The Study of D-Lactate in Diabetic Rat Kidney

• Main Authors: Liao Tzu-Hsin, 廖紫歆
• Other Authors: Lee Jen-Ai
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/61475852647178380148

碩士 === 臺北醫學大學 === 藥學系 === 91 === Abstract Renal gluconeogenesis has been stressed in diabetes mellitus, as excess glucose is released into the circulation and hyperglycemia is intensified. The main gluconeogenic precursor in kidney is thought to be lactate; however, less is emphasized enantiomerically. L-lactate is a glycolysis end-product, but D-lactate is formed after detoxification of methylglyoxal, which is the main source of advanced glycation end-products. For investigating the complete metabolism and the physiological role of D-lactate, we measured D-lactate levels in normal and diabetic rat kidney homogenates by our established column-switching HPLC method with fluorescence detection. The influence of D-lactate on gluconeogenesis was also estimated by determining the glucose concentrations in D- or L-lactate added in kidney homogenates. Furthermore, the relation between D-lactate and free radicals was determined by cytochrome c with a UV spectrophotometer at 550 nm. This study indicated that D-lactate concentrations in rat kidney were significantly and time-dependently accumulated in diabetic groups after induced for 1, 2, 3, 4 months (2.99, 13.11, 18.19, 23.23 mol/mg, respectively), as comparing that in normal groups (0.79 mol/mg). In addition, the histology of induced 3-month diabetic rat renal showed some structural changes of progressive diabetic nephropathy. Moreover, 80% of glucose released by addition of 6.0 mM of L-lactate (17.24 g/ml) was suppressed when 6.0 mM of D-lactate (3.47 g/ml) was supplied into rat kidney homogenates. It was supposed that D-lactate inhibited gluconeogenesis as an antagonist of L-lactate in rat kidney. On the other hand, the accumulation of D-lactate maybe damage the renal by generating the reactive oxygen species, in which it was determined by cytochrome c with external 6.0 mM D-lactate in rat kidney homogenates.