The role of taurine in the pathogenesis of the cardiomyopathy of insulin-dependent diabetes mellitus.
The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology behind diabetic cardiomyopathy, one of the most severe complications of IDDM. Experimental rat models of IDDM exhibit a characteristic increase in tissue levels of taurine in the heart, a change that is not seen in NIDDM rats. This article deals with the causes and possible consequences of this observation which may contribute to the development of diabetic cardiomyopathy. Modulation of pyruvate dehydrogenase (lipoamide) (PDH; EC 1.2.4.1) activity was found to be a possible mode for taurine involvement. PDH is a mitochondrial protein and is the rate-limiting step in the generation of acetyl CoA from glycolysis. In IDDM, PDH activity is decreased through a mechanism that includes the stimulation of the de novo synthesis of a kinase activator protein (KAP) which phosphorylates PDH and inactivates the enzyme. This lesion does not occur in NIDDM rat hearts. Taurine is known to inhibit the phosphorylation of PDH in vitro, and in taurine-depleted rats PDH phosphorylation is known to increase. Thus, the increased levels of taurine in the diabetic heart may be inhibiting this phosphorylation which in turn may be stimulating the synthesis of KAP through a negative feedback process. The main argument for this theory would be the lack of change in both the taurine levels and the activity of PDH in the NIDDM rat model.
Militante
J D
JD
Department of Pharmacology, Texas Tech University, Health Sciences Center, Lubbock 79430, USA.
Lombardini
J B
JB
Schaffer
S W
SW
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D004734:Energy Metabolism; D005246:Feedback; D007527:Isoenzymes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D013654:Taurine / Q000502:physiology*
D007527:Isoenzymes; D011506:Proteins; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D013654:Taurine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases