Role of Glutamine in the Pathogenesis of Type Diabetes

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Since glutamine appears to act to promote lymphocyte activity, it has been proposed that increased availability of glutamine could play a role in the patho-genesis of some autoimmune conditions, such as type 1 diabetes (Wu et al., 1991). Indeed, the administration of the anti-glutamine-utilization drug acivicin delayed or stopped the progression of the disease in diabetes-prone rats (Misra et al., 1996). Addition of the glutaminase inhibitor 6-diazo-5-oxo-norleucine to macrophages before exposure to rat pancreatic p cells in vitro virtually abolished the lytic capacity of the macrophage towards the target p cells (Murphy and Newsholme, 1999). The glutamine concentration in the plasma of moderately ketoacidotic diabetics at diagnosis is significantly elevated compared with that of age- and sex-matched normal control individuals (P Newsholme, unpublished observations), adding further weight to the argument that this amino acid is important to the pathogenic process.

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