Decreased platelet phosphoinositide turnover and enhanced platelet activation in IDDM

Journal Article · Fri Sep 01 00:00:00 EDT 1989 · Diabetes; (USA)

DOI:https://doi.org/10.2337/diabetes.38.9.1097· OSTI ID:5408360

Bastyr, E.J. 3d.; Kadrofske, M M; Dershimer, R C; Vinik, A I ^[1]

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1. Univ. of Michigan, Ann Arbor (USA)

Individuals with diabetes mellitus may have increased in vivo platelet activity. Abnormal platelet function could contribute to the increased incidence of vascular disease in diabetes mellitus. The biochemical mechanism(s) for platelet hyperactivation is unknown. We examined the hypothesis that platelet phosphoinositide turnover, a key signal-transducing mechanism involved in platelet activation, was abnormal in diabetic subjects. Platelets were harvested from 16 subjects with insulin-dependent diabetes mellitus (IDDM) and 19 healthy, nondiabetic control subjects of comparable age. Plasma beta-thromboglobulin (beta-TBG), a specific marker of platelet activity in vivo, was increased in IDDM (67.1 +/- 7.3 ng/ml) compared with control (41.0 +/- 6.0 ng/ml) subjects (P less than .005). (32P)orthophosphate (32Pi) incorporation into the individual phosphoinositides and phosphatidic acid (PA) reached isotopic equilibrium by 120 min for IDDM and control subjects. Specific activity (dpm 32P/micrograms phosphorus) of phosphatidylinositol 4-phosphate (PIP) and phosphatidylinositol 4,5-bisphosphate (PIP2) was not different between IDDM and control subjects. Under these conditions, basal 32Pi incorporation into PIP2 and PIP but not phosphatidylinositol (PI) or PA was significantly lower in IDDM subjects. There was significantly decreased (32P)PIP2 and (32P)PIP hydrolysis and decreased (32P)PA formation in IDDM after platelet stimulation with 4 U/ml human thrombin. There were no differences in (32P)PI hydrolysis between the two groups. The mass of PIP2 was reduced (P less than .005) in the platelets from IDDM (0.71 +/- 0.23 nmol/10(9) platelets) compared with control (1.65 +/- 0.53 nmol/10(9) platelets) subjects. Similarly, PIP was lower (P less than .001) in IDDM (0.66 +/- 0.09 nmol/10(9) platelets) than in control (2.92 +/- 0.43 nmol/10(9) platelets) subjects.

• OSTI ID: 5408360
• Journal Information: Diabetes; (USA), Journal Name: Diabetes; (USA) Vol. 38:9; ISSN 0012-1797; ISSN DIAEA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MARKERS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BLOOD PLATELETS
BODY FLUIDS
DAYS LIVING RADIOISOTOPES
DIABETES MELLITUS
DISEASES
ENDOCRINE DISEASES
ESTERS
GLOBULINS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
MAMMALS
MAN
MATERIALS
METABOLIC DISEASES
METABOLISM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
OXYGEN COMPOUNDS
PATHOGENESIS
PHOSPHATES
PHOSPHOLIPIDS
PHOSPHORUS 32
PHOSPHORUS COMPOUNDS
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RADIOISOTOPES
TRACER TECHNIQUES
VERTEBRATES