INCREASED CLEARANCE OF 1,25(OH)2D3 AND TISSUE-SPECIFIC RESPONSIVENESSTO 1,25(OH)2D3 IN DIABETIC RATS

The kinetics of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the in vivo response to 1,25(OH)2D3 (7.5, 15, and 30 ng/100 g body wt), infused o r injected subcutaneously for 12-14 days, were studied in male spontan eously diabetic and control BB rats. In control rats, increasing doses of 1,25(OH)2D3 produced parallel increases in plasma 1,25(OH)2D3 and calcium, urinary calcium, duodenal CaBP9K, and renal CaBP28K. 1,25(OH) 2D3 at 30 ng/100 g markedly raised plasma osteocalcin and osteoblast/o steoid surfaces in the tibial metaphysis, but inhibited bone mineraliz ation rate. In diabetic rats, plasma 1,25(OH)2D3 concentrations were d ecreased, and the rise of plasma 1,25(OH)2D3 during 1,25(OH)2D3 infusi on was blunted, but the free 1,25(OH)2D3 index remained normal or abov e normal. Diabetic rats had an increased metabolic clearance rate of 1 ,25(OH)2D3 (0.38 +/- 0.015 vs. 0.24 +/- 0.007 ml . min-1 . kg- 1), wit h no further increase in 1,25(OH)2D3-infused diabetic rats; their rela tive production rate of 1,25(OH)2D3 Was unchanged. The responses of pl asma and urinary calcium, duodenal CaBP9K, and renal CaBP28K to infuse d 1,25(OH)2D3 were normal, as was duodenal calcium absorption in 1,25( OH)2D3-injected diabetic rats. However, the virtual absence of osteobl asts/osteoid in trabecular bone was unaltered in diabetic rats infused with 30 ng/100 g 1,25(OH)2D3, with only minimal increase of their low plasma osteocalcin levels. 1,25(OH)2D3 treatment therefore cannot be expected to reverse diabetic osteopenia.