Platelets and vascular smooth muscle: abnormalities of phosphodiesterase, aggregation, and cell growth in experimental and human diabetes.
Platelets appear to be involved in both the maintenance of homeostasis and the regulation of proliferation of vascular smooth muscle cells. Anomalies of platelet function may be responsible in part for the pathogenesis of vascular disease in experimental and human diabetes. In a search for an appropriate animal model, we have studied platelet function and the properties of platelet cyclic NCL-PDE in rats with streptozocin-induced diabetes, spontaneous diabetes, and human insulin-dependent diabetes mellitus (IDDM). It appears that opposite abnormalities in both aggregation and phosphodiesterase activity exist in the two animal models. In human IDDM, similar abnormalities to those seen in the BB model were observed. Vascular smooth muscle cells in culture can be used as a model for studies of the effect of circulating growth factors in animals and humans. A growth inhibitory factor was found in plasma and serum from STZ and human IDDM but not BB. In humans we observed increased growth-promoting activity of diabetic platelets, but this phenomenon was absent in both animal models. It remains to be evaluated whether these differences may account for the fact that diabetic rats appear resistant to development of vascular complications. It also remains to be established which animal model is the best choice for studying growth abnormalities in diabetes.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000097:blood; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D010974:Platelet Aggregation; D051381:Rats
D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D015056:1-Methyl-3-isobutylxanthine