Search

Abstract: Background and aims: Lupin seed is referred to as an antidiabetic product in traditional medicine. Conglutin-γ, a lupin seed glycoprotein, was found to cause a significant plasma glucose reduction when orally administered to rats in glucose overload trials. Conglutin-γ was identified as being responsible for the claimed biological activity, and the aim of this work was to envisage its hypothetical insulin-mimetic cellular mechanism of action. Insulin is responsible for proteosynthesis control through IRS/AKT/P70S6k/PHAS1 pathways modulation, glucose homeostasis through PKC/Flotillin-2/caveolin-3/Cbl activation and muscle differentiation/hypertrophy via muscle-specific MHC gene transcription control. Methods and results: To assess whether conglutin-γ modulates the same insulin-activated kinases, myoblastic C2C12 cells were incubated after 72h of differentiation with 100nM insulin or 0.5mg/mL (∼10μM) conglutin-γ. Metformin-stimulated cells were used as a positive control. The effect on the above mentioned pathways was evaluated after 5, 10, 20 and 30min. In the control cells medium insulin, conglutin-γ and metformin were not added. We demonstrated that insulin or conglutin-γ cell stimulation resulted in the persistent activation of protein synthetic pathway kinases and increased glucose transport, glut4 translocation and muscle-specific gene transcription regulation. Conclusions: Our results indicate that conglutin-γ may regulate muscle energy metabolism, protein synthesis and MHC gene transcription through the modulation of the same insulin signalling pathway, suggesting the potential therapeutic use of this natural legume protein in the treatment of diabetes and other insulin-resistant conditions, as well as the potential conglutin-γ influence on muscle cells differentiation and regulation of muscle growth. [Copyright &y& Elsevier]

Abstract: Background: This study examined the metabolic effects of lung transplantation in patients with end-stage respiratory failure on low dose of steroids for immunosuppressive therapy. Methods: We examined 6 patients, including 2 women and 4 men of overall mean age 53 ± 15 years and age at transplantation 34 ± 12 months, receiving cyclosporine 5.73 ± 1.43 mg/kg/d or tacrolimus (FK 506) 4.67 ± 0.58 mg/d, azathioprine 0.47 ± 0.29 mg/kg/d, and prednisone 8.25 mg/d for comparison with 6 healthy subjects, who were selected to be comparable to the recipients in terms of anthropometric features and age. A euglycemic hyperinsulinemic clamp (1 mU/kg/min) associated with infusion of glucose and leucine isotopes was performed with indirect calorimetry. Results: Lung transplanted patients showed postabsorptive leucine and free fatty acid metabolism similar to controls. In contrast, there was peripheral insulin resistance with respect to glucose metabolism namely, higher values of glucose and insulin vs controls (P < .03 and P < .02, respectively). During the clamp the metabolic picture was characterized by a relative insulin resistance with respect to glucose metabolism (P = .07). Lipid and protein metabolism in the basal and insulin-stimulated conditions were similar to the control group. Conclusions: In the basal condition insulin resistance is evident with respect to glucose metabolism. The metabolic picture in lung transplanted patients on low-dose steroid therapy was characterized by normal insulin-stimulated glucose, leucine, and free fatty acid metabolism. The minimal metabolic alterations in these patients were not due to transplantation itself but probably mainly attributable to immunosuppressive therapy. [Copyright &y& Elsevier]