α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes
Summary: Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compart...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-03-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718302134 |
| _version_ | 1818136328767799296 |
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| author | Marcela Brissova Rachana Haliyur Diane Saunders Shristi Shrestha Chunhua Dai David M. Blodgett Rita Bottino Martha Campbell-Thompson Radhika Aramandla Gregory Poffenberger Jill Lindner Fong Cheng Pan Matthias G. von Herrath Dale L. Greiner Leonard D. Shultz May Sanyoura Louis H. Philipson Mark Atkinson David M. Harlan Shawn E. Levy Nripesh Prasad Roland Stein Alvin C. Powers |
| author_facet | Marcela Brissova Rachana Haliyur Diane Saunders Shristi Shrestha Chunhua Dai David M. Blodgett Rita Bottino Martha Campbell-Thompson Radhika Aramandla Gregory Poffenberger Jill Lindner Fong Cheng Pan Matthias G. von Herrath Dale L. Greiner Leonard D. Shultz May Sanyoura Louis H. Philipson Mark Atkinson David M. Harlan Shawn E. Levy Nripesh Prasad Roland Stein Alvin C. Powers |
| author_sort | Marcela Brissova |
| collection | DOAJ |
| description | Summary: Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia. : Brissova et al. find that β cells in the type 1 diabetic (T1D) pancreas maintain several functional and molecular features, but α cells have impaired glucagon secretion and an altered gene expression profile. These findings provide insight into the mechanism of α cell dysfunction in T1D. Keywords: type 1 diabetes, glucagon, insulin, pancreatic islet, alpha cells, human |
| first_indexed | 2024-12-11T09:38:40Z |
| format | Article |
| id | doaj.art-179fb49bdb1e47cd9d5843dc1eb65012 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T09:38:40Z |
| publishDate | 2018-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-179fb49bdb1e47cd9d5843dc1eb650122022-12-22T01:12:44ZengElsevierCell Reports2211-12472018-03-01221026672676α Cell Function and Gene Expression Are Compromised in Type 1 DiabetesMarcela Brissova0Rachana Haliyur1Diane Saunders2Shristi Shrestha3Chunhua Dai4David M. Blodgett5Rita Bottino6Martha Campbell-Thompson7Radhika Aramandla8Gregory Poffenberger9Jill Lindner10Fong Cheng Pan11Matthias G. von Herrath12Dale L. Greiner13Leonard D. Shultz14May Sanyoura15Louis H. Philipson16Mark Atkinson17David M. Harlan18Shawn E. Levy19Nripesh Prasad20Roland Stein21Alvin C. Powers22Department of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA; Corresponding authorDepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USADepartment of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USAHudsonAlpha Institute for Biotechnology, Huntsville, AL, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USA; Math and Science Division, Babson College, Wellesley, MA 02457, USAInstitute of Cellular Therapeutics, Allegheny-Singer Research Institute, Allegheny Health Network, Pittsburgh, PA, USADepartment of Pathology, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USAType 1 Diabetes Center, the La Jolla Institute for Allergy and Immunology, La Jolla, CA, USADepartment of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USAThe Jackson Laboratory, Bar Harbor, ME, USADepartments of Medicine and Pediatrics, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL, USADepartments of Medicine and Pediatrics, Section of Endocrinology, Diabetes, and Metabolism, University of Chicago, Chicago, IL, USADepartment of Pathology, University of Florida Diabetes Institute, College of Medicine, Gainesville, FL, USADepartment of Medicine, Diabetes Division, Diabetes Center of Excellence, University of Massachusetts Medical School, Worcester, MA, USAHudsonAlpha Institute for Biotechnology, Huntsville, AL, USAHudsonAlpha Institute for Biotechnology, Huntsville, AL, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USADepartment of Medicine, Division of Diabetes, Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; Corresponding authorSummary: Many patients with type 1 diabetes (T1D) have residual β cells producing small amounts of C-peptide long after disease onset but develop an inadequate glucagon response to hypoglycemia following T1D diagnosis. The features of these residual β cells and α cells in the islet endocrine compartment are largely unknown, due to the difficulty of comprehensive investigation. By studying the T1D pancreas and isolated islets, we show that remnant β cells appeared to maintain several aspects of regulated insulin secretion. However, the function of T1D α cells was markedly reduced, and these cells had alterations in transcription factors constituting α and β cell identity. In the native pancreas and after placing the T1D islets into a non-autoimmune, normoglycemic in vivo environment, there was no evidence of α-to-β cell conversion. These results suggest an explanation for the disordered T1D counterregulatory glucagon response to hypoglycemia. : Brissova et al. find that β cells in the type 1 diabetic (T1D) pancreas maintain several functional and molecular features, but α cells have impaired glucagon secretion and an altered gene expression profile. These findings provide insight into the mechanism of α cell dysfunction in T1D. Keywords: type 1 diabetes, glucagon, insulin, pancreatic islet, alpha cells, humanhttp://www.sciencedirect.com/science/article/pii/S2211124718302134 |
| spellingShingle | Marcela Brissova Rachana Haliyur Diane Saunders Shristi Shrestha Chunhua Dai David M. Blodgett Rita Bottino Martha Campbell-Thompson Radhika Aramandla Gregory Poffenberger Jill Lindner Fong Cheng Pan Matthias G. von Herrath Dale L. Greiner Leonard D. Shultz May Sanyoura Louis H. Philipson Mark Atkinson David M. Harlan Shawn E. Levy Nripesh Prasad Roland Stein Alvin C. Powers α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes Cell Reports |
| title | α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes |
| title_full | α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes |
| title_fullStr | α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes |
| title_full_unstemmed | α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes |
| title_short | α Cell Function and Gene Expression Are Compromised in Type 1 Diabetes |
| title_sort | α cell function and gene expression are compromised in type 1 diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718302134 |
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