A Novel Small Molecule 1,2,3,4,6-penta-O-galloyl-α-D-glucopyranose Mimics the Antiplatelet Actions of Insulin

BACKGROUND: We have shown that 1,2,3,4,6-penta-O-galloyl-α-D-glucopyranose (α-PGG), an orally effective hypoglycemic small molecule, binds to insulin receptors and activates insulin-mediated glucose transport. Insulin has been shown to bind to its receptors on platelets and inhibit platelet activation. In this study we tested our hypothesis that if insulin possesses anti-platelet properties then insulin mimetic small molecules should mimic antiplatelet actions of insulin. PRINCIPAL FINDINGS: Incubation of human platelets with insulin or α-PGG induced phosphorylation of insulin receptors and IRS-1 and blocked ADP or collagen induced aggregation. Pre-treatment of platelets with α-PGG inhibited thrombin-induced release of P-selectin, secretion of ATP and aggregation. Addition of ADP or thrombin to platelets significantly decreased the basal cyclic AMP levels. Pre-incubation of platelets with α-PGG blocked ADP or thrombin induced decrease in platelet cyclic AMP levels but did not alter the basal or PGE(1) induced increase in cAMP levels. Addition of α-PGG to platelets blocked agonist induced rise in platelet cytosolic calcium and phosphorylation of Akt. Administration of α-PGG (20 mg kg(-1)) to wild type mice blocked ex vivo platelet aggregation induced by ADP or collagen. CONCLUSIONS: These data suggest that α-PGG inhibits platelet activation, at least in part, by inducing phosphorylation of insulin receptors leading to inhibition of agonist induced: (a) decrease in cyclic AMP; (b) rise in cytosolic calcium; and (c) phosphorylation of Akt. These findings taken together with our earlier reports that α-PGG mimics insulin signaling suggest that inhibition of platelet activation by α-PGG mimics antiplatelet actions of insulin

Low-input cropping systems to reduce input dependency and environmental impacts in maize production: A multi-criteria assessment

International audienceIntensification of cropping systems in recent decades has increased their productivity but affected air, soil and water quality. These harmful environmental impacts are exacerbated in Maize Monoculture (MM) and hasten the need for solutions to overcome the trade off between crop yield and environmental impacts. In a three-year cropping systems experiment, a conventional intensive maize monoculture (MMconv), with a winter bare fallow, deep soil tillage, non-limiting irrigation was compared to three Low Input Cropping Systems (LI-CS) designed as alternatives to the conventional system. They were managed with decision-rules implemented to reach specific objectives of input reduction. The LI-CS designed with Integrated Weed Management (IWM) techniques and other sustainable cropping practices, were:(i) MMLI-an IWM Low Input MM; (ii) MMCT-a Conservation Tillage combined with cover crop MM; and (iii) Maize-MSW-an IWM maize grown in rotation with soybean and wheat. A comprehensive multi criteria assessment was carried out to quantify the agronomic, economic, social, and environmental performances of each system. A canonical discriminant analysis of performance metrics revealed large differences between the four systems. Yields were significantly higher in MMconv (11.0 Mg ha(-1)) and MMLI (10.3 Mg ha(-1)) than in Maize-MSW (8.6 Mg ha(-1)) and MMCT (7.8 Mg ha(-1)). MMCT had the largest weed infestation (density and biomass) despite the greatest use of herbicides. The Herbicide Treatment Frequency Index (HTFI), used to indicate differences in herbicide use, revealed that the MMLI (HTFI = 1.0) and Maize-MSW (1.1) halved the herbicide use as compared to the MMconv (2.1), despite having similar weed abundance levels. The LI-CS, especially MMCT, produced high biomass winter cover crops and then less nitrogen fertilization was required as compared to MMconv. Gross margins in the MMLI (1254 (sic) ha(-1)) and MMconv (1252 (sic) ha(-1)) were higher than the MMCT (637 (sic) ha(-1)) and Maize-MSW (928 (sic) ha(-1)). MMLI and MMconv had similar labour requirements. Water drainage, pesticide leaching, energy use, and estimated greenhouse gas emissions were higher in MMconv than in the LI-CS in most years. Results from this research show good potential for the MMLI to reduce the environmental impacts of MMconv while maintaining its economic and social performance