title: Quantifying insulin sensitivity and entero-insular responsiveness to hyper- and hypoglycemia in ferrets.
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.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America; Department of Histology and Embryology, Taishan Medical University, Taian Shandong, China.
authors.forename: Hongshu
authors.initials: H
authors.lastname: Sui
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Yaling
authors.initials: Y
authors.lastname: Yi
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Xingshen
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Shanming
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Aliye
authors.initials: A
authors.lastname: Uc
authors.affiliation: Department of Neurobiology, Pharmacology & Physiology, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Nelson
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Katie Larson
authors.initials: KL
authors.lastname: Ode
authors.affiliation: Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: John F
authors.initials: JF
authors.lastname: Engelhardt
authors.affiliation: Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America; Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Norris
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003920:Diabetes Mellitus / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005289:Ferrets / Q000378:metabolism*; D015309:Glucose Clamp Technique / Q000379:methods*; D006943:Hyperglycemia / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology
chemical_list: D054795:Incretins; D007328:Insulin; D007530:Isoflurane