Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass

Aliye Uc; Alicia K Olivier; Michelle A Griffin; David K Meyerholz; Jianrong Yao; Maisam Abu-El-Haija; Katherine M Buchanan; Oriana G Vanegas Calderón; Marwa Abu-El-Haija; Alejandro A Pezzulo; Leah R Reznikov; Mark J Hoegger; Michael V Rector; Lynda S Ostedgaard; Peter J Taft; Nick D Gansemer; Paula S Ludwig; Emma E Hornick; David A Stoltz; Katie L Ode; Michael J Welsh; John F Engelhardt; Andrew W Norris

doi:10.1042/CS20140059

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Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass

Journal article

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Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass

Aliye Uc, Alicia K Olivier, Michelle A Griffin, David K Meyerholz, Jianrong Yao, Maisam Abu-El-Haija, Katherine M Buchanan, Oriana G Vanegas Calderón, Marwa Abu-El-Haija, Alejandro A Pezzulo, …

Clinical science (1979), Vol.128(2), pp.131-142

01/2015

DOI: 10.1042/CS20140059

PMCID: PMC4346161

PMID: 25142104

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https://www.ncbi.nlm.nih.gov/pmc/articles/4346161View

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Abstract

Diabetes is a common and significant co-morbidity in cystic fibrosis (CF). The pathogenesis of cystic fibrosis related diabetes (CFRD) is incompletely understood. Because exocrine pancreatic disease is similar between humans and pigs with CF, the CF pig model has the potential to contribute significantly to the understanding of CFRD pathogenesis. We determined the structure of the endocrine pancreas in fetal, newborn and older CF and non-CF pigs and assessed endocrine pancreas function by intravenous glucose tolerance test (IV-GTT). In fetal pigs, pancreatic insulin and glucagon density was similar between CF and non-CF. In newborn and older pigs, the insulin and glucagon density was unchanged between CF and non-CF per total pancreatic area, but increased per remnant lobular tissue in CF reflecting exocrine pancreatic loss. Although fasting glucose levels were not different between CF and non-CF newborns, CF newborns demonstrated impaired glucose tolerance and increased glucose area under the curve during IV-GTT. Second phase insulin secretion responsiveness was impaired in CF newborn pigs and significantly lower than that observed in non-CF newborns. Older CF pigs had elevated random blood glucose levels compared with non-CF. In summary, glycaemic abnormalities and insulin secretion defects were present in newborn CF pigs and spontaneous hyperglycaemia developed over time. Functional changes in CF pig pancreas were not associated with a decline in islet cell mass. Our results suggest that functional islet abnormalities, independent of structural islet loss, contribute to the early pathogenesis of CFRD.

Diabetes Mellitus - pathology

Glucose Tolerance Test

Islets of Langerhans - physiology

Enzyme-Linked Immunosorbent Assay

Islets of Langerhans - pathology

Cystic Fibrosis - metabolism

Cystic Fibrosis - pathology

Diabetes Mellitus - metabolism

Pancreas - pathology

Blood Glucose

Pancreas - metabolism

Cystic Fibrosis - complications

Insulin - blood

Glucose Intolerance

Insulin - metabolism

Animals

Islets of Langerhans - metabolism

Swine

Insulin Secretion

Details

Title: Subtitle: Glycaemic regulation and insulin secretion are abnormal in cystic fibrosis pigs despite sparing of islet cell mass
Creators: Aliye Uc - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
Alicia K Olivier - †Department of Pathology, University of Iowa, Iowa City, IA, U.S.A
Michelle A Griffin - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
David K Meyerholz - †Department of Pathology, University of Iowa, Iowa City, IA, U.S.A
Jianrong Yao - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
Maisam Abu-El-Haija - ‡Division of Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, U.S.A
Katherine M Buchanan - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
Oriana G Vanegas Calderón - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
Marwa Abu-El-Haija - §University of Texas Medical Branch at Galveston, Galveston, TX, U.S.A
Alejandro A Pezzulo - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Leah R Reznikov - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Mark J Hoegger - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Michael V Rector - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Lynda S Ostedgaard - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Peter J Taft - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Nick D Gansemer - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Paula S Ludwig - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Emma E Hornick - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
David A Stoltz - ∥Department of Internal Medicine, University of Iowa, Iowa City, IA, U.S.A
Katie L Ode - Department of Pediatrics, University of Iowa, Iowa City, IA, U.S.A
Michael J Welsh
John F Engelhardt - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, U.S.A
Andrew W Norris
Resource Type: Journal article
Publication Details: Clinical science (1979), Vol.128(2), pp.131-142
DOI: 10.1042/CS20140059
PMID: 25142104
PMCID: PMC4346161
NLM abbreviation: Clin Sci (Lond)
ISSN: 0143-5221
eISSN: 1470-8736
Publisher: England
Grant note: PPG HL091842 / NHLBI NIH HHS P30 ES005605 / NIEHS NIH HHS R01 DK084049 / NIDDK NIH HHS P01 HL51670 / NHLBI NIH HHS Howard Hughes Medical Institute T32 HL007638 / NHLBI NIH HHS DK097820 / NIDDK NIH HHS T32 GM007337 / NIGMS NIH HHS P30 DK54759 / NIDDK NIH HHS DK084049 / NIDDK NIH HHS S10 RR025439 / NCRR NIH HHS P01 HL091842 / NHLBI NIH HHS R24 DK096518 / NIDDK NIH HHS R21 DK096327 / NIDDK NIH HHS R01 DK097820 / NIDDK NIH HHS P01 HL051670 / NHLBI NIH HHS P30 DK054759 / NIDDK NIH HHS K99 HL119560 / NHLBI NIH HHS
Language: English
Date published: 01/2015
Academic Unit: Neurology; Endocrinology and Diabetes; Microbiology and Immunology; Pathology; Biochemistry and Molecular Biology; Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition; Neurosurgery; Internal Medicine
Record Identifier: 9984013918202771

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