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

Yaling Yi; Xingshen Sun; Katherine Gibson-Corley; Weiliang Xie; Bo Liang; Nan He; Scott R Tyler; Aliye Uc; Louis H Philipson; Kai Wang; Manami Hara; Katie Larson Ode; Andrew W Norris; John F Engelhardt

doi:10.1210/en.2015-1935

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

Journal article

Open access

Peer reviewed

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

Yaling Yi, Xingshen Sun, Katherine Gibson-Corley, Weiliang Xie, Bo Liang, Nan He, Scott R Tyler, Aliye Uc, Louis H Philipson, Kai Wang, …

Endocrinology (Philadelphia), Vol.157(5), pp.1852-1865

05/2016

DOI: 10.1210/en.2015-1935

PMCID: PMC4870869

PMID: 26862997

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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.

Glucose Intolerance - metabolism

Glucose Tolerance Test

Cystic Fibrosis - metabolism

Cystic Fibrosis - pathology

Glucagon - genetics

Pancreas - pathology

Male

Glucose Intolerance - pathology

Pancreas - metabolism

Ferrets

Insulin - blood

Hyperglycemia - metabolism

Animals

Insulin Resistance - physiology

Hyperglycemia - pathology

Female

Glucagon - metabolism

Blood Glucose - metabolism

Cytokines - blood

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Title: Subtitle: A Transient Metabolic Recovery from Early Life Glucose Intolerance in Cystic Fibrosis Ferrets Occurs During Pancreatic Remodeling
Creators: Yaling Yi - 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
Xingshen Sun - 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
Katherine Gibson-Corley - 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
Weiliang Xie - 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
Bo Liang - 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
Nan He - 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
Scott R Tyler - 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
Aliye Uc - 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
Louis H Philipson - 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
Kai Wang - 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
Manami Hara - 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
Katie Larson Ode - 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
Andrew W Norris - 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
John F Engelhardt - 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
Resource Type: Journal article
Publication Details: Endocrinology (Philadelphia), Vol.157(5), pp.1852-1865
Publisher: United States
DOI: 10.1210/en.2015-1935
PMID: 26862997
PMCID: PMC4870869
ISSN: 0013-7227
eISSN: 1945-7170
Grant note: R24 HL123482 / NHLBI NIH HHS R01 DK097820 / NIDDK NIH HHS R24 DK096518 / NIDDK NIH HHS U01 DK108334 / NIDDK NIH HHS P30 DK054759 / NIDDK NIH HHS P30 DK020595 / NIDDK NIH HHS
Language: English
Date published: 05/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Endocrinology and Diabetes; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Pathology; Biostatistics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Biochemistry and Molecular Biology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9983997489502771

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