**Abbreviations**

understood. These agents have the clear advantages of being orally available and well tolerated. Salsalate has been shown to improve insulin sensitivity and production, increase secretion of the anti-inflammatory cytokine adiponectin, reduce blood glucose and C-reactive

From our own studies we have shown how different amino and fatty acid combinations may affect β-cell metabolism. This proposes the concept of diet manipulation as an additional treatment for hyperglycaemia and lipidaemia in T2 and even T1DM patients. We demonstrat‐ ed the antioxidant activities of arachidonic acid, arginine and glutamine, and this data may suggests that dietary supplementation, high in specific amino or fatty acids, may have favourable effects in DM patients. Given the role of ROS and ER stress in β-cell death, dietary or pharmacological agents that target these pathways may also represent novel treatments for

Over-nutrition and diminished physical activity in the modern lifestyle has led to a staggering increase in T2DM onset in Western cultures [108]. However, the epidemic is also progressing into the developing world, indicating that T2DM has become a major global health issue [108]. Since the 1990's, T1DM has more than doubled in number and is expected to double again before 2020 [108,148]. The traditional classification of distinct criteria for T1 and T2DM syndromes has become blurred due to the global increase in obese individuals and the incidence of obesity-related insulin-resistance [108]. Currently the paradigm of T1 and T2DM treatment appears to be changing in line with the clarification of dysfunctional pathways that are common to both disease types. Although diet-and-exercise still remains the most effective (and cheapest) treatment, new therapies will be required going into the future. Consequently, an increased understanding of the molecular and biochemical mechanisms that lead to disease

In this manuscript, we have examined some of the key pathways that are essential in the pathogenesis of both T1 and T2DM, and we have reviewed some of the novel treatments that are currently being developed to counteract these dysfunctional processes. It is clear that inflammation, generation of ROS/RNS and ER stress leads to significant damage to pancreatic β-cells, culminating in cell dysfunction, and ultimately cell death. It is hoped that further study of the NFκB and the ER stress-mediated pathways, will reveal novel therapeutic targets that can be developed into a new generation of anti-diabetic treatments, that will improve β-cell

The authors would like to thank Mr. Peter McEvoy for assistance with design and illustration

protein (CRP) and decrease fatty acid and triglyceride levels [90].

the delay or prevention of DM.

150 Type 1 Diabetes

**11. Conclusions and perspectives**

onset and progression are mandatory.

**Acknowledgements**

of Figure 5.

function, survival and regeneration in T1 and T2DM.


**References**

1019-32.

451-63.

[1] Chan, S. J, & Steiner, D. F. Insulin Through the Ages: Phylogeny of a growth promot‐ ing and metabolic regulatory hormone. American Zoologist (2000). , 40, 213-22.

The Impact of Inflammation on Pancreatic β-Cell Metabolism, Function and Failure in T1DM and T2DM…

http://dx.doi.org/10.5772/55349

153

[2] Irwin, D. M, Humer, O, & Youson, J. H. Lamprey Proglucagon and the origin of glu‐ cagon-like peptides. Molecular Biology and Evolution (1999). , 16(11), 1548-57.

[3] Newsholme, P, Abdulkader, F, Rebelato, E, Romanatto, T, Pinheiro, C. H, Vitzel, K. F, Silva, E. P, Bazotte, R. B, Procopio, J, Curi, R, Gorjao, R, & Pithon-curi, T. C. Amino acids and diabetes: implications for endocrine, metabolic and immune functions.

[4] Jitrapakdee, S, Wutthisathapornchai, A, Wallace, J. C, & MacDonald, M.J. Regulation of insulin secretion: role of mitochondrial signalling. Diabetologia (2010). , 53(6),

[5] Rutter, G. A, & Hill, E. V. Insulin vesicle release: walk, kiss, pause…then run. Physi‐

[6] Gembal, M, Gilon, P, & Henquin, J. C. Evidence that glucose can control insulin re‐ lease independently from its action on ATP-sensitive K+ channels in mouse B cells.

[7] Remedi, M. S, Rocheleau, J. V, Tong, A, Patton, B. L, Mcdaniel, M. L, Piston, D. W, Koster, J. C, & Nichols, C. G. Hyperinsulinism in mice with heterozygous loss of

[8] Miki, T, Nagashima, K, Tashiro, F, Kotake, K, Yoshitomi, H, Tammamoto, A, Gonoi, T, Iwanaga, T, Miyazaki, J. I, & Seino, S. Defective insulin secretion and enhanced in‐ sulin action in KATP channel-deficient mice. Proceedings of the National Academy

[9] Straub, S. G, & Sharp, G. W. G. Glucose-stimulated signalling pathways in biphasic insulin secretion. Diabetes and Metabolism Research and Reviews (2002). , 18(6),

[10] Newsholme, P, & Krause, M. Nutritional Regulation of Insulin Secretion: Implica‐

[11] Newsholme, P, Bender, K, Kiely, A, & Brennan, L. Amino acid metabolism, insulin secretion and diabetes. The Biochemical Society Transactions (2007). Pt 5): 1180-6. [12] Opara, E. C, Garfinkel, M, Hubbard, V. S, Burch, W. M, & Akwari, O. E. Effect of fat‐ ty acids on insulin release; role of chain length and degree of unsaturation. The

[13] Keane, D. C, Takahashi, H. K, Dhayal, S, Morgan, N. G, Curi, R, & Newsholme, P. Arachidonic acid actions on functional integrity and attenuation of the negative ef‐

tions for Diabetes. The Clinical Biochemist Reviews (2012). , 33(2), 35-47.

Frontiers in Bioscience (2011). , 16, 315-39.

ology (Bethesda, Md.) (2006). , 21, 189-96.

of Sciences (1998). , 95, 10402-06.

Journal of Clinical Investigations (1992). , 89(4), 1288-95.

K(ATP) channels. Diabetologia (2006). , 49(10), 2368-78.

American Journal of Physiology (1994). Pt 1): E, 635-9.

