Store-operated Ca(2+) entry and tyrosine kinase pp60(src) hyperactivity are modulated by hyperglycemia in platelets from patients with non insulin-dependent diabetes mellitus.
We have investigated the involvement of store-operated Ca(2+) entry (SOCE) in the abnormal platelet Ca(2+) homeostasis in patients with non insulin-dependent diabetes mellitus (NIDDM). In a medium containing 180 mg/dL glucose, platelets from NIDDM patients showed an increased SOCE compared to controls. We found that tyrosine phosphorylation was elevated in platelets from NIDDM patients. Consistent with this, the activity of the tyrosine kinase pp60(src) is enhanced in platelets from diabetic patients. When the experiments were performed in a medium containing 90 mg/dL both, SOCE and pp60(src) activity, were similar to those found in control platelets. Our results indicate that SOCE is altered in platelets from NIDDM patients probably due to the increased activity of the tyrosine kinase pp60(src). Both, SOCE and pp60(src) activity in platelets from NIDDM patients are more susceptible to the extracellular glucose concentration, which seems to be involved in the dysfunction of these mechanisms.
Saavedra
Fernando R
FR
Department of Physiology, University of Extremadura, 10071 Cáceres, Spain.
Redondo
Pedro C
PC
Hernández-Cruz
Juan M
JM
Salido
Gines M
GM
Pariente
Jose A
JA
Rosado
Juan A
JA
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src) / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D011505:Protein-Tyrosine Kinases; D015688:Oncogene Protein pp60(v-src); D005947:Glucose; D002118:Calcium