Nickel-induced hyperglycaemia: the role of insulin and glucagon.
Glucagon and insulin changes were measured in acute nickel-treated rats. Also, several parameters related to glucose homeostasis were evaluated. Nickel treatment caused an important and transitory rise in plasma glucose levels. These changes occurred simultaneously to hyperglucagonemia and hypoinsulinemia, leading to a drastic drop in the insulin/glucagon plasma ratio. In such a catabolic situation, hepatic and muscular glycogen levels remained almost unaltered. Hepatic fructose-2,6-bisphosphate (an indicator of gluconeogenic/glycolytic state) was drastically reduced a short time after nickel injection. Such events suggested that it was mainly gluconeogenesis and not glycogenolysis, which contributes to enhanced plasma glucose. Animals treated with large doses of glucagon did not mimic the hyperglycaemic responses induced by nickel, due to counteracting effects of insulin on plasma glucose. When diabetic rats were treated with nickel, the hyperglucagonemic response still remained, but plasma glucose levels did not increase at the same extent as when nickel was applied to control animals. Overall results suggest that both, glucagon and insulin changes are essential in the development of nickel-induced hyperglycaemia. Also, the lack of glycogenolytic response insinuates a direct or indirect inhibition of this process mediated by nickel and will need further investigation.
Cartañà
J
J
Departament d'Enginyeria Química i Bioquímica, Universitat de Barcelona, Tarragona, Spain.
Arola
L
L
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism / Q000494:pharmacology; D006706:Homeostasis; D006943:Hyperglycemia / Q000139:chemically induced* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; C022838:nickel chloride; D009532:Nickel; D006003:Glycogen; D005934:Glucagon