RGD Reference Report - Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling. - Rat Genome Database

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Reduced cardiotropic response to insulin in spontaneously hypertensive rats: role of peroxisome proliferator-activated receptor-gamma-initiated signaling.

Authors: Zhang, H  Li, J  Li, R  Zhang, Q  Ma, H  Ji, Q  Guo, W  Wang, H  Lopez, BL  Christopher, TA  Ma, X  Gao, F 
Citation: Zhang H, etal., J Hypertens. 2008 Mar;26(3):560-9.
RGD ID: 4108492
Pubmed: PMID:18300869   (View Abstract at PubMed)
DOI: DOI:10.1097/HJH.0b013e3282f343e1   (Journal Full-text)

OBJECTIVES: Vascular insulin resistance plays a crucial pathogenic role in the development of genetic hypertension. However, it is not known whether hypertension-associated myocardial insulin resistance also exists, and whether this is involved in the development of related diseases, such as hypertensive heart failure. The present study aimed to determine whether hypertension-associated myocardial insulin resistance exists, in addition to any underlying mechanism. METHODS: Ventricular myocytes were enzymatically isolated from male Wistar-Kyoto (WKY) rats or spontaneously hypertensive rats (SHR) and myocyte shortening and intracellular Ca2+ transient were assessed, as was any signaling mechanism. RESULTS: Compared with WKY rats, insulin-stimulated myocardial glucose uptake was blunted in SHR. More importantly, the positive inotropic effect of insulin was significantly reduced in SHR myocytes. Moreover, peroxisome proliferator-activated receptor (PPAR)gamma and phosphatidylinositol 3 (PI-3) kinase p85 expression and insulin-induced Akt phosphorylation were reduced in SHR cardiomyocytes, but were markedly restored when animals were treated with rosiglitazone for 14 days. Pretreatment with an Akt inhibitor abolished the inotropic effect induced by insulin in rosiglitazone-treated SHR cardiomyocytes. CONCLUSIONS: The data obtained demonstrate that insulin resistance exists in SHR cardiomyocytes as manifested by both reduced insulin-stimulated glucose uptake and an impaired contractile response to insulin, which is attributable to decreased PPARgamma expression and subsequent impairment in PI-3 kinase/Akt signaling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hypertension  ISOPik3r1 (Rattus norvegicus)4108492; 4108492protein:decreased expression:ventricular myocyte (rat)RGD 
hypertension  IEP 4108492protein:decreased expression:ventricular myocyte (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Mus musculus)
Pik3r1  (phosphoinositide-3-kinase regulatory subunit 1)

Genes (Homo sapiens)
PIK3R1  (phosphoinositide-3-kinase regulatory subunit 1)


Additional Information