Serum glucose and plasma C-peptide response t o IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulintreated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,lO. 20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma Cpeptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased ( P < ,001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Fiveminute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin he classification of diabetes mellitus into insulin-depen-T dent (IDDM), non-insulin -dependent (NIDDM), gestational, and subclinical diabetes with impaired glucose tolerance is dependent, in part, on results of insulin secretagogue testing." An IV glucagon tolerance test, with blood samples obtained for measurement of plasma insulin-connecting peptide (C-peptide) concentration prior to and 6 minutes after glucagon administration, is a widely used test of pancreatic &cell function in human^.^ C-peptide is a linear amino acid chain that "connects" the A and B chains of insulin within the proinsulin molecule. Proteolytic cleavage of pro- peak response and total insulin secretion were significantly lower ( P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased ( P < ,011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline Cpeptide concentrations also were significantly higher ( P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concen...
