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PLoS One. 2014 Mar 3;9(3):e90519. doi: 10.1371/journal.pone.0090519. eCollection 2014.

Quantifying insulin sensitivity and entero-insular responsiveness to hyper- and hypoglycemia in ferrets.

Author information

  • 1Department 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.
  • 2Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
  • 3Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.
  • 4Department of Neurobiology, Pharmacology & Physiology, University of Chicago, Chicago, Illinois, United States of America.
  • 5Department of Medicine, University of Chicago, Chicago, Illinois, United States of America.
  • 6Department 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.
  • 7Department 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.

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.

PMID:
24594704
[PubMed - indexed for MEDLINE]
PMCID:
PMC3940889
Free PMC Article
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