To investigate the temporal relationship of diabetes-induced renal growth and its associated metabolic alterations to the early development of renal hyperfunction, parallel functional and metabolic studies were performed shortly after the onset of diabetes in rats. Hyperglycemia and hypoinsulinemia were evident 18 h after streptozocin injection, and significant hyperglucagonemia and acidosis were present at 36-48 h. Glomerular filtration rate (GFR), expressed per unit of body weight, first increased at 3 days of diabetes [1.35 ± 0.07 (SE) (N = 14)] and was 18% greater than in controls [1.14 · ± 0.03 ml · min−1 100 g−1 (SE) (N = 38)] (P < .005). Renal enlargement preceded GFR changes, so that GFR per unit of kidney weight was lower at 48 h in diabetics [1.31 ± 0.06 (SE) (N = 16)] than in controls [1.54 ± 0.04 ml · min−1 · g−1 (SE) (N = 38)] (P < .01). Nucleotide and RNA metabolism was studied in the renal cortex after infusion of radiolabeled orotate or adenine. Rate of RNA synthesis, total cellular RNA, and the pools of ATP, UTP, and uridine 5′-diphospho-N-acetyl glucosamine were significantly increased 13–51% in 48-h diabetics. Nucleotide precursor incorporation was significantly increased only in uracil ribonucleotides. The increase in uracil ribonucleotide pool exceeded the degree of cell hypertrophy. Our studies indicate that renal hypertrophy and specific increases in uracil ribonucleotide synthesis precede functional changes in early diabetes. Renal metabolic changes may be the critical primary factors in diabetic nephropathy.
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Original Contributions|
January 01 1987
Relationship Between Renal Function and Metabolic Alterations in Early Streptozocin-Induced Diabetes in Rats
Pedro Cortes;
Pedro Cortes
Department of Medicine, Division of Nephrology and Hypertension, and Richmond W. Smith Research Laboratory, Henry Ford Hospital
, Detroit, Michigan 48202
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Francis Dumler;
Francis Dumler
Department of Medicine, Division of Nephrology and Hypertension, and Richmond W. Smith Research Laboratory, Henry Ford Hospital
, Detroit, Michigan 48202
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Jose Goldman;
Jose Goldman
Department of Medicine, Division of Nephrology and Hypertension, and Richmond W. Smith Research Laboratory, Henry Ford Hospital
, Detroit, Michigan 48202
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Nathan W Levin
Nathan W Levin
Department of Medicine, Division of Nephrology and Hypertension, and Richmond W. Smith Research Laboratory, Henry Ford Hospital
, Detroit, Michigan 48202
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Send correspondence and reprint requests to P. Cortes, M.D., at the above address.
Diabetes 1987;36(1):80–87
Article history
Received:
February 05 1986
Revision Received:
May 09 1986
PubMed:
2431940
Citation
Pedro Cortes, Francis Dumler, Jose Goldman, Nathan W Levin; Relationship Between Renal Function and Metabolic Alterations in Early Streptozocin-Induced Diabetes in Rats. Diabetes 1 January 1987; 36 (1): 80–87. https://doi.org/10.2337/diab.36.1.80
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