Epigallocatechin gallate prevents autoimmune diabetes induced by multiple low doses of streptozotocin in mice

Abstract

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired beta-cell function in high glucose condition. By the screening of various natural products blocking beta-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced beta-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kappaB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of beta-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.

Epigallocatechin-3-gallate (EGCG), A Green Tea Polyphenol, Suppresses Hepatic Gluconeogenesis through 5′-AMP-activated Protein Kinase

“…EGCG has been shown to be involved in regulation of a variety of metabolic processes and has been used as an anti-obesity reagent in animal models and in humans (3)(4)(5)(6). Although its effectiveness in the treatment of human diabetes has not been established, EGCG has been shown in rodents to be effective in preventing the development of Type I diabetes and treatment of Type II diabetes (7,8). The mechanism of EGCG regulation of metabolism remains to be established although a variety of different roles for EGCG have been suggested.…”

Inhibitory effect of green tea (−)-epigallocatechin gallate on resistin gene expression in 3T3-L1 adipocytes depends on the ERK pathway

“…In particular, green tea (Ϫ)-epigallocatechin gallate (EGCG; Fig. 1), the majority of GTC, lowers the incidence of streptozotocin-induced diabetes (42) and reduces body weight, body fat, and blood levels of glucose and lipid in leptin receptor-defective obese rats (20,21). In addition, EGCG protects pancreatic cells (42), enhances insulin activity (2), represses hepatic glucose production (51), reduces food uptake and absorption (20,27), stimulates thermogenesis (13) and lipid excretion (27), and modulates insulin-leptin endocrine systems (20).…”

Compounds with Antioxidant Capacity as Potential Tools Against Several Oxidative Stress Related Disorders: Fact or Artifact?

“…Thus, EGCG protects pancreatic cells (Song et al, 2003), enhances insulin activity (Dhawan et al, 2002), represses hepatic glucose production (Waltner-Law et al, 2002), reduces food uptake and absorption (Kao et al, 2000), stimulates thermogenesis by increasing the uncoupling protein 2 (UCP2) and lipid excretion (Dulloo et al, 1999;Liao, 2001), and modulates insulin-leptin endocrine systems (Kao et al, 2000). Moreover, EGCG inhibits the sodium-dependent glucose transporter (Kobayashi et al, 2000) and represses various enzymes related to lipid metabolism, such as acetyl-CoA carboxylase, fatty acid synthase, pancreatic lipase, gastric lipase, and lipooxygenase (Liao, 2001;Wang & Tian, 2001) as well as lipolytic genes such as hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in adipose tissue (Lee et al, 2009).…”

“…Moreover, several "in vivo" studies demonstrated that green tea extracts or EGCG dietary supplementation decreased both body and adipose tissue weights (Park et al, 2011;Choo, 2003;Hasegawa et al, 2003), improved insulin sensitivity and glucose tolerance (Cao et al, 2007;Serisier et al, 2008) and had beneficial effects on prevention of hypertension (Ihm et al, 2009) and modulation of plasma cholesterol (Bursill et al, 2007), conditions linked to metabolic syndrome. In addition, it lowers the incidence of streptozotocin-induced diabetes (Song et al, 2003) and reduces body weight, body fat, and blood levels of glucose and lipid in leptin receptor-defective obese rats (Kao et al, 2000).…”