The mechanism of hypercalciuria in streptozotocin-induced diabetic rats.
Metabolic studies were performed in streptozotocin-induced diabetic (D) rats and normal control (C) rats to assess the role of hyperphagia in the hypercalciuria of diabetes. Urinary calcium excretion (UCaV) was significantly higher in D v C rats fed ad libitum. When D rats were pair-fed (calorie and mineral restriction) with C rats, UCaV declined but remained significantly higher than in C rats. When D rats were allowed their usual increased calorie intake but restricted to C rat mineral consumption, UCaV remained elevated. These findings suggested a tubular reabsorptive defect. In vivo microinjection studies were then performed to identify the site(s) of the tubular reabsorptive defect. Using 1.0 mmol/L Ca in the injectate, 45Ca recovery in the urine (CaR%) was significantly higher in D rats after intratubular injections into early and late proximal tubules and late distal but not early distal tubules. An additional load-dependent defect was revealed in the terminal nephron when the Ca concentration of the injectate was increased to 1.8 mmol/L. After early distal injection, CaR% was significantly increased in D v C rats. Infusion of PTH into thyroparathyroidectomized C and D rats enhanced Ca absorption to a similar degree but did not correct the reabsorptive defect in D rats. These results argue against a lack of end-organ responsiveness to PTH in diabetes or a low serum PTH level as the cause of the hypercalciuria. We conclude that hyperphagia contributes to the hypercalciuria of diabetes in the absence of increased Ca intake. Also, two tubular reabsorptive defects exist: one in the loop of Henle; the other, load-dependent in the terminal nephron.(ABSTRACT TRUNCATED AT 250 WORDS)
Guruprakash
G H
GH
Department of Medicine, Veterans Administration Center, Houston, TX.
Krothapalli
R K
RK
Rouse
D
D
Babino
H
H
Suki
W N
WN
D000042:Absorption; D000818:Animals; D002118:Calcium / Q000652:urine*; D003921:Diabetes Mellitus, Experimental / Q000652:urine*; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D009399:Nephrons / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004040:Dietary Carbohydrates; D010281:Parathyroid Hormone; D002118:Calcium