Vitamin D3 deficiency and alterations of glucose metabolism in rat endocrine pancreas.
After 5 weeks of vitamin D3 deficiency, rats exhibited signs of rachitism, hypocalcaemia and hypoinsulinaemia. As the glucose-induced insulin release process requires calcium and energy production from glucose metabolism within beta cells of Langerhans islets, several steps in the glycolytic pathway and the tricarboxylic acid cycle within beta cells were investigated in vitro. The sensitivity of islets to glucose was studied during incubations in the presence of crescent concentrations of glucose (4.2 to 16.7 mM). Comparison of 50% maximal insulin response showed no modifications induced by vitamin D3 deficiency despite a large fall in the secretory capacity of beta cells. The use of two secretagogues (D-glucose and D-glyceraldehyde) to stimulate insulin release at two different glycolysis steps gave similar responses during perifusions performed in the presence of crescent concentrations of these nutrients, indicating that vitamin D3 deficiency was not a major influence on the first steps in glycolysis. Glucose utilisation by islets, as determined by 3HOH production from D-[5-3H]glucose, was slightly decreased during glucose stimulation of islets from vitamin D3-deficient rats, whereas glucose oxidation inside the tricarboxylic acid cycle, as measured by 14CO2 production from D-[6-14C]glucose, was severely affected. These data, which suggest that vitamin D3 deficiency affects the glycolytic pathway after the D-glyceraldehyde step and mainly alters oxidative events within the tricarboxylic acid cycle, support the hypothesis of an alteration of mitochondrial metabolism.
Billaudel
B
B
Laboratoire d'Endocrinologie, Université de Bordeaux 1, Talence, France.
Barakat
L
L
Faure-Dussert
A
A
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000097:blood; D002762:Cholecalciferol / Q000172:deficiency; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D006019:Glycolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012279:Rickets / Q000209:etiology / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D002762:Cholecalciferol; D005985:Glyceraldehyde; D005947:Glucose; D002118:Calcium