine pancreas histopathology, we carried 
      out quantitative trait locus (QTL) mapping of histological phenotypes (beta cell 
      mass -BCM and insulin-positive cell area -IPCA) and plasma concentration of 
      hormones and growth factors in a F2 cohort derived from GK and normoglycemic 
      Brown Norway rats. Although IPCA and BCM in the duodenal region of the pancreas 
      were highly positively correlated (P < 10(-6)), and similarly in the splenic 
      region, both measures were poorly correlated when comparing duodenal and splenic 
      phenotypes. Strongest evidence of linkage to pancreas morphological traits was 
      obtained between BCM and chromosome 10 (LOD 3.2). Evidence of significant linkage 
      (LOD 4.2) to plasma corticosterone was detected in a region of chromosome 1 
      distal to other QTLs previously identified in the GK. Male-specific genetic 
      effects were detected, including linkages (LOD > 4) to growth hormome (GH) on 
      chromosome 6 and prolactin on chromosome 17. These data suggest independent 
      genetic control of the structure and function of ontologically different regions 
      of the endocrine pancreas. Novel QTLs for corticosterone, prolactin and GH may 
      contribute to diabetes in the GK. The QTLs that we have identified in this, and 
      previous genetic studies collectively underline the complex and multiple 
      mechanisms involved in diabetes in the GK strain.
FAU - Finlay, Clare
AU  - Finlay C
AD  - The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt 
      Drive, Headington, Oxford, OX3 7BN, UK.
FAU - Argoud, Karene
AU  - Argoud K
FAU - Wilder, Steven P
AU  - Wilder SP
FAU - Ouali, Fetta
AU  - Ouali F
FAU - Ktorza, Alain
AU  - Ktorza A
FAU - Kaisaki, Pamela J
AU  - Kaisaki PJ
FAU - Gauguier, Dominique
AU  - Gauguier D
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100929
PL  - United States
TA  - Mamm Genome
JT  - Mammalian genome : official journal of the International Mammalian Genome Society
JID - 9100916
RN  - 0 (Blood Glucose)
RN  - 0 (Genetic Markers)
RN  - 0 (Insulin)
RN  - 9002-62-4 (Prolactin)
RN  - 9002-72-6 (Growth Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Blood Glucose
MH  - Chromosome Mapping
MH  - Corticosterone/blood
MH  - Crosses, Genetic
MH  - Diabetes Mellitus, Type 2/*genetics/*metabolism/*pathology
MH  - Disease Models, Animal
MH  - Female
MH  - Genetic Linkage
MH  - Genetic Markers
MH  - Genetic Predisposition to Disease
MH  - Growth Hormone/blood/genetics
MH  - Insulin/blood/genetics
MH  - Insulin-Secreting Cells/*metabolism
MH  - Islets of Langerhans/metabolism/*pathology/ultrastructure
MH  - Male
MH  - Pancreas/pathology
MH  - Phenotype
MH  - Prolactin/blood/genetics
MH  - *Quantitative Trait Loci
MH  - Rats
MH  - Rats, Inbred BN
PMC - PMC2974204
EDAT- 2010/09/30 06:00
MHDA- 2011/02/17 06:00
PMCR- 2010/09/29
CRDT- 2010/09/30 06:00
PHST- 2010/07/04 00:00 [received]
PHST- 2010/09/01 00:00 [accepted]
PHST- 2010/09/30 06:00 [entrez]
PHST- 2010/09/30 06:00 [pubmed]
PHST- 2011/02/17 06:00 [medline]
PHST- 2010/09/29 00:00 [pmc-release]
AID - 9285 [pii]
AID - 10.1007/s00335-010-9285-3 [doi]
PST - ppublish
SO  - Mamm Genome. 2010 Oct;21(9-10):499-508. doi: 10.1007/s00335-010-9285-3. Epub 2010 
      Sep 29.