RGD Reference Report - Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes. - Rat Genome Database

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Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes.

Authors: Ye, R  Ni, M  Wang, M  Luo, S  Zhu, G  Chow, RH  Lee, AS 
Citation: Ye R, etal., J Endocrinol. 2011 Aug;210(2):209-17. Epub 2011 May 12.
RGD ID: 6480678
Pubmed: PMID:21565852   (View Abstract at PubMed)
PMCID: PMC3137733   (View Article at PubMed Central)
DOI: DOI:10.1530/JOE-11-0012   (Journal Full-text)

The inositol 1,4,5-trisphosphate receptors (IP3Rs) as ligand-gated Ca(2)(+) channels are key modulators of cellular processes. Despite advances in understanding their critical role in regulating neuronal function and cell death, how this family of proteins impact cell metabolism is just emerging. Unexpectedly, a transgenic mouse line (D2D) exhibited progressive glucose intolerance as a result of transgene insertion. Inverse PCR was used to identify the gene disruption in the D2D mice. This led to the discovery that Itpr1 is among the ten loci disrupted in chromosome 6. Itpr1 encodes for IP3R1, the most abundant IP3R isoform in mouse brain and also highly expressed in pancreatic beta-cells. To study IP3R1 function in glucose metabolism, we used the Itpr1 heterozygous mutant mice, opt/+. Glucose homeostasis in male mice cohorts was examined by multiple approaches of metabolic phenotyping. Under regular diet, the opt/+ mice developed glucose intolerance but no insulin resistance. Decrease in second-phase glucose-stimulated blood insulin level was observed in opt/+ mice, accompanied by reduced beta-cell mass and insulin content. Strikingly, when fed with high-fat diet, the opt/+ mice were more susceptible to the development of hyperglycemia, glucose intolerance, and insulin resistance. Collectively, our studies identify the gene Itpr1 being interrupted in the D2D mice and uncover a novel role of IP3R1 in regulation of in vivo glucose homeostasis and development of diet-induced diabetes.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
diabetes mellitus susceptibilityISOItpr1 (Mus musculus)6480678; 6480678DNA:deletion:exon:p.Q1715_R1731del (mouse)RGD 
diabetes mellitus susceptibilityIAGP 6480678DNA:deletion:exon:p.Q1715_R1731del (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Itpr1  (inositol 1,4,5-trisphosphate receptor, type 1)

Genes (Mus musculus)
Itpr1  (inositol 1,4,5-trisphosphate receptor 1)

Genes (Homo sapiens)
ITPR1  (inositol 1,4,5-trisphosphate receptor type 1)


Additional Information