Abstract
Ferrets are an important emerging model of cystic fibrosis related diabetes. However, there is little documented experience in the use of advanced techniques to quantify aspects of diabetes pathophysiology in the ferret. Glycemic clamps are the gold standard technique to assess both insulin sensitivity and insulin secretion in humans and animal models of diabetes. We therefore sought to develop techniques for glycemic clamps in ferrets. To assess insulin sensitivity, we performed euglycemic hyperinsulinemic clamps in 5–6 week old ferrets in the anesthetized and conscious states. To assess insulin secretion, we performed hyperglycemic clamps in conscious ferrets. To evaluate responsiveness of ferret islet and entero-insular hormones to low glucose, a portion of the hyperglycemic clamps were followed by a hypoglycemic clamp. The euglycemic hyperinsulinemic clamps demonstrated insulin responsiveness in ferrets similar to that previously observed in humans and rats. The anesthetic isoflurane induced marked insulin resistance, whereas lipid emulsion induced mild insulin resistance. In conscious ferrets, glucose appearance was largely suppressed at 4 mU/kg/min insulin infusion, whereas glucose disposal was progressively increased at 4 and 20 mU/kg/min insulin. Hyperglycemic clamp induced first phase insulin secretion. Hypoglycemia induced a rapid diminishment of insulin, as well as a rise in glucagon and pancreatic polypeptide levels. The incretins GLP-1 and GIP were affected minimally by hyperglycemic and hypoglycemic clamp. These techniques will prove useful in better defining the pathophysiology in ferrets with cystic fibrosis related diabetes.
Highlights
Ferrets (Mustela putorius furo) are a domestic mammal
Because data in the cystic fibrosis (CF) ferret model suggests the potential for impaired shutoff of insulin secretion during hypoglycemia [22], we developed a clamp protocol capable of assessing the kinetics of insulin reductions following the transition from a hyperglycemic to a hypoglycemia state
Assessment of Insulin Sensitivity Euglycemic hyperinsulinemic clamps were performed in ferrets to define their insulin sensitivity
Summary
Ferrets (Mustela putorius furo) are a domestic mammal. Ferrets are excellent models of a wide variety of human diseases including influenza, lung disease, cardiovascular disease, and peptic ulcer disease [1]. The sequencing of the ferret genome was completed, rendering the molecular tool-box for ferret research readily accessible. Genetic engineering of ferret models of human disease is possible. We recently described ferrets with targeted knockout of the cystic fibrosis transmembrane conductance regulator (CFTR) gene [2]. Like humans with cystic fibrosis (CF), the CFTR(2/2) ferrets develop severe lung and gastrointestinal disease [3] and serve as a highly relevant model for unraveling CF pathophysiology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
