RGD Reference Report - c-Kit in early onset of diabetes: a morphological and functional analysis of pancreatic beta-cells in c-KitW-v mutant mice. - Rat Genome Database

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c-Kit in early onset of diabetes: a morphological and functional analysis of pancreatic beta-cells in c-KitW-v mutant mice.

Authors: Krishnamurthy, M  Ayazi, F  Li, J  Lyttle, AW  Woods, M  Wu, Y  Yee, SP  Wang, R 
Citation: Krishnamurthy M, etal., Endocrinology. 2007 Nov;148(11):5520-30. Epub 2007 Aug 2.
RGD ID: 2311230
Pubmed: PMID:17673521   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2007-0387   (Journal Full-text)

c-Kit tyrosine receptor kinase, a well-established stem cell marker, is expressed in a variety of tissues including the pancreas. The involvement of c-Kit in fetal rat and human endocrine pancreatic development, survival, and function has been well characterized but primarily using in vitro experimental approaches. Therefore, the aim of the current study was to examine whether deficiency of a functional c-Kit receptor would have physiological and functional implications in vivo. We characterized the c-Kit mutant mouse, c-Kit(W-v/+), to evaluate the in vivo role of c-Kit in beta-cell growth and function. Here we report that male c-Kit(W-v/+) mice, at 8 wk of age, showed high fasting blood glucose levels and impaired glucose tolerance, which was associated with low levels of insulin secretion after glucose stimulation in vivo and in isolated islets. Morphometric analysis revealed that beta-cell mass was significantly reduced (50%) in male c-Kit(W-v/+) mice when compared with controls (c-Kit(+/+)) (P < 0.05). In parallel, a reduction in pancreatic duodenal homeobox-1 and insulin gene expression in whole pancreas as well as isolated islets of c-Kit(W-v/+) male mice was noted along with a decrease in pancreatic insulin content. Furthermore, the reduction in beta-cell mass in male c-Kit(W-v/+) mice was associated with a decrease in beta-cell proliferation. Interestingly, these changes were not observed in female c-Kit(W-v/+) mice until 40 wk of age. Our results clearly demonstrate that the c-Kit receptor is involved in the regulation of glucose metabolism, likely through an important role in beta-cell development and function.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prediabetes syndrome  ISOPdx1 (Mus musculus)2311230; 2311230mRNA more ...RGD 
prediabetes syndrome  IEP 2311230mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Mus musculus)
Pdx1  (pancreatic and duodenal homeobox 1)

Genes (Homo sapiens)
PDX1  (pancreatic and duodenal homeobox 1)


Additional Information