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Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice.

Ortsäter H, Grankvist N, Wolfram S, Kuehn N, Sjöholm A - Nutr Metab (Lond) (2012)

Bottom Line: EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area.These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG.Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, SE-118 83 Stockholm, Sweden. ake.sjoholm@sodersjukhuset.se.

ABSTRACT

Background: Green tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago, but the mechanisms behind its antidiabetic effect remains elusive. In this work, we address this issue by feeding a green tea extract (TEAVIGO™) with a high content of epigallocatechin gallate (EGCG) or the thiazolidinedione PPAR-γ agonist rosiglitazone, as positive control, to db/db mice, an animal model for diabetes.

Methods: Young (7 week-old) db/db mice were randomized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks. Fasting blood glucose, body weight and food intake was measured along the treatment. Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment. Pancreata were sampled at the end of the study for blinded histomorphometric analysis. Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR.

Results: The results show that, in db/db mice, EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion. EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area. These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG.

Conclusions: This study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus

EGCG treatment of isolated islets of Langerhans ex vivo fails to prevent palmitate-induced phosphorylation of JNK and formation of cleaved caspase 3. Pancreatic islets were isolated from lean C57Bl/6J mice and exposed ex vivo for 24 hours in the absence or presence of 0.5 mM palmitate with or without 5, 10 or 20 μM EGCG. Western blot analyses for phosphorylation of JNK1 (A), JNK2 (B) and formation of the apoptosis marker cleaved caspase 3 (C). Bars represent mean ± SEM for 5 different islet preparations in each group. * denotes P < 0.05 for a palmitate effect, and # denotes P < 0.05 for an EGCG effect using one-way ANOVA in conjunction with Dunnett's multiple comparison test. Representative blots for phosphorylated JNK1 (p-JNK1), phosphorylated JNK2 (p-JNK2) and cleaved caspase 3 (CC3) are shown in D.
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Figure 6: EGCG treatment of isolated islets of Langerhans ex vivo fails to prevent palmitate-induced phosphorylation of JNK and formation of cleaved caspase 3. Pancreatic islets were isolated from lean C57Bl/6J mice and exposed ex vivo for 24 hours in the absence or presence of 0.5 mM palmitate with or without 5, 10 or 20 μM EGCG. Western blot analyses for phosphorylation of JNK1 (A), JNK2 (B) and formation of the apoptosis marker cleaved caspase 3 (C). Bars represent mean ± SEM for 5 different islet preparations in each group. * denotes P < 0.05 for a palmitate effect, and # denotes P < 0.05 for an EGCG effect using one-way ANOVA in conjunction with Dunnett's multiple comparison test. Representative blots for phosphorylated JNK1 (p-JNK1), phosphorylated JNK2 (p-JNK2) and cleaved caspase 3 (CC3) are shown in D.

Mentions: The effects of EGCG alone and on palmitate-induced cytotoxicity were investigated by measuring JNK phosphorylation and cleaved caspase 3 in isolated pancreatic islets exposed to palmitate and EGCG ex vivo. After 24 hours, palmitate induced a 2 to 3-fold increase in JNK1 and JNK2 phosphorylation, which was accompanied with a 3-fold induction of the cleaved form of caspase 3 (Figure 6) thus reflecting apoptosis. Neither 5 nor 10 μM of EGCG had any effect on palmitate-induced cytotoxicity, while 20 μM of EGCG caused a slight increase in JNK phosphorylation and cleaved caspase 3, both in the absence or presence of palmitate (Figure 6).


Diet supplementation with green tea extract epigallocatechin gallate prevents progression to glucose intolerance in db/db mice.

Ortsäter H, Grankvist N, Wolfram S, Kuehn N, Sjöholm A - Nutr Metab (Lond) (2012)

EGCG treatment of isolated islets of Langerhans ex vivo fails to prevent palmitate-induced phosphorylation of JNK and formation of cleaved caspase 3. Pancreatic islets were isolated from lean C57Bl/6J mice and exposed ex vivo for 24 hours in the absence or presence of 0.5 mM palmitate with or without 5, 10 or 20 μM EGCG. Western blot analyses for phosphorylation of JNK1 (A), JNK2 (B) and formation of the apoptosis marker cleaved caspase 3 (C). Bars represent mean ± SEM for 5 different islet preparations in each group. * denotes P < 0.05 for a palmitate effect, and # denotes P < 0.05 for an EGCG effect using one-way ANOVA in conjunction with Dunnett's multiple comparison test. Representative blots for phosphorylated JNK1 (p-JNK1), phosphorylated JNK2 (p-JNK2) and cleaved caspase 3 (CC3) are shown in D.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: EGCG treatment of isolated islets of Langerhans ex vivo fails to prevent palmitate-induced phosphorylation of JNK and formation of cleaved caspase 3. Pancreatic islets were isolated from lean C57Bl/6J mice and exposed ex vivo for 24 hours in the absence or presence of 0.5 mM palmitate with or without 5, 10 or 20 μM EGCG. Western blot analyses for phosphorylation of JNK1 (A), JNK2 (B) and formation of the apoptosis marker cleaved caspase 3 (C). Bars represent mean ± SEM for 5 different islet preparations in each group. * denotes P < 0.05 for a palmitate effect, and # denotes P < 0.05 for an EGCG effect using one-way ANOVA in conjunction with Dunnett's multiple comparison test. Representative blots for phosphorylated JNK1 (p-JNK1), phosphorylated JNK2 (p-JNK2) and cleaved caspase 3 (CC3) are shown in D.
Mentions: The effects of EGCG alone and on palmitate-induced cytotoxicity were investigated by measuring JNK phosphorylation and cleaved caspase 3 in isolated pancreatic islets exposed to palmitate and EGCG ex vivo. After 24 hours, palmitate induced a 2 to 3-fold increase in JNK1 and JNK2 phosphorylation, which was accompanied with a 3-fold induction of the cleaved form of caspase 3 (Figure 6) thus reflecting apoptosis. Neither 5 nor 10 μM of EGCG had any effect on palmitate-induced cytotoxicity, while 20 μM of EGCG caused a slight increase in JNK phosphorylation and cleaved caspase 3, both in the absence or presence of palmitate (Figure 6).

Bottom Line: EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area.These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG.Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, SE-118 83 Stockholm, Sweden. ake.sjoholm@sodersjukhuset.se.

ABSTRACT

Background: Green tea was suggested as a therapeutic agent for the treatment of diabetes more than 70 years ago, but the mechanisms behind its antidiabetic effect remains elusive. In this work, we address this issue by feeding a green tea extract (TEAVIGO™) with a high content of epigallocatechin gallate (EGCG) or the thiazolidinedione PPAR-γ agonist rosiglitazone, as positive control, to db/db mice, an animal model for diabetes.

Methods: Young (7 week-old) db/db mice were randomized and assigned to receive diets supplemented with or without EGCG or rosiglitazone for 10 weeks. Fasting blood glucose, body weight and food intake was measured along the treatment. Glucose and insulin levels were determined during an oral glucose tolerance test after 10 weeks of treatment. Pancreata were sampled at the end of the study for blinded histomorphometric analysis. Islets were isolated and their mRNA expression analyzed by quantitative RT-PCR.

Results: The results show that, in db/db mice, EGCG improves glucose tolerance and increases glucose-stimulated insulin secretion. EGCG supplementation reduces the number of pathologically changed islets of Langerhans, increases the number and the size of islets, and heightens pancreatic endocrine area. These effects occurred in parallel with a reduction in islet endoplasmic reticulum stress markers, possibly linked to the antioxidative capacity of EGCG.

Conclusions: This study shows that the green tea extract EGCG markedly preserves islet structure and enhances glucose tolerance in genetically diabetic mice. Dietary supplementation with EGCG could potentially contribute to nutritional strategies for the prevention and treatment of type 2 diabetes.

No MeSH data available.


Related in: MedlinePlus