Journal article
Quantifying insulin sensitivity and entero-insular responsiveness to hyper- and hypoglycemia in ferrets
PloS one, Vol.9(3), pp.e90519-e90519
2014
DOI: 10.1371/journal.pone.0090519
PMCID: PMC3940889
PMID: 24594704
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.
Details
- Title: Subtitle
- Quantifying insulin sensitivity and entero-insular responsiveness to hyper- and hypoglycemia in ferrets
- Creators
- Yaling Yi - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaHongshu Sui - 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, ChinaBo Liang - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaXingshen Sun - Department of Anatomy and Cell Biology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaJianrong Yao - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaShanming Hu - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaAliye Uc - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaKatie Larson Ode - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaJohn F Engelhardt - 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 AmericaDeborah J Nelson - Department of Neurobiology, Pharmacology & Physiology, University of Chicago, Chicago, Illinois, United States of AmericaAndrew W Norris - 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 AmericaLouis H Philipson - Department of Medicine, University of Chicago, Chicago, Illinois, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(3), pp.e90519-e90519
- DOI
- 10.1371/journal.pone.0090519
- PMID
- 24594704
- PMCID
- PMC3940889
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library of Science; United States
- Grant note
- R24 HL123482 / NHLBI NIH HHS R01 DK097820 / NIDDK NIH HHS R24 DK096518 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS P30 DK020595 / NIDDK NIH HHS DK54759 / NIDDK NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984024507402771
Metrics
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