Puberty and Diabetes in the Kidney

Puberty unmasks or accelerates nephropathies, including the nephropathy of diabetes mellitus (DM). A number of cellular systems implicated in the kidney disease of DM interweave, forming an interdependent functional web. We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-β) signaling system would be differentially regulated in male rats depending on the age of onset of DM. Keywords: Age-Disease State Interaction Analysis Male rat littermates began the 6-week-protocol at 4 or 14 weeks of age with injection of streptozocin, 65 mg/kg iv, or equal volume of vehicle. 3 days later insulin palmitate or palmitate vehicle pellets were implanted once hyperglycemia was confirmed. Rats received ad lib food and water for 6 weeks and maintained blood glucose levels 350-350 mg/dl in diabetic groups. Kidneys were removed under isoflurane anesthesia. The cortex was rapidly dissected from the medulla and snap-frozen. Cortex was stored at -80 until all rats had completed the protocol. RNA was isolated from renal cortex and the transcriptome analyzed using gene chips with more than 30,000 transcripts. Age-specific effects of DM were demonstrated for 1,760 transcripts. Analysis then focused on 89 genes involved in the TGF-β signaling pathway.