Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 145

Fig. 16.1 Effect of taurine de fi ciency on glucose tolerance test

16.2.2 Endocrine and Metabolic Defects of MELAS

and Taurine Deficiency

The most important link between the endocrine system and MELAS is diabetes.
According to Vionnet et al. ( 1993 ), 2% of type 2 diabetic patients carry the primary
MELAS-linked tRNA Leu(UUR) mutation. Although enhanced fatty acid metabolism con-
tributes to the development of glucose intolerance in type 2 diabetes, a defect in glucose-
induced insulin secretion by the pancreas can also cause glucose intolerance (Blondel
et al. 1990 ; Maassen et al. 2006 ; Schaffer and Wilson 1993 ). A likely mechanism under-
lying the development of type 2 diabetes in patients with MELAS is a defect in insulin
secretion related to oxidative damage of the pancreatic b-cell (Blondel et al. 1990 ;
Maassen et al. 2004 ). When diabetes is superimposed on MELAS, the metabolic state of
several tissues is altered. While diabetes is associated with reduced glucose metabolism
and elevated fatty acid metabolism, in the nondiabetic MELAS patient energy production
is dominated by anaerobic metabolism (Arakawa et al. 2010 ). Besides the decline in
respiratory chain flux, MELAS is also associated with declines in citric acid cycle flux
and fatty acid oxidation, as well as an increase in the NADH/NAD + ratio that results in
enhanced lactate production culminating in lactic acidosis.
Hansen ( 2001 ) proposed that taurine depletion might potentiate the complications
of diabetes through elevations in protein glycation, reduced osmotic control, endothe-
lial dysfunction, impaired neutrophil function, and enhanced platelet aggregation.
Because diabetes is considered a disease of oxidative stress, one would predict that
reductions in taurine, which is an antioxidant, should potentiate the severity of diabetic
complications. Taurine depletion might also increase the risk of pancreatic damage
(Chang 2000 ). However, based on glucose tolerance tests of 3-month-old female tau-
rine transporter knockout mice, there is no evidence of diabetes (Fig. 16.1 ). Nonetheless,