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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

Effects of 10 weeks of treatment with EGCG or rosiglitazone on pancreatic islet morphology and β cell area. Light microscopic appearance and histomorphometric analysis of pancreatic islet morphology and β-cell area in control db/db mice and db/db mice receiving dietary supplementation with 1% (w/w) EGCG or 0.0021% (w/w) rosiglitazone (Rosi) for 10 weeks. H&E staining was used and original magnification was 200 x. Bars represent mean ± SEM for 9 mice in each group. * denotes P < 0.001 (number of pathological islets) and P < 0.01 (β cell area) for chance differences vs controls using one-way ANOVA in conjunction with Dunnett's multiple comparison test.
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Figure 3: Effects of 10 weeks of treatment with EGCG or rosiglitazone on pancreatic islet morphology and β cell area. Light microscopic appearance and histomorphometric analysis of pancreatic islet morphology and β-cell area in control db/db mice and db/db mice receiving dietary supplementation with 1% (w/w) EGCG or 0.0021% (w/w) rosiglitazone (Rosi) for 10 weeks. H&E staining was used and original magnification was 200 x. Bars represent mean ± SEM for 9 mice in each group. * denotes P < 0.001 (number of pathological islets) and P < 0.01 (β cell area) for chance differences vs controls using one-way ANOVA in conjunction with Dunnett's multiple comparison test.

Mentions: During progression to diabetes islet structure degenerate [13]. To evaluate if EGCG and/or rosiglitazone were able to prevent islet degeneration in the db/db mouse model we used light microscopy to examine islet structure after insulin immunostaining. As shown in Figure 3, 10 weeks of EGCG treatment caused a significant although not to same extent as rosiglitazone, decrease in the number of islets showing pathological changes. Treatment with EGCG for 10 weeks did not significantly influence the size of the β cell area relative to the total endocrine area in islets, whereas rosiglitazone modestly increased β cell area. After 10 weeks of EGCG treatment there was a significant increase in the number of islets per area of pancreas, of comparable magnitude to that evoked by rosiglitazone (Figure 4). Lastly, as shown in Figure 5, 10 weeks of EGCG treatment caused a significant increase in the size of the pancreatic islets, again of comparable magnitude to that evoked by rosiglitazone. Together with the hyperplastic effects of the substances noted in Figure 4, this gave rise to > 2-fold increase in pancreatic endocrine area. The presence of isolated, invasive acinar cells among the endocrine cells in the islets from untreated mice (Figure 5, left panel) suggests that these are degenerated islets. Note the sparsely granulated endocrine and heavily granulated acinar cells located within the degenerate islets. In contrast, note the pronounced granulation of the β cells and the apparently normal morphology of islets from mice treated with EGCG (middle) and rosiglitazone (right).


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)

Effects of 10 weeks of treatment with EGCG or rosiglitazone on pancreatic islet morphology and β cell area. Light microscopic appearance and histomorphometric analysis of pancreatic islet morphology and β-cell area in control db/db mice and db/db mice receiving dietary supplementation with 1% (w/w) EGCG or 0.0021% (w/w) rosiglitazone (Rosi) for 10 weeks. H&E staining was used and original magnification was 200 x. Bars represent mean ± SEM for 9 mice in each group. * denotes P < 0.001 (number of pathological islets) and P < 0.01 (β cell area) for chance differences vs controls using one-way ANOVA in conjunction with Dunnett's multiple comparison test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3298777&req=5

Figure 3: Effects of 10 weeks of treatment with EGCG or rosiglitazone on pancreatic islet morphology and β cell area. Light microscopic appearance and histomorphometric analysis of pancreatic islet morphology and β-cell area in control db/db mice and db/db mice receiving dietary supplementation with 1% (w/w) EGCG or 0.0021% (w/w) rosiglitazone (Rosi) for 10 weeks. H&E staining was used and original magnification was 200 x. Bars represent mean ± SEM for 9 mice in each group. * denotes P < 0.001 (number of pathological islets) and P < 0.01 (β cell area) for chance differences vs controls using one-way ANOVA in conjunction with Dunnett's multiple comparison test.
Mentions: During progression to diabetes islet structure degenerate [13]. To evaluate if EGCG and/or rosiglitazone were able to prevent islet degeneration in the db/db mouse model we used light microscopy to examine islet structure after insulin immunostaining. As shown in Figure 3, 10 weeks of EGCG treatment caused a significant although not to same extent as rosiglitazone, decrease in the number of islets showing pathological changes. Treatment with EGCG for 10 weeks did not significantly influence the size of the β cell area relative to the total endocrine area in islets, whereas rosiglitazone modestly increased β cell area. After 10 weeks of EGCG treatment there was a significant increase in the number of islets per area of pancreas, of comparable magnitude to that evoked by rosiglitazone (Figure 4). Lastly, as shown in Figure 5, 10 weeks of EGCG treatment caused a significant increase in the size of the pancreatic islets, again of comparable magnitude to that evoked by rosiglitazone. Together with the hyperplastic effects of the substances noted in Figure 4, this gave rise to > 2-fold increase in pancreatic endocrine area. The presence of isolated, invasive acinar cells among the endocrine cells in the islets from untreated mice (Figure 5, left panel) suggests that these are degenerated islets. Note the sparsely granulated endocrine and heavily granulated acinar cells located within the degenerate islets. In contrast, note the pronounced granulation of the β cells and the apparently normal morphology of islets from mice treated with EGCG (middle) and rosiglitazone (right).

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