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Resveratrol-activated SIRT1 in liver and pancreatic β-cells: a Janus head looking to the same direction of metabolic homeostasis.

Vetterli L, Maechler P - Aging (Albany NY) (2011)

Bottom Line: Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension.The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs.In this review, we discuss specificities of SIRT1 effects in the liver versus pancreatic β-cells, ultimately converging towards metabolic homeostasis at the organism level.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.

ABSTRACT
Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a central role in metabolic homeostasis. SIRT1 is one of the targets of resveratrol, a polyphenol that has been shown to increase lifespan and to protect animal models against high-calorie diet induced obesity and insulin resistance. The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs. Among them, the liver and pancreatic β-cells have been shown to be responsive to resveratrol in a SIRT1-dependent manner. Downstream of SIRT1, transcription factors being activated are tissue-specific, in turn inducing expression of metabolic genes in an apparent paradoxical way. In this review, we discuss specificities of SIRT1 effects in the liver versus pancreatic β-cells, ultimately converging towards metabolic homeostasis at the organism level.

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Acute and chronic effects of resveratrol (RSV) on glucose-stimulated insulin secretion in INS-1E β-cellsAcute effects of RSV (A). Following a 2h pre-incubation period without glucose, INS-1E cells were stimulated for 30 min in KRBH with 2.5 or 15 mM glucose (Glc) in the absence (Control) or presence of 1, 5, and 25 μM of RSV. Values are means ± SE of 6 independent experiments. *p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Control group at 15 mM Glc. Chronic effect of sulfonylureas and RSV (B). INS-1E cells were cultured for 24h in the absence (Ctl) or the presence of 1 μM glibenclamide (Glib), 250 μM tolbutamide (Tolb), 5 μM DIDS, and 25 μM RSV. Next, cells were washed and pre-incubated without drugs and without glucose for 2h. Then, cells were incubated for 30 min in the absence of the tested compounds at 2.5 or 15 mM Glc. Values are means ± SE of 3 independent experiments. * p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Ctl group at 15 mM Glc.
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Figure 1: Acute and chronic effects of resveratrol (RSV) on glucose-stimulated insulin secretion in INS-1E β-cellsAcute effects of RSV (A). Following a 2h pre-incubation period without glucose, INS-1E cells were stimulated for 30 min in KRBH with 2.5 or 15 mM glucose (Glc) in the absence (Control) or presence of 1, 5, and 25 μM of RSV. Values are means ± SE of 6 independent experiments. *p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Control group at 15 mM Glc. Chronic effect of sulfonylureas and RSV (B). INS-1E cells were cultured for 24h in the absence (Ctl) or the presence of 1 μM glibenclamide (Glib), 250 μM tolbutamide (Tolb), 5 μM DIDS, and 25 μM RSV. Next, cells were washed and pre-incubated without drugs and without glucose for 2h. Then, cells were incubated for 30 min in the absence of the tested compounds at 2.5 or 15 mM Glc. Values are means ± SE of 3 independent experiments. * p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Ctl group at 15 mM Glc.

Mentions: In pancreatic islets, functions and targets of SIRT1 are still poorly characterized, as very few studies have focused on β-cells to date. Metabolic efficiency is crucial for β-cell function as glucose metabolism is tightly coupled to the control of insulin secretion [11]. Originally, two papers have shown that SIRT1 positively regulates glucose-stimulated insulin secretion in pancreatic β-cells [12, 13]. The SIRT1 activator resveratrol potentiates glucose-stimulated insulin secretion, both acutely and secondary to chronic treatment. Acutely, resveratrol effects are observed already at 1μM in INS-1E insulinoma cells (Figure 1A). Following a 24-hour exposure, the effects of resveratrol are maintained even after removal of the compound, as observed in INS-1E cells and human islets [14]. In islets obtained from a type 2 diabetic donor, resveratrol was reported to partially restore the secretory response to glucose [14]. Several alternative mechanisms may explain the chronic effects of resveratrol on insulin secreting cells.


Resveratrol-activated SIRT1 in liver and pancreatic β-cells: a Janus head looking to the same direction of metabolic homeostasis.

Vetterli L, Maechler P - Aging (Albany NY) (2011)

Acute and chronic effects of resveratrol (RSV) on glucose-stimulated insulin secretion in INS-1E β-cellsAcute effects of RSV (A). Following a 2h pre-incubation period without glucose, INS-1E cells were stimulated for 30 min in KRBH with 2.5 or 15 mM glucose (Glc) in the absence (Control) or presence of 1, 5, and 25 μM of RSV. Values are means ± SE of 6 independent experiments. *p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Control group at 15 mM Glc. Chronic effect of sulfonylureas and RSV (B). INS-1E cells were cultured for 24h in the absence (Ctl) or the presence of 1 μM glibenclamide (Glib), 250 μM tolbutamide (Tolb), 5 μM DIDS, and 25 μM RSV. Next, cells were washed and pre-incubated without drugs and without glucose for 2h. Then, cells were incubated for 30 min in the absence of the tested compounds at 2.5 or 15 mM Glc. Values are means ± SE of 3 independent experiments. * p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Ctl group at 15 mM Glc.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117460&req=5

Figure 1: Acute and chronic effects of resveratrol (RSV) on glucose-stimulated insulin secretion in INS-1E β-cellsAcute effects of RSV (A). Following a 2h pre-incubation period without glucose, INS-1E cells were stimulated for 30 min in KRBH with 2.5 or 15 mM glucose (Glc) in the absence (Control) or presence of 1, 5, and 25 μM of RSV. Values are means ± SE of 6 independent experiments. *p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Control group at 15 mM Glc. Chronic effect of sulfonylureas and RSV (B). INS-1E cells were cultured for 24h in the absence (Ctl) or the presence of 1 μM glibenclamide (Glib), 250 μM tolbutamide (Tolb), 5 μM DIDS, and 25 μM RSV. Next, cells were washed and pre-incubated without drugs and without glucose for 2h. Then, cells were incubated for 30 min in the absence of the tested compounds at 2.5 or 15 mM Glc. Values are means ± SE of 3 independent experiments. * p<0.05, **p<0.01 versus 2.5 mM Glc of the corresponding group; §p<0.05 versus Ctl group at 15 mM Glc.
Mentions: In pancreatic islets, functions and targets of SIRT1 are still poorly characterized, as very few studies have focused on β-cells to date. Metabolic efficiency is crucial for β-cell function as glucose metabolism is tightly coupled to the control of insulin secretion [11]. Originally, two papers have shown that SIRT1 positively regulates glucose-stimulated insulin secretion in pancreatic β-cells [12, 13]. The SIRT1 activator resveratrol potentiates glucose-stimulated insulin secretion, both acutely and secondary to chronic treatment. Acutely, resveratrol effects are observed already at 1μM in INS-1E insulinoma cells (Figure 1A). Following a 24-hour exposure, the effects of resveratrol are maintained even after removal of the compound, as observed in INS-1E cells and human islets [14]. In islets obtained from a type 2 diabetic donor, resveratrol was reported to partially restore the secretory response to glucose [14]. Several alternative mechanisms may explain the chronic effects of resveratrol on insulin secreting cells.

Bottom Line: Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension.The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs.In this review, we discuss specificities of SIRT1 effects in the liver versus pancreatic β-cells, ultimately converging towards metabolic homeostasis at the organism level.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Physiology and Metabolism, University of Geneva Medical Center, Geneva, Switzerland.

ABSTRACT
Sirtuins are energy sensors which mediate effects of calorie restriction-induced lifespan extension. The mammalian sirtuin homolog SIRT1 is a protein deacetylase playing a central role in metabolic homeostasis. SIRT1 is one of the targets of resveratrol, a polyphenol that has been shown to increase lifespan and to protect animal models against high-calorie diet induced obesity and insulin resistance. The beneficial effects of resveratrol mediated by SIRT1 activation can be contributed by different organs. Among them, the liver and pancreatic β-cells have been shown to be responsive to resveratrol in a SIRT1-dependent manner. Downstream of SIRT1, transcription factors being activated are tissue-specific, in turn inducing expression of metabolic genes in an apparent paradoxical way. In this review, we discuss specificities of SIRT1 effects in the liver versus pancreatic β-cells, ultimately converging towards metabolic homeostasis at the organism level.

Show MeSH
Related in: MedlinePlus