Effect of manganese deficiency on insulin secretion and carbohydrate homeostasis in rats

The effects of manganese (Mn) deficiency on carbohydrate metabolism in the Sprague-Dawley rat were investigated. Oral glucose tolerance tests were performed on offspring from Mn-sufficient females rats fed 45 μg Mn per gram diet (C-C), offspring from Mn-deficient female rats fed 1 μg Mn per gram diet (DI-DI) and rats not exposed to Mn deficiency in utero but fed DI diet from weaning to maturity (DI). Mn-deficient rats, DI and DI-DI, had significantly lower concentrations of Mn in liver, kidney, heart and pancreas than controls. DI-DI rats responded with a diabetic type of glucose tolerance curve when given oral glucose. Insulin levels of DI-DI rats were not commensurate with their high glucose levels. Measurements made by using an isolated perfused-pancreas preparation indicate that insulin output due to release of steroid hormone was 76% of control levels in DI-DI rats. This suggests either lower insulin stores or impaired release of insulin in DI-DI rats. Second phase insulin release was also significantly lower in DI-DI rats than in controls. Pancreatic insulin content was 63% of control levels in DI-DI rats, further supporting the idea of lower insulin stores in Mn-deficient rats. No differences in plasma glucose levels were observed between DI rats and controls after an oral-glucose load. These findings indicate that dietary Mn-deficiecy can result in impaired insulin secretion producing impaired carbohydrate metabolism; however, the timing of the deficiency may be a critical factor in the expression of this abnormality.