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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hyperglycemia  IAGP 4889455 RGD 
Insulin Resistance  IAGP 4889455compared to BN/CrlRGD 
type 2 diabetes mellitus MODELIAGP 4889455compared to BN/CrlRGD 
type 2 diabetes mellitus  IAGP 4889455; 4889455 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased circulating corticosterone level  IDA 4889455 RGD 
decreased insulin secretion susceptibilityIAGP 4889455compared to BN/CrlRGD 
decreased pancreatic beta cell mass susceptibilityIAGP 4889455compared to BN/CrlRGD 
decreased pancreatic beta cell mass  IDA 4889455 RGD 
decreased prolactin level sexual_dimorphism IAGP 4889455compared to male BN/CrlRGD 
impaired glucose tolerance susceptibilityIAGP 4889455compared to BN/CrlRGD 
increased body weight sexual_dimorphism IAGP 4889455compared to female BN/CrlRGD 
increased body weight sexual_dimorphism IAGP 4889455compared to female GK/OxRGD 
increased body weight susceptibilityIAGP 4889455compared to BN/CrlRGD 
increased circulating corticosterone level sexual_dimorphismIAGP 4889455compared to male BN/CrlRGD 
increased circulating glucose level susceptibilityIAGP 4889455compared to BN/CrlRGD 
increased circulating insulin level sexual_dimorphism IAGP 4889455compared to female GK/OxRGD 
increased circulating insulin level susceptibilityIAGP 4889455compared to BN/CrlRGD 
increased circulating insulin-like growth factor I level sexual_dimorphism IAGP 4889455; 4889455male compared to femaleRGD 
increased growth hormone level sexual_dimorphism IAGP 4889455female compared to male BN/CrlRGD 
increased prolactin level sexual_dimorphism IAGP 4889455compared to male BN/CrlRGD 
increased prolactin level sexual_dimorphismIAGP 4889455compared to male GK/OxRGD 
insulin resistance susceptibilityIAGP 4889455compared 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