Montgomery T M, Nelson R W, Feldman E C, Robertson K, Polonsky K S
Veterinary Medical Teaching Hospital, Chicago, IL, USA.
J Vet Intern Med. 1996 May-Jun;10(3):116-22. doi: 10.1111/j.1939-1676.1996.tb02042.x.
Serum glucose and plasma C-peptide response to i.v. glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated 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, 10, 20, 30, and (for healthy dogs) 60 minutes after i.v. administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after i.v. 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 i.v. 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 sampling times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .00l) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .01) 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 C-peptide 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 concentrations greater than 2 SD (ie, > 0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with the results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired beta-cell function (ie, diabetes mellitus), and dogs with increased beta-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of beta-cell loss in dogs with type-1 diabetes.
在24只健康犬、12只未经治疗的糖尿病犬、30只接受胰岛素治疗的糖尿病犬和8只自然发生肾上腺皮质功能亢进的犬中，评估了静脉注射胰高血糖素后血清葡萄糖和血浆C肽的反应。除20只接受胰岛素治疗的糖尿病犬外，还对所有犬的血清胰岛素反应进行了评估。在每只犬静脉注射1 mg胰高血糖素之前以及注射后5、10、20、30分钟（对于健康犬，还在60分钟）采集血样，用于测定血清葡萄糖、血清胰岛素和血浆C肽。在健康犬中，胰高血糖素刺激引起的血浆C肽和血清胰岛素浓度变化模式相同，静脉注射胰高血糖素后约15分钟观察到血浆C肽和血清胰岛素浓度出现单峰。未经治疗的糖尿病犬的平均血浆C肽和血清胰岛素浓度，以及接受胰岛素治疗的糖尿病犬的平均血浆C肽浓度在静脉注射胰高血糖素后未显著增加。10只接受胰岛素治疗的糖尿病犬的血清胰岛素浓度结果的有效性存疑，可能是因为抗胰岛素抗体干扰了胰岛素放射免疫测定。与健康犬、未经治疗和接受胰岛素治疗的糖尿病犬相比，肾上腺皮质功能亢进犬在注射胰高血糖素后的所有采血时间点，血浆C肽和血清胰岛素浓度均显著升高（P <.001）。与健康犬相比，糖尿病犬的5分钟C肽增量、C肽峰值反应、总C肽分泌，以及未经治疗的糖尿病犬的胰岛素峰值反应和总胰岛素分泌均显著降低（P <.001），而与健康犬、未经治疗和接受胰岛素治疗的糖尿病犬相比，肾上腺皮质功能亢进犬的这些相同参数均显著升高（P <.01）。尽管无统计学意义，但在胰高血糖素刺激试验期间，未经治疗的糖尿病犬的血浆C肽浓度有高于接受胰岛素治疗的糖尿病犬的趋势。与接受胰岛素治疗超过1年的糖尿病犬相比，接受胰岛素治疗少于6个月的糖尿病犬的基线C肽浓度也显著更高（P <.05）。最后，42只糖尿病犬中有7只的基线血浆C肽浓度高于正常平均血浆C肽浓度2个标准差（即> 0.29 pmol/mL）；与健康犬的结果相比（P <.001）以及与其他35只糖尿病犬相比（P <.001），这些值显著更高。总之，在胰高血糖素刺激试验期间测量血浆C肽浓度有助于区分健康犬、β细胞功能受损的犬（即糖尿病犬）和β细胞对胰高血糖素反应性增加的犬（即胰岛素抵抗犬）。在糖尿病犬中，胰高血糖素刺激试验期间的血浆C肽浓度存在差异，可能代表1型和2型糖尿病犬，或者更可能代表1型糖尿病犬β细胞损失严重程度的差异。
