Protein kinase B in the diabetic heart

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dc.contributor.authorHuisamen B.
dc.date.accessioned2011-05-15T16:00:00Z
dc.date.available2011-05-15T16:00:00Z
dc.date.issued2003
dc.description.abstractThis paper summarizes data from different studies all aimed at elucidating regulation of protein kinase B in the diabetic heart. Two rat models of type 2 diabetes mellitus ((i) elicited via neonatal streptozotocin injection (Stz) and (ii) Zucker fa/fa rats), were used as well as different experimental models viz isolated, Langendorff perfused hearts as well as adult ventricular myocytes. Glucose uptake was elicited by a variety of stimuli and the activation of PKB measured in tandem. Basal glucose uptake was impaired in both diabetes models while basal phosphorylation of PKB differed, showing lower levels in the Stz model but higher levels in the Zucker rats. Neither 100 nM insulin nor 10-8 M isoproterenol could stimulate PKB phosphorylation to the same extent in the diabetic myocardium as in controls, regardless of the method used, but a combination of these stimuli resulted in an additive response. Concurrent glucose uptake however, was not additive. Wortmannin abolished both insulin and isoproterenol stimulation of glucose uptake as well as PKB phosphorylation. In contrast to the above-mentioned results, the protein tyrosine phosphatase inhibitor vanadate, alone or in combination with insulin, elicited PKB phosphorylation to the same extent in diabetic cardiomyocytes as in controls. Despite this, glucose uptake stimulated by vanadate or insulin in combination with vanadate was attenuated. The combination of insulin and vanadate may however be beneficial to the diabetic heart as it resulted in improved glucose transport. Results from the different studies can be summarized as follows: (i) dysregulation of PKB is evident in the diabetic myocardium, (ii) PKB activation is not always directly correlated with glucose uptake and (iii) insulin resistance is associated with multiple alterations in signal transduction, both above and below PKB activation.
dc.description.versionArticle
dc.identifier.citationMolecular and Cellular Biochemistry
dc.identifier.citation249
dc.identifier.citation02-Jan
dc.identifier.issn3008177
dc.identifier.other10.1023/A:1024749614222
dc.identifier.urihttp://hdl.handle.net/10019.1/11477
dc.subjectglucose
dc.subjectinsulin
dc.subjectisoprenaline
dc.subjectphosphatidylinositol 3 kinase
dc.subjectprotein kinase B
dc.subjectprotein tyrosine phosphatase inhibitor
dc.subjectstreptozocin
dc.subjectvanadic acid
dc.subjectwortmannin
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectarticle
dc.subjectattenuation
dc.subjectcontrolled study
dc.subjectdata analysis
dc.subjectdisease association
dc.subjectenzyme activation
dc.subjectenzyme phosphorylation
dc.subjectenzyme regulation
dc.subjectexperimental model
dc.subjectglucose transport
dc.subjectheart function
dc.subjectheart muscle
dc.subjectheart muscle cell
dc.subjectheart ventricle
dc.subjectinsulin resistance
dc.subjectisolated heart
dc.subjectmethodology
dc.subjectnewborn
dc.subjectnon insulin dependent diabetes mellitus
dc.subjectnonhuman
dc.subjectrat
dc.subjectrat strain
dc.subjectsignal transduction
dc.subjectstreptozocin diabetes
dc.subjectAnimals
dc.subjectDiabetes Mellitus, Experimental
dc.subjectDiabetes Mellitus, Type 2
dc.subjectDisease Models, Animal
dc.subjectEnzyme Activation
dc.subjectGlucose
dc.subjectInsulin
dc.subjectMyocardium
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectProto-Oncogene Proteins
dc.subjectProto-Oncogene Proteins c-akt
dc.subjectRats
dc.subjectRats, Zucker
dc.subjectVanadates
dc.subjectAnimalia
dc.titleProtein kinase B in the diabetic heart
dc.typeArticle
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