UNIGE document Scientific Article
previous document  unige:90171  next document
add to browser collection
Title

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

Authors
Reimann, Frank
Gribble, Fiona
show hidden authors show all authors [1 - 10]
Published in Endocrinology. 2016, vol. 157, no. 10, p. 3832-3843
Abstract 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.
Identifiers
PMID: 27547850
Full text
Article (Published version) (2.2 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research group Diabète et régulation des gènes (36)
Citation
(ISO format)
DUSAULCY, Rodolphe et al. 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. In: Endocrinology, 2016, vol. 157, n° 10, p. 3832-3843. https://archive-ouverte.unige.ch/unige:90171

52 hits

0 download

Update

Deposited on : 2016-12-08

Export document
Format :
Citation style :