Effects of in vivo and in vitro insulin on renal 25 (OH) D3 hydroxylation in insulin dependent diabetic rats.
Renal production of 1,25(OH)2D3 and 24,25(OH)2D3 was assessed in proximal tubules derived from two distinct rat models of insulin dependent diabetes. In both streptozotocin (STZ) induced and spontaneously diabetic BB rats, low plasma 1,25(OH)2D3 was associated with comparable decreases in in vitro 1,25(OH)2D3 synthesis. Diabetes was also associated with reduced in vitro 24,25(OH)2D3 synthesis in proximal tubules, suggesting that impaired 1,25(OH)2D3 synthesis was not secondary to enhanced 24-hydroxylase activity resulting in shunting of 25(OH)D3 towards 24,25(OH)2D3 or enhanced conversion of 1,25(OH)2D3 to 1,24,25(OH)3D3. Plasma 1,25(OH)2D3 and impaired 1,25(OH)2D3 synthesis were normalized in STZ diabetic rats within three days of exogenous insulin therapy. In contrast, preincubation for up to 18 hours with insulin did not significantly increase 1,25(OH)2D3 synthesis in proximal tubules from diabetic or control animals, suggesting that either insulin does not directly modulate 1,25(OH)2D3 synthesis, or that insulin acts synergistically with other factors to regulate 1,25(OH)2D3 synthesis in vivo. The correlation between low plasma 1,25(OH)2D3 and impaired 1,25(OH)2D3 production in vitro during diabetes emphasizes the advantages of proximal tubules as a model system for probing interactions between insulin and other modulators of 1-OHASE activity.
Weaver
V M
VM
Department of Biochemistry, University of Ottawa, Ontario, Canada.
Welsh
J E
JE
D000818:Animals; D002112:Calcifediol / Q000378:metabolism*; D002117:Calcitriol / Q000097:blood / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006900:Hydroxylation; D007328:Insulin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008274:Magnesium / Q000097:blood; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012016:Reference Values
D007328:Insulin; D010281:Parathyroid Hormone; D010758:Phosphorus; D002117:Calcitriol; D008274:Magnesium; D002112:Calcifediol; D002118:Calcium