Endocrinol Metab.  2015 Jun;30(2):216-220. 10.3803/EnM.2015.30.2.216.

Glucagon-Like Peptide-1 Increases Mitochondrial Biogenesis and Function in INS-1 Rat Insulinoma Cells

• Kang MY
• Oh TJ
• Cho YM

• KMID: 2282013
• DOI: http://doi.org/10.3803/EnM.2015.30.2.216

Abstract

Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic beta-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic beta-cells. We treated INS-1 rat insulinoma cells with GLP-1 or exendin-4 for 48 hours and measured mitochondrial mass and function. Both GLP-1 and exendin-4 increased mitochondrial mass by approximately 20%. The mitochondria/cytosol ratio was increased from 7.60+/-3.12% to 10.53+/-2.70% by exendin-4. In addition, GLP-1 increased the mitochondrial membrane potential and oxygen consumption. Proliferator-activated receptor-gamma coactivator 1alpha expression was increased approximately 2-fold by GLP-1 treatment. In conclusion, the present study presents evidence for a new mechanism of action by which GLP-1 improves pancreatic beta-cell function via enhanced mitochondrial mass and performance.

Keyword

Glucagon-like peptide-1; Mitochondria; Diabetes mellitus; Beta cell; Insulin

MeSH Terms

Animals
Diabetes Mellitus
Glucagon-Like Peptide 1*
Incretins
Insulin
Insulinoma*
Membrane Potential, Mitochondrial
Mitochondria
Organelle Biogenesis*
Oxygen Consumption
Rats*
Glucagon-Like Peptide 1
Incretins
Insulin

Figure

• 

  Fig. 1 Effects of glucagon-like peptide-1 (GLP-1) or exendin-4 on insulin secretion (A, n=6), mitochondrial mass (C, n=10), mitochondrial density (E, n=10), and proliferator-activated receptor-gamma coactivator 1 α (PGC1α) expression (F) in INS-1 cells. (B) A representative fluorescence activated cell sorting analysis for 10-n-nonyl-acridine orange staining (NAO) intensity, as summarized in (C). (D) Representative transmission electron microscopy images used to estimate the mitochondria/cytosol area ratios shown in concentration (conc). MFI, mean fluorescence intensity; GAPDH, glyceraldehyde 3-phosphate dehydrogenase. aP<0.05; bP<0.01 compared with the control.

• 

  Fig. 2 Glucagon-like peptide-1 (GLP-1) increases mitochondria membrane potential (A, n=6) and cellular oxygen consumption rate (B, n=4). TMRE, tetramethylrhodamine ethyl ester perchlorate; MFI, mean fluorescence intensity. aP<0.05; bP<0.01 compared with control.

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