Resveratrol and curcumin enhance pancreatic β-cell function by inhibiting phosphodiesterase activity

  1. Josephine M Egan1
  1. 1Laboratory of Clinical Investigation
    2Laboratory of Cardiovascular Science, National Institute on Aging, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd, Baltimore, Maryland 21224, USA
  1. Correspondence should be addressed to J M Egan; Email: eganj{at}grc.nia.nih.gov
  1. Figure 1

    Resveratrol (RES) and curcumin (CUR) enhance insulin secretion in pancreatic β-cells. Mouse β-Min6 cells were treated with (A) RES or (B) CUR for 2 h under low- (1 mmol/l) or high- (25 mmol/l) glucose conditions. Primary human islets (n=2 donors) were incubated with (C) RES or (D) CUR for 2 h under low- (5 mmol/l) or high- (25 mmol/l) glucose conditions. Supernatants from triplicate samples were analyzed for insulin secretion (*P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001). Data are representative of at least three independent experiments.

  2. Figure 2

    Resveratrol (RES) and curcumin (CUR) increase intracellular cAMP levels in β-cells. Mouse β-Min6 cells were treated with (A) RES or (B) CUR for 2 h under low- (1 mmol/l) or high- (25 mmol/l) glucose conditions. Primary human islets were treated with (C) RES or (D) CUR for 2 h under low- (5 mmol/l) or high- (25 mmol/l) glucose conditions (n=2 donors). Cells were lysed and assessed for intracellular cAMP levels after normalizing to protein content in triplicates (*P<0.05). Data are representative of at least three independent experiments.

  3. Figure 3

    PDE blockade leads to enhanced insulin secretion and intracellular cAMP production. Mouse β-Min6 cells were treated with PDE inhibitor IBMX (50 μmol/l) for 2 h under low- (1 mmol/l) or high- (25 mmol/l) glucose conditions. Cells were examined for (A) insulin secretion and (B) intracellular cAMP levels (normalized to protein content; *P<0.05, **P<0.01, and ****P<0.0001). Samples were run in triplicate, and data are representative of at least three independent experiments.

  4. Figure 4

    Resveratrol (RES) and curcumin (CUR) reduce PDE expression in β-cells. (A) Mouse β-Min6 cells and (B) human HP62 β-cells were incubated with vehicle, RES (0.1 μmol/l), or CUR (1 pmol/l) for 2 h under low- (1 mmol/l) or high- (25 mmol/l) glucose conditions. (C) Primary human islets (n=3 donors) were incubated with vehicle, RES (10 μmol/l), or CUR (100 pmol/l) for 2 h under low (5 mmol/l) or high (25 mmol/l) glucose conditions. Samples, ran in triplicate, were analyzed for relative PDE mRNA expression using quantitative RT-PCR and results are expressed as mean±s.e.m. (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001). Data are representative of at least three independent experiments.

  5. Figure 5

    Resveratrol (RES) and curcumin (CUR) impede PDE activity in pancreatic β-cells. (A) Mouse β-Min6 cells and (B) human HP62 β-cells were cultured for 2 h under low- (1 mmol/l) or high- (25 mmol/l) glucose conditions. (C) Primary human islets (n=2 donors) were cultured for 2 h under low- (5 mmol/l) or high- (25 mmol/l) glucose conditions. Cell lysates were treated with vehicle, RES, or CUR and analyzed for relative PDE activity using a bioluminescence reaction assay. Samples were run in triplicates and the mean was plotted (*P<0.05, **P<0.01, ***P<0.001, and ****P<0.0001). Data are representative of at least three independent experiments.

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