VITAMIN-D-3 DEFICIENCY AND ALTERATIONS OF GLUCOSE-METABOLISM IN RAT ENDOCRINE PANCREAS

After 5 weeks of vitamin D-3 deficiency, rats exhibited signs of rachi tism, hypocalcaemia and hypoinsulinaemia: As the glucose-induced insul in release process requires calcium and energy production from glucose metabolism within beta cells of Langerhans islets, several steps in t he glycolytic pathway and the tricarboxylic acid cycle within beta cel ls were investigated in vitro. The sensitivity of islets to glucose wa s studied during incubations in the presence of crescent concentration s of glucose (4.2 to 16.7 mM). Comparison of 50% maximal insulin respo nse showed no modifications induced by vitamin D-3 deficiency despite a large fall in the secretory capacity of beta cells. The use of two s ecretagogues (D-glucose and D-glyceraldehyde) to stimulate insulin rel ease at two different glycolysis steps gave similar responses during p erifusions performed in the presence of crescent concentrations of the se nutrients, indicating that vitamin D-3 deficiency was not a major i nfluence on the first steps in glycolysis. Glucose utilisation by isle ts, as determined by (HOH)-H-3 production from D-[5-H-3]glucose, was s lightly decreased during glucose stimulation of islets from vitamin D- 3-deficient rats, whereas glucose oxidation inside the tricarboxylic a cid cycle, as measured by (CO2)-C-14, production from D-[6-C-14]glucos e, was severely affected. These data, which suggest that vitamin D-3 d eficiency affects the glycolytic pathway after the D-glyceraldehyde st ep and mainly alters oxidative events within the tricarboxylic acid cy cle, support the hypothesis of an alteration of mitochondrial metaboli sm.