Neutral red changes arginine-induced glucagon and insulin response in the rat

Rats were treated with neutral red (amino-dimethyl-amino-toluaminozine hydrochloride, NR) twice weekly, 5 ml/kg b.wt.-1 of a 2% solution, for five weeks in order to investigate damage to pancreatic A-cells. After 1-5 weeks of treatment plasma glucagon levels were increased to about two times control values. Plasma glucose was maintained at control values. Following arginine stimulation, 8 micrograms intravenously 100 g b.wt.-1 min.-1 for 30 min., plasma glucagon and insulin concentrations increased 10-fold in normal rats. After NR treatment for 1 and 2 weeks the arginine induced glucagon response was reduced to a two-fold increase, after 5 weeks NR treatment arginine again increased glucagon concentrations 10-fold. There was no change in the 10-fold increase of insulin concentrations from arginine infusion during the NR treatment. Immunohistochemical examination of pancreas demonstrated unchanged number and size of Langerhans' islets. The insulin immunoreactivity of the B-cells appeared constant 0-5 weeks during NR treatment, while glucagon immunoreactivity appeared to lower in the A-cells from animals treated for one or two weeks with NR. After three to five weeks of NR treatment, pancreatic glucagon immunoreactivity appeared restored. We conclude that NR leads to a release of glucagon from pancreatic A-cells, with subsequent hyperglucagonaemia, maintained during repeated administrations. Such repeated administrations lead to a transient "glucagon insufficiency" on top of the hyperglucagonaemia, consisting of restricted ability to further release of glucagon, presumably because of pancreatic A-cell glucagon depletion.