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

Kang MY, Oh TJ, Cho YM - Endocrinol Metab (Seoul) (2015)

Bottom Line: The mitochondria/cytosol ratio was increased from 7.60±3.12% to 10.53±2.70% by exendin-4.Proliferator-activated receptor-gamma coactivator 1α 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 β-cell function via enhanced mitochondrial mass and performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic β-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic β-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 1α 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 β-cell function via enhanced mitochondrial mass and performance.

No MeSH data available.


Related in: MedlinePlus

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.
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Figure 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.

Mentions: GLP-1 treatment of INS-1 cells for 48 hours enhanced glucose-stimulated insulin secretion (Fig. 1A) and mitochondrial mass (Fig. 1B, C). GLP-1 at 100, 200, and 400 nM increased NAO staining intensity to 121.64±11.54, 127.48±15.47, and 126.94±12.89 MFI, respectively (n=10) (Fig. 1C). A similar result was obtained using another mitochondrial dye (MitoTracker Green, data not shown). When mitochondrial density was measured using a point-counting method on transmission electron microscopy images, the mitochondria/cytosol area ratio was significantly increased by 100 nM exendin-4, from 7.60±3.12% to 10.53±2.70% (Fig. 1D, E). The expression of proliferator-activated receptor-gamma coactivator 1 α (PGC1α), a key regulator of mitochondrial biogenesis, was increased dramatically after 1 hour of GLP-1 treatment; after 4 hours, expression decreased gradually but remained above control levels for up to 48 hours of treatment (Fig. 1F).


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

Kang MY, Oh TJ, Cho YM - Endocrinol Metab (Seoul) (2015)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4508267&req=5

Figure 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.
Mentions: GLP-1 treatment of INS-1 cells for 48 hours enhanced glucose-stimulated insulin secretion (Fig. 1A) and mitochondrial mass (Fig. 1B, C). GLP-1 at 100, 200, and 400 nM increased NAO staining intensity to 121.64±11.54, 127.48±15.47, and 126.94±12.89 MFI, respectively (n=10) (Fig. 1C). A similar result was obtained using another mitochondrial dye (MitoTracker Green, data not shown). When mitochondrial density was measured using a point-counting method on transmission electron microscopy images, the mitochondria/cytosol area ratio was significantly increased by 100 nM exendin-4, from 7.60±3.12% to 10.53±2.70% (Fig. 1D, E). The expression of proliferator-activated receptor-gamma coactivator 1 α (PGC1α), a key regulator of mitochondrial biogenesis, was increased dramatically after 1 hour of GLP-1 treatment; after 4 hours, expression decreased gradually but remained above control levels for up to 48 hours of treatment (Fig. 1F).

Bottom Line: The mitochondria/cytosol ratio was increased from 7.60±3.12% to 10.53±2.70% by exendin-4.Proliferator-activated receptor-gamma coactivator 1α 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 β-cell function via enhanced mitochondrial mass and performance.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT
Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that increases glucose-stimulated insulin secretion in pancreatic β-cells. Since mitochondrial function is crucial to insulin secretion, we hypothesized that GLP-1 may increase mitochondrial biogenesis in pancreatic β-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 1α 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 β-cell function via enhanced mitochondrial mass and performance.

No MeSH data available.


Related in: MedlinePlus