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Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance
Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fib...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204312/ https://www.ncbi.nlm.nih.gov/pubmed/27495225 http://dx.doi.org/10.2337/db16-0394 |
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author | Sheikh, Saba Gudipaty, Lalitha De Leon, Diva D. Hadjiliadis, Denis Kubrak, Christina Rosenfeld, Nora K. Nyirjesy, Sarah C. Peleckis, Amy J. Malik, Saloni Stefanovski, Darko Cuchel, Marina Rubenstein, Ronald C. Kelly, Andrea Rickels, Michael R. |
author_facet | Sheikh, Saba Gudipaty, Lalitha De Leon, Diva D. Hadjiliadis, Denis Kubrak, Christina Rosenfeld, Nora K. Nyirjesy, Sarah C. Peleckis, Amy J. Malik, Saloni Stefanovski, Darko Cuchel, Marina Rubenstein, Ronald C. Kelly, Andrea Rickels, Michael R. |
author_sort | Sheikh, Saba |
collection | PubMed |
description | Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite “normal” glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. |
format | Online Article Text |
id | pubmed-5204312 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-52043122018-01-01 Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance Sheikh, Saba Gudipaty, Lalitha De Leon, Diva D. Hadjiliadis, Denis Kubrak, Christina Rosenfeld, Nora K. Nyirjesy, Sarah C. Peleckis, Amy J. Malik, Saloni Stefanovski, Darko Cuchel, Marina Rubenstein, Ronald C. Kelly, Andrea Rickels, Michael R. Diabetes Pathophysiology Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite “normal” glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF. American Diabetes Association 2017-01 2016-08-05 /pmc/articles/PMC5204312/ /pubmed/27495225 http://dx.doi.org/10.2337/db16-0394 Text en © 2017 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. |
spellingShingle | Pathophysiology Sheikh, Saba Gudipaty, Lalitha De Leon, Diva D. Hadjiliadis, Denis Kubrak, Christina Rosenfeld, Nora K. Nyirjesy, Sarah C. Peleckis, Amy J. Malik, Saloni Stefanovski, Darko Cuchel, Marina Rubenstein, Ronald C. Kelly, Andrea Rickels, Michael R. Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title | Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title_full | Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title_fullStr | Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title_full_unstemmed | Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title_short | Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance |
title_sort | reduced β-cell secretory capacity in pancreatic-insufficient, but not pancreatic-sufficient, cystic fibrosis despite normal glucose tolerance |
topic | Pathophysiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5204312/ https://www.ncbi.nlm.nih.gov/pubmed/27495225 http://dx.doi.org/10.2337/db16-0394 |
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