Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock

Anne Lykkegaard Widlund, H. Wang, Y. Guan, L.B. Becker, J.A. Bauer, P.M. Reilly, P.M. Reilly, C.A Sims

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Background: Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. Methods: With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model AssessmentYInsulin Resistance index was used to quantify insulin resistance. Results: RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 T 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 T 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 T 56.6 ng/mL vs. 187.3 T 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model AssessmentYInsulin Resistance index (1.30 ± 0.42 vs. 4.18 T 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Conclusion: Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion
    OriginalsprogEngelsk
    TidsskriftJournal of Trauma
    Vol/bind77
    Udgave nummer6
    Sider (fra-til)926-933
    ISSN0022-5282
    DOI
    StatusUdgivet - 2014

    Citer dette

    Widlund, A. L., Wang, H., Guan, Y., Becker, L. B., Bauer, J. A., Reilly, P. M., ... Sims, C. A. (2014). Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock. Journal of Trauma, 77(6), 926-933. https://doi.org/10.1097/TA.0000000000000358
    Widlund, Anne Lykkegaard ; Wang, H. ; Guan, Y. ; Becker, L.B. ; Bauer, J.A. ; Reilly, P.M. ; Reilly, P.M. ; Sims, C.A. / Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock. I: Journal of Trauma. 2014 ; Bind 77, Nr. 6. s. 926-933.
    @article{d5bb93b4fe614ad1abbd221a2be65cb8,
    title = "Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock",
    abstract = "Background: Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. Methods: With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model AssessmentYInsulin Resistance index was used to quantify insulin resistance. Results: RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 T 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 T 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 T 56.6 ng/mL vs. 187.3 T 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model AssessmentYInsulin Resistance index (1.30 ± 0.42 vs. 4.18 T 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Conclusion: Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion",
    author = "Widlund, {Anne Lykkegaard} and H. Wang and Y. Guan and L.B. Becker and J.A. Bauer and P.M. Reilly and P.M. Reilly and C.A Sims",
    year = "2014",
    doi = "10.1097/TA.0000000000000358",
    language = "English",
    volume = "77",
    pages = "926--933",
    journal = "Journal of Trauma",
    issn = "0022-5282",
    publisher = "Lippincott Williams & Wilkins",
    number = "6",

    }

    Widlund, AL, Wang, H, Guan, Y, Becker, LB, Bauer, JA, Reilly, PM, Reilly, PM & Sims, CA 2014, 'Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock', Journal of Trauma, bind 77, nr. 6, s. 926-933. https://doi.org/10.1097/TA.0000000000000358

    Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock. / Widlund, Anne Lykkegaard; Wang, H.; Guan, Y.; Becker, L.B.; Bauer, J.A.; Reilly, P.M.; Reilly, P.M.; Sims, C.A.

    I: Journal of Trauma, Bind 77, Nr. 6, 2014, s. 926-933.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock

    AU - Widlund, Anne Lykkegaard

    AU - Wang, H.

    AU - Guan, Y.

    AU - Becker, L.B.

    AU - Bauer, J.A.

    AU - Reilly, P.M.

    AU - Reilly, P.M.

    AU - Sims, C.A

    PY - 2014

    Y1 - 2014

    N2 - Background: Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. Methods: With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model AssessmentYInsulin Resistance index was used to quantify insulin resistance. Results: RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 T 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 T 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 T 56.6 ng/mL vs. 187.3 T 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model AssessmentYInsulin Resistance index (1.30 ± 0.42 vs. 4.18 T 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Conclusion: Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion

    AB - Background: Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. Methods: With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model AssessmentYInsulin Resistance index was used to quantify insulin resistance. Results: RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 T 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 T 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 T 56.6 ng/mL vs. 187.3 T 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model AssessmentYInsulin Resistance index (1.30 ± 0.42 vs. 4.18 T 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Conclusion: Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion

    U2 - 10.1097/TA.0000000000000358

    DO - 10.1097/TA.0000000000000358

    M3 - Journal article

    VL - 77

    SP - 926

    EP - 933

    JO - Journal of Trauma

    JF - Journal of Trauma

    SN - 0022-5282

    IS - 6

    ER -