DMA Group Research Articles

Changes in Phosphoinositide Turnover, Ca2+ Mobilization, and Protein Phosphorylation in Platelets From NIDDM Patients

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of diabetic microangiopathy and neuropathy among Japanese diabetics in the Tokyo area: related to the WHO new diagnostic criteria.

In accordance with the new criteria for diabetes mellitus proposed by the WHO in 1980, patients treated at our clinic from 1976 to 1980 were examined for diabetes mellitus and its three major complications. 3809 patients (M 2176, F 1630) were divided into three groups: DM-A group (2912) with fasting plasma glucose (FPG) greater than or equal to 140 mg/100 ml; DM-B group (334) with FPG less than 140 and 2 hr after load (2H) greater than or equal to 200; IGT group (563) with FPG less than 140 and 140 less than or equal to 2H less than 200. The prevalences of the three complications are presented in the order: DM-A; DM-B; IGT, 33%; 21%; 15% (proteinuria), 48%; 28%; 18% (retinopathy), 63%; 47%; 34% (neuropathy), 15%; 6%; 1% (triopathy). Among the diabetics groups (DM-A + DM-B), prevalence of retinopathy is examined by sex, known duration of diabetes and age at registration. Prevalence is 45% in male, and 47% in female; duration 0-2 yr 27%, 3-5 yr 37%, 6-8 yr 50%, 9-11 yr 59%, 12-14 yr 68%, 15 yr- 73%; age at registration 0-24 yr 23%, 25-44 yr 39%, 45-64 yr 50%, 65 yr- 47%. On crosstabulation of age and duration in 25-44 yr age group, the prevalence of retinopathy as a function of known duration is 22% (duration 0-2 yr), 29% (3-5 yr), 53% (6-8 yr), 62% (9-11 yr), 73% (12-14 yr), 90% (15 yr-) and the prevalence rises more steeply than elder ones.(ABSTRACT TRUNCATED AT 250 WORDS)