The lack of effectiveness of (−)-epicatechin against alloxan induced diabetes in Wistar rats

Sheehan, Erin; Stiff, Dwight D.; Duah, Francis; Slatkin, David J.; Schiff, Paul L.; Zemaitis, Michael A.

doi:10.1016/0024-3205(83)90246-1

Cited by 20 publications

(13 citation statements)

References 5 publications

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“…Furthermore, EGCG was reported to stimulate insulin secretion and to have insulin-like activity [25-27]. In previous work evaluating the effect of EGCG against diabetes induced in rats by the β cell toxin STZ, EGCG restored the diabetic state to normal as in other reports [23,24,28]. More recently, green tea and green tea extracts were demonstrated to beneficially modify glucose metabolism in experimental models of type 2 diabetes [29,30].…”

Section: Discussionmentioning

confidence: 86%

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

Ortsäter

Grankvist

Wolfram³

et al. 2012

Nutr Metab (Lond)

140

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BackgroundGreen 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.MethodsYoung (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.ResultsThe 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.ConclusionsThis 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.

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Section: Discussionmentioning

confidence: 86%

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

Ortsäter

Grankvist

Wolfram³

et al. 2012

Nutr Metab (Lond)

140

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“…28 However, the study performed by Sheehan et al showed no effect on BS by administering (-)-epicatechin in alloxan-induced diabetic rats. 29 Similarly, in a study by Bone et al, the beneficial effects of (-)-epicatechin in STZ-diabetic animals could not be demonstrated. 30 Quercetin, an antioxidant bioflavonoid was capable of augmenting liver glycogen content and significantly reducing serum glucose concentration in a study performed by Nuraliev et al on alloxaninduced diabetic rats.…”

Section: Discussionmentioning

confidence: 93%

Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

et al. 2010

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Objectives:To investigate the effect of silymarin and milk thistle extract on the progression of diabetic nephropathy (DN) in rats. Methods: Diabetes was induced with a single intraperitoneal (IP) injection of streptozotocin (STZ) (60 mg/kg). Silymarin (100 mg/kg/d) or the extract (1.2 g/kg/d) was gavaged for 4 weeks. Blood glucose (BS), serum urea (S u ), serum creatinine (S cr ), and 24-h urine protein (Up) were measured and glomerular filtration rate (GFR) was calculated. Concentration of thiobarbituric acid reactive species (TBARS) and activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were evaluated in the renal tissue. Results: Data were expressed as mean ± SEM. Silymarin or the extract had no significant effect on BS, S cr , and GFR. Both milk thistle extract and silymarin, respectively, decreased S u (mg/dL) (87.1 ± 7.78, p < 0.001; 84.5 ± 7.15, p < 0.001), Up (mg) (5.22 ± 1.56, p = 0.014; 5.67 ± 0.86, p = 0.034), and tissue TBARS (nmol/mg protein) (0.67 ± 0.04, p < 0.001; 0.63 ± 0.07, p < 0.001) in diabetic rats, compared to diabetic control (DC) (S u : 131.0 ± 4.55, Up: 8.3 ± 0.84, TBARS: 0.94 ± 0.06). Both the extract and silymarin could increase the activity of CAT (IU/mg protein) (25.5 ± 4.0, p = 0.005; 20 ± 1.8, p = 0.16) and GPx (IU/mg protein) (0.86 ± 0.05, p = 0.005; 0.74 ± 0.04, p = 0.10), respectively, in diabetic rats compared to DC (CAT = 14.4 ± 2.0, GPx = 0.57 ± 0.02). Conclusion: Milk thistle extract, to a lesser extent silymarin, can attenuate DN in rats possibly by increasing kidney CAT and GPx activity and decreasing lipid peroxidation in renal tissue.

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“…interaction with calmodulin (Nishino, Naitoh, Iwashima & Umezawa, 1984) and protein kinase C (Gschwendt, Horn, Kittstein & Marks, 1983). Re¬ cently, the role of epicatechin as an antidiabetic agent has been questioned since subsequent attempts to confirm the original observations of Chakravarthy et al (1981,1982) have not been uniformly successful (Sheehan et al 1983;Bone, Hii, Brown et al 1985).…”

Section: Discussionmentioning

confidence: 92%

“…Since prevention of photo-oxidation of epicatechin by ascorbic acid does not affect hormone release (Hii & Howell, 1984a), suggesting that either light-induced destruction during the experiment was minimal or that flavonoids retained their activities despite the struc¬ tural changes, ascorbic acid was omitted from the secretion experiments in the present study. Further¬ more, Sheehan, Stiff, Duah et al (1983) reported that epicatechin remained stable in solution for more than 4 days.…”

Section: Measurement Of Insulin Secretionmentioning

confidence: 96%

Effects of flavonoids on insulin secretion and 45Ca2+ handling in rat islets of Langerhans

Hii¹,

Howell²

1985

Journal of Endocrinology

151

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The effects of some flavonoids, a group of naturally occurring pigments one of which has been claimed to possess antidiabetic activities, on insulin release and 45Ca2+ handling have been studied in isolated rat islets of Langerhans. Insulin release was enhanced by approximately 44-70% when islets were exposed to either (-)epicatechin (0.8 mmol/l) or quercetin (0.01-0.1 mmol/l); others such as naringenin (0.1 mmol/l) and chrysin (0.08 mmol/l) inhibited hormone release by approximately 40-60%. These effects were observed only in the presence of 20 mmol glucose/l. Quercetin (0.01 mmol/l) and (-)epicatechin (0.8 mmol/l) both inhibited 45Ca2+ efflux in the presence and absence of extracellular Ca2+. In the presence of 20 mmol glucose/l both the short-term (5 min) and steady-state (30 min) uptake of 45Ca2+ were significantly increased by either quercetin or (-)epicatechin. These results suggest that the stimulatory compounds such as quercetin and (-)epicatechin may, at least in part, exert their effects on insulin release via changes in Ca2+ metabolism.

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The lack of effectiveness of (−)-epicatechin against alloxan induced diabetes in Wistar rats

Cited by 20 publications

References 5 publications

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

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

Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats

Effects of flavonoids on insulin secretion and 45Ca2+ handling in rat islets of Langerhans

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