Nickel chloride-induced metabolic changes in the rat and guinea pig

Abstract

This study was undertaken to explore the toxic effects of nickel chloride (NiCl 2) on body metabolism and to elucidate the mechanism of action involved. Nickel chloride was given by various routes: intraperitoneal (8 mg Ni/kg), intratracheal (1 mg Ni), and by long-term ingestion (drinking water, 225 ppm). In addition, an intragastric [ 14C]glucose load (600 mg) was also given to some of the intratracheally injected animals. The following parameters were measured in the serum to assess the effect of Ni on metabolism: total 14C radioactivity, glucose, insulin, total lipids, cholesterol, and triglycerides. Liver glycogen and glucose-6-phosphatase activity was measured to determine glucose turnover in the liver. 63Ni tissue distribution and excretion of 63Ni, calcium, sodium, potassium, zinc, and glucose were also measured as a determination of metal and carbohydrate metabolism, A single intraperitoneal or intratracheal injection of Ni to rats caused a rapid transient increase in serum glucose, but a decrease in serum insulin and glucosuria. When exogenous insulin was given at the same time as the nickel challenge, the elevation of serum glucose was prevented. Glucose turnover studies indicated that the mechanism of action of nickel appears to be in the inhibition of insulin release. This inhibition of insulin release could be related to the extremely high concentration of nickel found in the pituitary and the effect of nickel on the secretion of the pituitary hormones (GH and ACTH).