Although manganese deficiency and manganese toxicity both have pathological consequences, the underlying biochemical lesions have not been well defined. Manganese is involved in carbohydrate metabolism; either deficiency or excess results in abnormal carbohydrate metabolism. Clinical studies have shown that patients with chronic manganism have hypoglycemia following a glucose load. One report has been published of a diabetic patient who responded to oral manganese with a consistent drop in blood glucose. Rats fed a manganese deficient diet respond to an oral glucose load with a diabetic type of glucose tolerance curve. Insulin release from the pancreas of manganese deficient animals in response to a glucose stimulus is lower than controls. Reduced insulin output occurs in both the first phase (release of stored hormone) and second phase (release of stored and newly synthesized hormone) of insulin output. Thus dietary manganese deficiency can result in abnormal insulin production producing impaired carbohydrate metabolism. Manganese toxicity also affects carbohydrate metabolism. Rats given intraperitoneal injections of high levels of manganese show a rapid hyperglycemia and hypoinsulinemia, followed by a reactionary hypoglycemia. The changes in blood glucose and blood insulin levels correlated with changes in liver and pancreatic manganese concentrations, suggesting that some of the effects of manganese on carbohydrate metabolism may be due to a direct effect on insulin release and gluconeogenesis.