Protein kinase B in the diabetic heart
Date
2003
Authors
Huisamen B.
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Abstract
This 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.
Description
Keywords
glucose, insulin, isoprenaline, phosphatidylinositol 3 kinase, protein kinase B, protein tyrosine phosphatase inhibitor, streptozocin, vanadic acid, wortmannin, animal experiment, animal model, article, attenuation, controlled study, data analysis, disease association, enzyme activation, enzyme phosphorylation, enzyme regulation, experimental model, glucose transport, heart function, heart muscle, heart muscle cell, heart ventricle, insulin resistance, isolated heart, methodology, newborn, non insulin dependent diabetes mellitus, nonhuman, rat, rat strain, signal transduction, streptozocin diabetes, Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Disease Models, Animal, Enzyme Activation, Glucose, Insulin, Myocardium, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Rats, Rats, Zucker, Vanadates, Animalia
Citation
Molecular and Cellular Biochemistry
249
02-Jan
249
02-Jan