Relationship between calbindin-D28K levels in the A and B cells of the rat endocrine pancreas and the secretion of insulin and glucagon: influence of vitamin D3 deficiency and 1,25-dihydroxyvitamin D3.
The pancreatic B cell is equipped with specific receptors for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and contains vitamin D-dependent calcium binding proteins (calbindin-D). Insulin secretion is impaired by vitamin D deficiency and is restored by 1,25-(OH)2D3 (concomitantly with an improved calcium handling within B cells) but the effect of 1,25-(OH)2D3 on the pancreatic B cell via calbindin-D is unclear. Therefore we examined the relationship between calbindin-D28K or calbindin-D9K and the activity of the endocrine pancreas in normal (N), four week vitamin D-deficient (-D) and one week 1,25-(OH)2D3-replete (+D) rats. Calbindin-D9K was not found in the pancreas, neither in the islets nor in the exocrine part, of any of the groups of rats (N, -D, or+D). Surprisingly, total islet calbindin-D28K content was increased by vitamin D deficiency and partly restored by 1,25-(OH)2D3. Calbindin-D28K immunostaining was observed only on A and B cells in the endocrine part of the pancreas, the greatest staining being found in A cells. This difference in staining density was increased by vitamin D deficiency and decreased by 1,25-(OH)2D3 treatment. In vitro, 1,25-(OH)2D3 also produced a negative influence on calbindin-D28K staining in A cells, as demonstrated using pieces of pancreas incubated with the steroid for 2 h. No significant influence on labeling intensity of B cell calbindin-D28K could be shown. Plasma insulin and islet insulin release in response to 10 mM arginine stimulation were decreased in -D rats and enhanced in +D rats towards N values. In contrast, plasma glucagon and the amount of glucagon secretion, stimulated in vitro by 10 mM arginine or by low (1.7 mM) glucose concentration, was increased in -D rats and attenuated by 1,25-(OH)2D3. Thus there appears to be no relationship between the steady state level of B cell calbindin-D28K and the regulation of insulin secretion by 1,25-(OH)2D3 in vitamin D-deficient rats. However there is a correlation between A cell calbindin-D28K and glucagon secretion, which are both negatively regulated by 1,25-(OH)2D3. The predominance of calbindin-D28K in A cells raises the question as to how A and B cells interact and the role of calbindin-D28K in calcium handling.
Bourlon
P M
PM
Laboratoire Endocrinologie, Université Bordeaux I, Talence, France.
Faure-Dussert
A
A
Billaudel
B
B
Sutter
B C
BC
Tramu
G
G
Thomasset
M
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D064092:Calbindin 1; D064026:Calbindins; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002762:Cholecalciferol / Q000172:deficiency*; D002149:Energy Intake / Q000187:drug effects; D005934:Glucagon / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000032:analysis / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism*
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D007328:Insulin; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D002762:Cholecalciferol; D005934:Glucagon; D001120:Arginine; D002117:Calcitriol