LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol
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LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol. / Nøhr, Mark Klitgaard; Dudele, Anete; Poulsen, Morten Møller; Ebbesen, Lene Hyldahl; Radko, Yulia; Christensen, Lars P.; Jessen, Niels; Richelsen, Bjørn; Lund, Sten; Pedersen, Steen Bønløkke.
I: PloS one, Bind 11, Nr. 1, e0146840, 2016.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - LPS-Enhanced Glucose-Stimulated Insulin Secretion Is Normalized by Resveratrol
AU - Nøhr, Mark Klitgaard
AU - Dudele, Anete
AU - Poulsen, Morten Møller
AU - Ebbesen, Lene Hyldahl
AU - Radko, Yulia
AU - Christensen, Lars P.
AU - Jessen, Niels
AU - Richelsen, Bjørn
AU - Lund, Sten
AU - Pedersen, Steen Bønløkke
PY - 2016
Y1 - 2016
N2 - UNLABELLED: Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P < 0.001). This aberration in insulin and glucose homeostasis was normalized by resveratrol.IN CONCLUSION: Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.
AB - UNLABELLED: Low-grade inflammation is seen with obesity and is suggested to be a mediator of insulin resistance. The eliciting factor of low-grade inflammation is unknown but increased permeability of gut bacteria-derived lipopolysaccharides (LPS) resulting in endotoxemia could be a candidate. Here we test the effect of LPS and the anti-inflammatory compound resveratrol on glucose homeostasis, insulin levels and inflammation. Mice were subcutaneously implanted with osmotic mini pumps infusing either low-dose LPS or saline for 28 days. Half of the mice were treated with resveratrol delivered through the diet. LPS caused increased inflammation of the liver and adipose tissue (epididymal and subcutaneous) together with enlarged spleens and increased number of leukocytes in the blood. Resveratrol specifically reduced the inflammatory status in epididymal fat (reduced expression of TNFa and Il1b, whereas the increased macrophage infiltration was unaltered) without affecting the other tissues investigated. By LC-MS, we were able to quantitate resveratrol metabolites in epididymal but not subcutaneous adipose tissue. LPS induced insulin resistance as the glucose-stimulated insulin secretion during an oral glucose tolerance test was increased despite similar plasma glucose level resulting in an increase in the insulinogenic index (IGI; delta0-15insulin/delta0-15glucose) from 13.73 to 22.40 pmol/mmol (P < 0.001). This aberration in insulin and glucose homeostasis was normalized by resveratrol.IN CONCLUSION: Low-dose LPS enhanced the glucose-stimulated insulin secretion without affecting the blood glucose suggesting increased insulin resistance. Resveratrol restored LPS-induced alteration of the insulin secretion and demonstrated anti-inflammatory effects specifically in epididymal adipose tissue possibly due to preferential accumulation of resveratrol metabolites pointing towards a possible important involvement of this tissue for the effects on insulin resistance and insulin secretion.
KW - Adipose Tissue/pathology
KW - Animals
KW - Antioxidants/chemistry
KW - Blood Glucose/analysis
KW - Body Weight
KW - Epididymis
KW - Gene Expression Profiling
KW - Glucose/chemistry
KW - Glucose Tolerance Test
KW - Homeostasis
KW - Inflammation
KW - Insulin/secretion
KW - Insulin Resistance
KW - Leukocytes/cytology
KW - Lipopolysaccharides/chemistry
KW - Liver/pathology
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Obesity/drug therapy
KW - Osmosis
KW - Stilbenes/chemistry
U2 - 10.1371/journal.pone.0146840
DO - 10.1371/journal.pone.0146840
M3 - Journal article
C2 - 26751381
VL - 11
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e0146840
ER -
ID: 195591582