RGD Reference Report - alpha2-Heremans Schmid glycoprotein, a putative inhibitor of tyrosine kinase, prevents glucose toxicity associated with cardiomyocyte dysfunction. - Rat Genome Database

RGD Reference Report - alpha2-Heremans Schmid glycoprotein, a putative inhibitor of tyrosine kinase, prevents glucose toxicity associated with cardiomyocyte dysfunction. - Rat Genome Database

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General

alpha2-Heremans Schmid glycoprotein, a putative inhibitor of tyrosine kinase, prevents glucose toxicity associated with cardiomyocyte dysfunction.
Authors:	Ren, J Davidoff, AJ
Citation:	Ren J and Davidoff AJ, Diabetes Metab Res Rev. 2002 Jul-Aug;18(4):305-10.
RGD ID:	8553811
Pubmed:	PMID:12203945 (View Abstract at PubMed)
DOI:	DOI:10.1002/dmrr.299 (Journal Full-text)
BACKGROUND: Diabetes leads to impaired glucose metabolism and insulin signaling in the heart, which may contribute to the development of diabetic cardiomyopathy. Insulin stimulates tyrosine phosphorylation of the insulin receptor and insulin receptor substrates. A two-fold increase in insulin-stimulated tyrosine phosphorylation has been reported in diabetic myocardium. The aim of the present study was to examine the effect of a putative inhibitor of tyrosine kinase phosphorylation, alpha(2)-Heremans Schmid glycoprotein (AHSG), on the mechanical dysfunction under a simulated diabetic environment. METHODS: Isolated ventricular myocytes from adult rats were maintained for 24 h in either normal glucose (NG, 5.5 mM) or high glucose (HG, 25.5 mM) medium with 10(-7) M insulin, and in the absence or presence of AHSG (50 micro g/ml). Contractile indices analyzed included: peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)) and area underneath shortening and relengthening (Area/PS). RESULTS: Myocytes maintained in HG medium displayed reduced PS and prolonged TPS/TR(90), with enhanced area, compared to the NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished by AHSG. Removal of insulin from the culture medium did not affect the basal myocyte mechanics, but prevented AHSG from completely protecting against the HG-induced mechanical defects (i.e. HG-induced prolongation of TR(90) and area were only partially attenuated by AHSG in the absence of insulin). CONCLUSIONS: The present data support the notion of tyrosine phosphorylation in the pathogenesis of diabetic cardiomyopathy, and implicate the therapeutic value of tyrosine kinase phosphorylation inhibitors.

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Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
kinase inhibitor activity	enables	NAS		8553811	PMID:12203945	UniProt

Objects Annotated

Genes (Rattus norvegicus)

Ahsg (alpha-2-HS-glycoprotein)

Additional Information