RGD Reference Report - Chromosomal mapping of pancreatic islet morphological features and regulatory hormones in the spontaneously diabetic (Type 2) Goto-Kakizaki rat. - Rat Genome Database

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Chromosomal mapping of pancreatic islet morphological features and regulatory hormones in the spontaneously diabetic (Type 2) Goto-Kakizaki rat.

Authors: Finlay, C  Argoud, K  Wilder, SP  Ouali, F  Ktorza, A  Kaisaki, PJ  Gauguier, D 
Citation: Finlay C, etal., Mamm Genome. 2010 Oct;21(9-10):499-508. Epub 2010 Sep 29.
RGD ID: 4889455
Pubmed: PMID:20878524   (View Abstract at PubMed)
PMCID: PMC2974204   (View Article at PubMed Central)
DOI: DOI:10.1007/s00335-010-9285-3   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GK/OxRathyperglycemia  IAGP  RGD 
GK/OxRatInsulin Resistance  IAGP compared to BN/CrlRGD 
GK/OxRattype 2 diabetes mellitus MODELIAGP compared to BN/CrlRGD 
Pancm2Rattype 2 diabetes mellitus  IAGP  RGD 
Scort2Rattype 2 diabetes mellitus  IAGP  RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Scort2Ratdecreased circulating corticosterone level  IDA  RGD 
GK/OxRatdecreased insulin secretion susceptibilityIAGP compared to BN/CrlRGD 
GK/OxRatdecreased pancreatic beta cell mass susceptibilityIAGP compared to BN/CrlRGD 
Pancm2Ratdecreased pancreatic beta cell mass  IDA  RGD 
GK/OxRatdecreased prolactin level sexual_dimorphism IAGP compared to male BN/CrlRGD 
GK/OxRatimpaired glucose tolerance susceptibilityIAGP compared to BN/CrlRGD 
BN/CrlRatincreased body weight sexual_dimorphism IAGP compared to female BN/CrlRGD 
GK/OxRatincreased body weight sexual_dimorphism IAGP compared to female GK/OxRGD 
GK/OxRatincreased body weight susceptibilityIAGP compared to BN/CrlRGD 
GK/OxRatincreased circulating corticosterone level sexual_dimorphismIAGP compared to male BN/CrlRGD 
GK/OxRatincreased circulating glucose level susceptibilityIAGP compared to BN/CrlRGD 
GK/OxRatincreased circulating insulin level sexual_dimorphism IAGP compared to female GK/OxRGD 
GK/OxRatincreased circulating insulin level susceptibilityIAGP compared to BN/CrlRGD 
BN/CrlRatincreased circulating insulin-like growth factor I level sexual_dimorphism IAGP male compared to femaleRGD 
GK/OxRatincreased circulating insulin-like growth factor I level sexual_dimorphism IAGP male compared to femaleRGD 
BN/CrlRatincreased growth hormone level sexual_dimorphism IAGP female compared to male BN/CrlRGD 
BN/CrlRatincreased prolactin level sexual_dimorphism IAGP compared to male BN/CrlRGD 
GK/OxRatincreased prolactin level sexual_dimorphismIAGP compared to male GK/OxRGD 
GK/OxRatinsulin resistance susceptibilityIAGP compared to BN/CrlRGD 

Objects Annotated

QTLs
Pancm2  (Pancreatic morphology QTL 2)
Scort2  (Serum corticosterone level QTL 2)

Strains
BN/Crl  (NA)
GK/Ox  (NA)


Additional Information