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**13** 

*1,2,3Brazil 4Ireland* 

**A Novel L-Arginine/L-Glutamine Coupling** 

Paulo Ivo Homem de Bittencourt Jr.1,2,3 and Philip Newsholme4

*1Department of Physiology, Institute of Basic Health Sciences,* 

*4School of Biomolecular and Biomedical Science and Institute for* 

*Federal University of Rio Grande do Sul* 

*Physical Education, Porto Alegre, RS* 

*2Federal University of Rio Grande do Sul School of* 

*Sport and Health, UCD Dublin, Belfield, Dublin 4* 

*3National Institute of Hormones and Women's Health* 

**Hypothesis: Implications for Type 1 Diabetes** 

L-Arginine is synthesised *in vivo* from L-glutamine, L-glutamate, or L-proline via the intestinal-renal axis (**Fig. 1A**) in humans and most other mammals (Wu et al., 2009). In humans, plasma L-glutamine is the precursor of 80% of plasma L-citrulline while plasma L-citrulline, in turn, is the precursor of 10% of plasma L-arginine (van de Poll et al., 2007). Although the intestine consumes L-glutamine at a high rates, dependent on L-glutamine supply (and production from the skeletal muscle), approximately 13% of L-glutamine taken up by the intestine is converted to L-citrulline, so that quantitatively, L-glutamine is the major precursor for intestinal release of L-citrulline (van de Poll et al., 2007), which can be further converted to L-arginine. These observations highlight the importance of L-arginine/L-glutamine metabolic coupling, especially as L-arginine is one of the most potent secretagogues of insulin from the pancreatic beta cells (Palmer et al., 1976), whereas L-arginine deficiency is associated with insulinopenia and failure to secrete insulin in response to glucose (Spinas et al., 1999). L-Arginine is essential for metabolism and function of multiple body organs, with decreased plasma and cellular levels of L-arginine reported in

Since L-arginine is the precursor of nitric oxide (NO)\*, which serves as a key cell signalling molecule in pancreatic islet -cells, restriction in the availability of L-arginine is likely to

\* **Abbreviations used:** CAT, catalase; GSH, glutathione; GSSG, glutathione disulphide; GSPx, glutathione peroxidase; GSRd, glutathione disulphide reductase; HSP70, 70-kDa member of heat shock protein family; eHSP70, extracellular heat shock protein of 70 kDa; IFN-, interferon-; IB, a member of the inhibitors of nuclear factor B; IKK, inhibitor of B kinase; IL-1, interleukin-1; IL1-ra, IL-1 receptor antagonist; iNOS, inducible nitric oxide synthase; NF-B, a member of nuclear transcription factor B; NO, nitric oxide free radical ( N=O); PPAR-, peroxisome proliferator activated receptor-; RNS, reactive nitrogen species; ROS, reactive oxygen species; SNOG, *S-*nitrosoglutathione; SOD,

**1. Introduction** 

type 2 diabetic subjects (Pieper & Dondlinger, 1997).

Alpha Kinase Is Required for the Development of the Skeletal System, Postnatal Growth, and the Function and Viability of the Pancreas. *Mol Cell Biol,* Vol. 22, No.11, (Jun), pp.(3864-3874), 0270-7306

