RGD Reference Report - Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model. - Rat Genome Database

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Altered gene expression involved in insulin signaling pathway in type II diabetic osteoporosis rats model.

Authors: Li, B  Wang, Y  Liu, Y  Ma, J  Li, Y 
Citation: Li B, etal., Endocrine. 2013 Feb;43(1):136-46. doi: 10.1007/s12020-012-9757-1. Epub 2012 Jul 22.
RGD ID: 7207063
Pubmed: PMID:22820932   (View Abstract at PubMed)
DOI: DOI:10.1007/s12020-012-9757-1   (Journal Full-text)

It is well established that both estrogen loss and type II diabetes mellitus (DMII) can impair bone metabolism, but whether estrogen loss exacerbates the effects of DMII is unclear. Therefore, we determined if ovariectomy (OVX) of rats on a long-term high-fat/sugar diet and injection of a low dose of streptozotocin (DMII) decreased bone mineral density (BMD) more than OVX or DMII alone. Bone insulin signaling is known to support bone metabolism; therefore, we also tested the hypothesis that OVX DMII rats (DOVX) would exhibit greater reductions in the expression of proteins important in insulin signaling, including IRS-1, IRS-2, and IGF-1. As hypothesized, BMD and plasma estrogen levels were decreased more in DOVX rats than in rats following OVX (NOVX) or DMII (DS) alone. IGF-1 expression was decreased in the liver, kidney, skeletal muscle, and bone of DOVX, DS, and NOVX rats; however, the decrease was larger and occurred sooner in DOVX rats. While IRS-1 and IRS-2 decreased in most groups in all tissues examined, the expression patterns differed in both a group- and tissue-dependent fashion. In conclusion, these data demonstrate that estrogen loss and DMII induced by a high-fat/sugar diet interact to produce osteoporosis and support the hypothesis that the bone loss may be mediated at least in part by concurrent decreases in the insulin signaling proteins in bone.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOIrs1 (Rattus norvegicus)7207063; 7207063mRNA and protein:decreased expression:multipleRGD 
Experimental Diabetes Mellitus  IEP 7207063mRNA and protein:decreased expression:multipleRGD 
osteoporosis  ISOIrs1 (Rattus norvegicus)7207063; 7207063mRNA and protein:decreased expression:multipleRGD 
osteoporosis  ISOIrs2 (Rattus norvegicus)7207063; 7207063associated with Diabetes Mellitus more ...RGD 
osteoporosis  IEP 7207063mRNA and protein:decreased expression:multipleRGD 
osteoporosis  IEP 7207063associated with Diabetes Mellitus more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Irs1  (insulin receptor substrate 1)
Irs2  (insulin receptor substrate 2)

Genes (Mus musculus)
Irs1  (insulin receptor substrate 1)
Irs2  (insulin receptor substrate 2)

Genes (Homo sapiens)
IRS1  (insulin receptor substrate 1)
IRS2  (insulin receptor substrate 2)


Additional Information