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Scientific article
English

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

Contributors

Dusaulcy, Rodolphe; Handgraaf, Sandra Gabrielle; Skarupelova, Svetlana; Visentin, Florian; Vesin, Christian; Heddad Masson, Mounia; Reimann, Frank; Gribble, Fiona; Philippe, Jacques; Gosmain, Yvan

Published in

Endocrinology, vol. 157, no. 10, p. 3832-3843

Publication date

2016

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.

UNIGE affiliation entities

UNIGE research groups

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. doi: 10.1210/en.2016-1433

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Article (Published version)

Identifiers

Journal ISSN

0013-7227
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Technical informations

Creation

29/11/2016 09:59:00

First validation

29/11/2016 09:59:00

Update

15/03/2023 01:08:19

Status update

15/03/2023 01:08:18

Last indexation

31/10/2024 05:32:01
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