title: A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling.
abstract: 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.
authors: 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.
authors: Yaling
authors: Y
authors: Yi
authors: 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.
authors: Xingshen
authors: X
authors: Sun
authors: 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.
authors: Katherine
authors: K
authors: Gibson-Corley
authors: 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.
authors: Weiliang
authors: W
authors: Xie
authors: 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.
authors: Bo
authors: B
authors: Liang
authors: 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.
authors: Nan
authors: N
authors: He
authors: 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.
authors: Scott R
authors: SR
authors: Tyler
authors: 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.
authors: Aliye
authors: A
authors: Uc
authors: 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.
authors: Louis H
authors: LH
authors: Philipson
authors: 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.
authors: Kai
authors: K
authors: Wang
authors: 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.
authors: Manami
authors: M
authors: Hara
authors: 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.
authors: Katie Larson
authors: KL
authors: Ode
authors: 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.
authors: Andrew W
authors: AW
authors: Norris
authors: 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.
authors: John F
authors: JF
authors: Engelhardt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D005260:Female; D005289:Ferrets; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D018149:Glucose Intolerance / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D007328:Insulin; D005934:Glucagon