Send to

Choose Destination
Endocrinology. 2016 May;157(5):1852-65. doi: 10.1210/en.2015-1935. Epub 2016 Feb 10.

A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling.

Author information

Anatomy and Cell Biology (Y.Y., X.S., W.X., B.L., N.H., S.R.T., J.F.E.), Departments of Pathology (K.G.-C.) and Pediatrics (A.U., K.L.O., A.W.N.), Fraternal Order of Eagles Diabetes Research Center (A.W.N., J.F.E.), and Department of Biostatistics (K.W.), College of Public Health, University of Iowa, Iowa City, Iowa 52242; and Department of Medicine (L.H.P., M.H.), University of Chicago, Chicago, Illinois 60637.


Cystic fibrosis (CF)-related diabetes in humans is intimately related to exocrine pancreatic insufficiency, yet little is known about how these 2 disease processes simultaneously evolve in CF. In this context, we examined CF ferrets during the evolution of exocrine pancreatic disease. At 1 month of age, CF ferrets experienced a glycemic crisis with spontaneous diabetic-level hyperglycemia. This occurred during a spike in pancreatic inflammation that was preceded by pancreatic fibrosis and loss of β-cell mass. Surprisingly, there was spontaneous normalization of glucose levels at 2-3 months, with intermediate hyperglycemia thereafter. Mixed meal tolerance was impaired at all ages, but glucose intolerance was not detected until 4 months. Insulin secretion in response to hyperglycemic clamp and to arginine was impaired. Insulin sensitivity, measured by euglycemic hyperinsulinemic clamp, was normal. Pancreatic inflammation rapidly diminished after 2 months of age during a period where β-cell mass rose and gene expression of islet hormones, peroxisome proliferator-activated receptor-γ, and adiponectin increased. We conclude that active CF exocrine pancreatic inflammation adversely affects β-cells but is followed by islet resurgence. We predict that very young humans with CF may experience a transient glycemic crisis and postulate that pancreatic inflammatory to adipogenic remodeling may facilitate islet adaptation in CF.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center