Changes in phosphoinositide turnover, Ca sup 2+ mobilization, and protein phosphorylation in platelets from NIDDM patients

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Diabetes; (USA)

DOI:https://doi.org/10.2337/diab.39.12.1561· OSTI ID:6321280

Ishii, H; Umeda, F; Hashimoto, T; Nawata, H ^[1]

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1. Kyushu Univ., Fukuoka (Japan)

Enhanced platelet functions have been demonstrated in patients with non-insulin-dependent diabetes mellitus (NIDDM). This study evaluated abnormalities in platelet signal transduction in diabetic patients, including turnover of phosphoinositides, mobilization of intracellular Ca2+, and phosphorylation of 20,000- and 47,000-Mr proteins (P20 and P47). Washed platelets were obtained from 6 patients with NIDDM whose platelet aggregation rates were abnormally elevated (DM-A group), 11 NIDDM patients with normal platelet aggregation rates (DM-B group), and 8 age-matched healthy control subjects. The mass and specific radioactivity of phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), and phosphatidic acid (PA) in 32P-labeled platelets were not different among the three groups. Hydrolysis of PIP2, PIP, and PI; accumulation of PA; and phosphorylation of P20 in platelets stimulated by 0.05 U/ml thrombin were significantly increased in the DM-A group compared with the control or DM-B group. There was no difference in P47 phosphorylation among the three groups. On the contrary, P20 and P47 phosphorylation induced by 50 nM of 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, was significantly decreased in the DM-A group. Additionally, the intracellular free Ca2+ concentration (( Ca2+)i) was measured with the fluorescent Ca2+ indicator fura 2. Although the basal (Ca2+)i value was similar in the three groups, the rise in (Ca2+)i induced by 0.05 U/ml thrombin in the presence and the absence of extracellular Ca2+ was significantly higher in the DM-A group than the other groups.

• OSTI ID: 6321280
• Journal Information: Diabetes; (USA), Vol. 39:12; ISSN 0012-1797
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BLOOD PLATELETS
BLOOD COAGULATION
DIABETES MELLITUS
PATHOGENESIS
PHORBOL ESTERS
BIOLOGICAL EFFECTS
PHOSPHOLIPIDS
METABOLISM
CALCIUM COMPOUNDS
FLUORESCENCE
PATIENTS
PHOSPHORUS 32
PHOSPHORYLATION
THROMBIN
TRACER TECHNIQUES
ALKALINE EARTH METAL COMPOUNDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CHEMICAL REACTIONS
COAGULANTS
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ENDOCRINE DISEASES
ENZYMES
ESTERS
HEMATOLOGIC AGENTS
HEMOSTATICS
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
LUMINESCENCE
MATERIALS
METABOLIC DISEASES
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PEPTIDE HYDROLASES
PHOSPHORUS ISOTOPES
RADIOISOTOPES
SERINE PROTEINASES
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