Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid

BACKGROUND: Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs). However, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. We have previously shown that trivalent metabolites of iAs, arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt). OBJECTIVES: Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs(III) and MAs(III). METHODS: The effects of iAs(III) and MAs(III) on components of the insulin-activated signal transduction pathway that regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes. RESULTS: Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase. Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473) phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed. Notably, expression of constitutively active PKB/Akt restored the normal ISGU pattern in adipocytes treated with either iAs(III) or MAs(III). CONCLUSIONS: These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with human exposures to iAs

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Not AvailableOpen field rice strawburning causes air pollution, GHGs emission (7300 kg CO2-equivalent per hectare), soil nutrient and biodiversity losses and human health hazards. Huge amount (731 million tons (MT)) of rice straw is produced globally in which India contributed around 126.6 MT, and 60% of them are burnt on the field. Once a wealth, the straw now became a waste subjected to burning due to technical, structural, institutional, and socioeconomic challenges. However, straw could be sustainably used to produce bioethanol, biochar, compost, mushroom, fuel-briquette, fuel-pellets, pulp, animal-feed, eco-panel, erosion-control material, and in-situ addition in conservation agriculture. In this review, we elaborated the technical and economic potential of the alternative straw management practices along with their tangible and intangible benefits, primarily on Indian context. The economic and environmental gains and losses of alternate straw management options were estimated. We found that the net gain (both economic and environmental gain) of US$664 per hectare due to production of bioethanol from straw followed by biochar conversion (US$ 183 ha−1), and conservation agriculture (CA) practices (US$131 ha−1). While in Indian context there was a net loss of US$ 107/ha due to burning which includes both environmental (intangible) US$81 ha−1 and economic (tangible) losses US$ 112/ha−1. The estimates indicated the potential gains/losses based on the measured, analyzed, and published data assuming that proper and efficient infrastructure and policy support would be assured during the sustainable management of the straw.Not Availabl