The effects of a vitamin D deficiency on insulin and glucagon release was determined in the isolated perfused rat pancreas by radioimmunoassay of the secreted proteins. During a 30-minute period of perfusion with glucose and arginine, pancreases from vitamin D-deficient rats exhibited a 48 percent reduction in insulin secretion compared to that for pancreases from vitamin D-deficient rats that had been replenished with vitamin D. Vitamin D status had no effect on pancreatic glucagon secretion. This result, along with the previously demonstrated presence in the pancreas of a vitamin D-dependent calcium-binding protein and cytosol receptor for the hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, indicates an important role for vitamin D in the endocrine functioning of the pancreas.
The vitamin D-dependent calcium-binding protein (CaBP) was localized by immunocytochemistry in the rat and human kidney. In both species 80% of the cells lining the distal convoluted tubules contained CaBP. In the connecting segment and the initial collecting tubule of rat kidney, 50% of the cells was positive; in the outer medullary collecting duct only 15% was positive. In the human kidney, collecting ducts in medullary rays contained 50% positive cells, whereas in the rest of the medulla no positive cells were found. The CaBP-positive cells were identified as principal or clear cells by immunoelectron-microscopy, using the protein A-gold technique. Mitochondria-rich dark cells were negative. In principal cells, CaBP immunoreactive sites were found throughout the cytosol and the nuclear euchromatin. No preferential labeling of cellular membranes was found. The data show that CaBP-positive cells are present in tubular regions that are important in regulating the final excretion of calcium. However, the subcellular distribution of CaBP does not suggest a role in the initial transmembrane transport of Ca2+ but rather indicates an involvement in processes regulating intracellular calcium.
The vitamin D-dependent calcium binding protein (CaBP) of chick duodenum has been localized by immunocytochemistry and by radioimmunoassay. Light microscopically, CaBP was seen to be present in the absorptive cells of the villi while in other cell types of the villi and the crypts, including goblet cells and endocrine cells, no CaBP was seen. At the electron microscopic level, CaBP was shown to be localized in the cytosol and the euchromatin of the nucleus but not in membrane-bounded cytoplasmic compartments. Quantitative evaluation of the immunocytochemical protein A-gold label showed that the terminal web and the cytosol of basal cellular regions were most highly labeled while the brush border was weakly labeled. The radioimmunoassay evaluation of intestinal subcellular fractions indicated that 96% of the homogenate CaBP is in the cytosol high-speed supernatant fraction. Collectively, these results support the hypothesis that the vitamin D-dependent intestinal CaBP may play a role in either regulation of intracellular calcium concentration or movement of calcium across the epithelial cell, rather than directly in the initial step(s) of calcium absorption across the brush border membrane from the gut lumen.The intestinal absorption of calcium is dependent upon continuous access to vitamin D (calciferol) and its daughter metabolite 1,25-dihydroxyvitamin D3 [1,25-(OH)2Da] (29). 1,25-(OH)2Da functions in a fashion analogous to that of classic steroid hormones to induce the biosynthesis of cellular components essential for an efficient calcium translocation process, including a calcium binding protein (CaBP, references 40,43,44). The steady-state level of intestinal CaBP is known to be affected by the dietary level of calcium and phosphorus (17). There is a good correlation between the absolute level of CaBP (l-3% of the soluble cellular protein) and both the occupancy of the intestinal 1,25(OH)2D3 receptors (2, 20) and the stimulation of intestinal calcium transport (24, 37).Thus, there is little doubt that the vitamin D-dependent intestinal CaBP is associated with intestinal calcium uptake (28, 29) but the mechanism of its action at the cellular and molecular level and its localization within the intestinal mucosa are controversial. It has been suggested by Taylor and Wasserman (42) that CaBP is produced in goblet cells and located in the brush border of the absorptive columnar cells while others (1,21,25,26) have found it to be present inside the absorptive columnar cells.This controversy surrounding the localization and role of the
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