Effects of diabetes mellitus on parathyroid hormone-stimulated protein kinase activity, ferredoxin phosphorylation, and renal 1,25-dihydroxyvitamin D production.
Impairment in the stimulation of renal production of 1,25-dihydroxyvitamin D[1,25 (OH)2D] by parathyroid hormone (PTH) occurs in diabetes. Renal response to PTH in terms of 25-hydroxyvitamin D-1-hydroxylase (1-OHase) stimulation involves increased cyclic adenosine monophosphate (cAMP) production, increased cAMP-dependent protein kinase activity, and dephosphorylation of renal ferredoxin (renoredoxin). To identify the step where diabetes might impair PTH stimulation of 1-OHase, we studied the effects of PTH on 1,25(OH)2D production, cAMP content, cAMP-dependent protein kinase activity, and the phosphorylation state of renoredoxin by using renal slices from diabetic and nondiabetic rats. PTH and forskolin significantly stimulated 1,25(OH)2D production in renal slices from nondiabetic animals but not from diabetic animals. PTH-stimulated cAMP production and cAMP-dependent protein kinase activity in renal slices were not altered by diabetes. However, diabetes significantly impaired the capacity of PTH to dephosphorylate renoredoxin and to increase the activity of the 1-OHase enzyme complex. These results suggest that the decreased capacity of PTH to stimulate 1-OHase activity in diabetic animals may reflect the decreased capacity of PTH to alter the phosphorylation state of renoredoxin in these animals.
Wongsurawat
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Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, St. Louis, MO 63125.
Armbrecht
H J
HJ
Siegel
N A
NA
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000032:analysis; D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis*; D005576:Colforsin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005288:Ferredoxins / Q000378:metabolism*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D013311:Streptozocin / Q000633:toxicity
D005288:Ferredoxins; D010281:Parathyroid Hormone; D005576:Colforsin; D013311:Streptozocin; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D011494:Protein Kinases; D002117:Calcitriol