التفاصيل البيبلوغرافية
| العنوان: |
Functional and Molecular Adaptations of Enteroendocrine L-Cells in Male Obese Mice Are Associated With Preservation of Pancreatic α-Cell Function and Prevention of Hyperglycemia |
| المؤلفون: |
Dusaulcy, Rodolphe, Handgraaf, Sandra Gabrielle, Skarupelova, Svetlana, Visentin, Florian, Vesin, Christian, Heddad Masson, Mounia, Reimann, Frank, Gribble, Fiona, Philippe, Jacques, Gosmain, Yvan |
| المصدر: |
ISSN: 0013-7227 ; Endocrinology, vol. 157, no. 10 (2016) p. 3832-3843. |
| سنة النشر: |
2016 |
| المجموعة: |
Université de Genève: Archive ouverte UNIGE |
| مصطلحات موضوعية: |
info:eu-repo/classification/ddc/612, info:eu-repo/classification/ddc/616 |
| الوصف: |
Glucose homeostasis depends on the coordinated secretion of glucagon, insulin, and Glucagon-like peptide (GLP)-1 by pancreas and intestine. Obesity, which is associated with an increased risk of developing insulin resistance and type 2 diabetes, affects the function of these organs. Here, we investigate the functional and molecular adaptations of proglucagon-producing cells in obese mice to better define their involvement in type 2 diabetes development. We used GLU-Venus transgenic male mice specifically expressing Venus fluorochrome in proglucagon-producing cells. Mice were subjected to 16 weeks of low-fat diet or high-fat diet (HFD) and then subdivided by measuring glycated hemoglobin (HbA1c) in 3 groups: low-fat diet mice and I-HFD (glucose-intolerant) mice with similar HbA1c and H-HFD (hyperglycemic) mice, which exhibited higher HbA1c. At 16 weeks, both HFD groups exhibited similar weight gain, hyperinsulinemia, and insulin resistance. However, I-HFD mice exhibited better glucose tolerance compared with H-HFD mice. I-HFD mice displayed functional and molecular adaptations of enteroendocrine L-cells resulting in increased intestinal GLP-1 biosynthesis and release as well as maintained pancreatic α- and β-cell functions. By contrast, H-HFD mice exhibited dysfunctional L, α- and β-cells with increased β- and L-cell numbers. Administration of the GLP-1R antagonist Exendin9-39 in I-HFD mice led to hyperglycemia and alterations of glucagon secretion without changes in insulin secretion. Our results highlight the cross-talk between islet and intestine endocrine cells and indicate that a compensatory adaptation of L-cell function in obesity plays an important role in preserving glucose homeostasis through the control of pancreatic α-cell functions. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/27547850; https://archive-ouverte.unige.ch/unige:90171; unige:90171 |
| الاتاحة: |
https://archive-ouverte.unige.ch/unige:90171 |
| Rights: |
info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: |
edsbas.9C79E440 |
| قاعدة البيانات: |
BASE |