Effect of α-Ketobutyrate on Microvascular Thickness in the Diabetic Rat Kidney

Abstract

The first objective of this study was to examine the intermediary metabolism of plasma amino acids and keto acids in streptozotocin (STZ)-treated rats. Plasma alpha-aminobutyrate (alpha-ABA) concentration in STZ rats was 1.5-fold greater than in control (CNT) animals at 1 month. In contrast, the level of plasma alpha-ketobutyrate (KB), which is transaminated to alpha-ABA, did not differ significantly between STZ and CNTs at 1 month, and also increased with age. Additionally, HPLC analysis revealed consistent profiles containing peaks of unknown origin. Two pathways exist for the formation of alpha-KB, either from the action of threonine dehydratase or via homocysteine, the latter metabolite being closely associated with the development of cardiovascular disease. These observations suggest that uncharacterized metabolites, including plasma alpha-KB, may be potential risk factors for the development of diabetic complications. We carried out preparatory experiments on non-diabetic rats to investigate the influence of alpha-KB and confirmed this metabolite had no adverse effects. The second aim of the study was to compare vascular wall thickness in diabetic rats treated or untreated with alpha-KB with CNT animals in order to determine the effects of alpha-KB on the renal microvasculature. The thickness of the medial wall of arterioles and small arteries differed significantly among all groups and was increased, especially in the small arterial walls of the diabetic rats treated with alpha-KB. Plasma renin activities (PRA) in both diabetic rats treated or untreated with alpha-KB were decreased significantly compared to CNT animals, while diabetic rats treated with alpha-KB had higher angiotensin converting enzyme (ACE) activity than the CNT group (p < 0.01). These results suggest that alpha-KB may have a role in the renal microvascular complications of diabetes.