Advances in Clinical and Experimental Medicine
2018, vol. 27, nr 1, January, p. 135–142
Publication type: review article
The significance of anthocyanins in the prevention and treatment of type 2 diabetes
1 Department of Dietetics, Wroclaw Medical University, Poland
Anthocyanins are food compounds which belong to polyphenols and can mainly be found in dark fruits (e.g., blueberries, black currants, cranberries) and vegetables (e.g., red cabbage, radish, eggplant). The results of large research have shown that these compounds play an important role in the prevention of type 2 diabetes (T2D). In rodent studies and in studies with isolated omental adipocytes, it was observed that anthocyanins regulated the carbohydrate metabolism in the body due to the upregulation of GLUT4 (insulinregulated glucose transporter) translocation, increased activation of PPARγ (peroxisome proliferator-activated receptor-γ) in adipose tissue and skeletal muscles as well as increased secretion of adiponectin and leptin. Moreover, these compounds reduced the inflammation status in the body. Studies conducted on humans and experimental animals showed that anthocyanins decrease insulin resistance. This effect may be achieved by the upregulation of GLUT4 gene expression, activation of AMP-activated protein kinase and downregulation of retinol binding protein 4 (RBP4) expression. Anthocyanins also increased the uptake and utilization of glucose by tissues in streptozotocin-induced diabetic rats and mice, and they also protected pancreatic cells against necrosis induced by streptozotocin. Another mechanism that might explain the lower glucose level in the blood after a meal with anthocyanins compared to a meal without them is the inhibition of intestinal α-glucosidase and pancreatic α-amylase by these compounds. Moreover, anthocyanins improve insulin secretion, which can have a special meaning for people with T2D. The evidence from the presented studies suggests that foods rich in anthocyanins may be one of the diet elements supporting the prevention and treatment of T2D.
insulin resistance, type 2 diabetes, anthocyanins, postprandial glycemia, cyanidin-3-O-glucoside
- El Gharras H. Polyphenols: Food sources, properties and applications: A review. Int J Food Sci Technol. 2009;44:2512–2518.
- Ross JA, Kasum CM. Dietary flavonoids: Bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19–34.
- Yao LH, Jiang YM, Shi J, et al. Flavonoids in food and their health benefits. Plant Food Hum Nutr. 2004;59:113–122.
- Bhagwat S, Haytowitz, DB, Holden JM, eds. 2014. USDA Database for the Flavonoid Content of Selected Foods, Release 3.1. U.S. Department of Agriculture, Agricultural Research Service. Nutrient Data Laboratory Home Page: http://www.ars.usda.gov/nutrientdata/flav. Accessed December 29, 2015.
- Jennings A, Welch AA, Fairweather-Tait SJ, et al. Higher anthocyanin intake is associated with lower arterial stiffness and central blood pressure in women. Am J Clin Nutr. 2012;96:781–788.
- Cassidy A, Mukamal KJ, Liu L, Franz M, Eliassen AH, Rimm EB. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation. 2013;127:188–196.
- Hollman PCH, Geelen A, Kromhout D. Dietary flavonol intake may lower stroke risk in men and women. J Nutr. 2010;140:600–604.
- Wedick NM, Pan A, Cassidy A, et al. Dietary flavonoid intakes and risk of type 2 diabetes in US men and women. Am J Clin Nutr. 2012;95:925–933.
- Trujillo ME, Scherer PE. Adipose tissue-derived factors: Impact on health and disease. Endocrine Reviews. 2006;27:762–778.
- Scazzocchio B, Varì R, Filesi C, et al. Cyanidin-3-O-b-glucoside and protocatechuic acid exert insulin-like effects by upregulating PPARγ activity in human omental adipocytes. Diabetes. 2011;60:2234–2244.
- Seymour EM, Tanone II, Urcuyo-Llanes DE, et al. Blueberry intake alters skeletal muscle and adipose tissue peroxisome proliferator-activated receptor activity and reduces insulin resistance in obese rats. J Med Food. 2011;14:1511–1518.
- Tsuda T, Ueno Y, Aoki H, et al. Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. Biochem Biophys Res Commun. 2004;316:149–157.
- Abdelgadir M, Karlsson AF, Berglund L, Berne C. Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus. Diabetol Metab Syndr. 2013;5:15. doi: 10.1186/1758-5996-5-15
- Aleidi S, Issa A, Bustanji H, Khalil M, Bustanji Y. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients. Saudi Pharm J. 2015;23:250–256.
- Tao C, Sifuentes A, Holland WL. Regulation of glucose and lipid homeostasis by adiponectin: Effects on hepatocytes, pancreatic β cells and adipocytes. Best Pract Res Clin Endocrinol Metab. 2014;28:43–58.
- Coppari R, Bjørbæk C. The potential of leptin for treating diabetes and its mechanism of action. Nat Rev Drug Discov. 2012;11:692–708.
- Liu Y, Li D, Zhang Y, Sun R, Xia M. Anthocyanin increases adiponectin secretion and protects against diabetes-related endothelial dysfunction. Am J Physiol Endocrinol Metab. 2014;306:E975-E988.
- De Furia J, Bennett G, Strissel KJ, et al. Dietary blueberry attenuates whole-body insulin resistance in high fat-fed mice by reducing adipocyte death and its inflammatory sequelae. J Nutr. 2009;139:1510–1516.
- Edirisinghe I, Banaszewski K, Cappozzo J, et al. Strawberry anthocyanin and its association with postprandial inflammation and insulin. Br J Nutr. 2011;106:913–922.
- Li D, Zhang Y, Liu Y, Sun R, Xia M. Purified anthocyanin supplementation reduces dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients. J Nutr. 2015;145:742–748.
- Sabokdast M, Habibi-Rezaei M, Moosavi-Movahedi AA, et al. Protection by beta-hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis. DARU. 2015;23:42. doi: 10.1186/s40199-015-0126-5
- Stull AJ, Cash KC, Johnson WD, Champagne CM, Cefalu WT. Bioactives in blueberries improve insulin sensitivity in obese, insulin-resistant men and women. J Nutr. 2010;140:1764–1768.
- Jennings A, Welch AA, Spector T, Macgregor A, Cassidy A. Intakes of anthocyanins and flavones are associated with biomarkers of insulin resistance and inflammation in women. J Nutr. 2014;144:202–208.
- Inaguma T, Han J, Isoda H. Improvement of insulin resistance by cyanidin 3-glucoside, anthocyanin from black beans through the up-regulation of GLUT4 gene expression. BMC Proceedings. 2011;5 (Suppl 8): P21. 22nd European Society for Animal Cell Technology (ESACT) Meeting on Cell Based Technologies. Vienna, Austria. May 15–18, 2011.
- Takikawa M, Inoue S, Horio F, Tsuda T. Dietary anthocyanin-rich bilberry extract ameliorates hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J Nutr. 2010;140:527–533.
- Kurimoto Y, Shibayama Y, Inoue S, et al. Black soybean seed coat extract ameliorates hyperglycemia and insulin sensitivity via the activation of AMP-activated protein kinase in diabetic mice. J Agric Food Chem. 2013;61:5558–5564.
- Mihaylova MM, Shaw RJ. The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy and metabolism. Nat Cell Biol. 2011;13:1016–1023.
- Sasaki R, Nishimura N, Hoshino H, et al. Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol. 2007;74:1619–1627.
- Wentworth JM, Naselli G, Brown WA, et al. Pro-inflammatory CD11c+CD206+ adipose tissue macrophages are associated with insulin resistance in human obesity. Diabetes. 2010;59:1648–1656.
- Guo H, Ling W, Wang Q, et al. Effect of anthocyanin-rich extract from black rice (Oryza sativa L. indica) on hyperlipidemia and insulin resistance in fructose-fed rats. Plant Foods Hum Nutr. 2007;62:1–6.
- Törrönen R, Sarkkinen E, Tapola N, Hautaniemi E, Kilpi K, Niskanen L. Berries modify the postprandial plasma glucose response to sucrose in healthy subjects. Br J Nutr. 2010;103:1094–1097.
- Törrönen R, Kolehmainen M, Sarkkinen E, Mykkänen H, Niskanen L. Postprandial glucose, insulin, and free fatty acid responses to sucrose consumed with blackcurrants and lingonberries in healthy women. Am J Clin Nutr. 2012;96:527–533.
- Törrönen R, Kolehmainen M, Sarkkinen E, Poutanen K, Mykkänen H, Niskanen L. Berries reduce postprandial insulin responses to wheat and rye breads in healthy women. J Nutr. 2013;143:430–436.
- Jayaprakasam B, Olson LK, Schutzki RE, Tai M-H, Nair MG. Amelioration of obesity and glucose intolerance in high-fat-fed C57BL/6 mice by anthocyanins and ursolic acid in Cornelian cherry (Cornus mas). J Agric Food Chem. 2006;54:243–248.
- Nizamutdinova IT, Jin YC, Chung JI, et al. The anti-diabetic effect of anthocyanins in streptozotocin-induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis. Mol Nutr Food Res. 2009;53:1419–1429.
- Sun CD, Zhang B, Zhang JK, et al. Cyanidin-3-glucoside-rich extract from Chinese bayberry fruit protects pancreatic β cells and ameliorates hyperglycemia in streptozotocin-induced diabetic mice. J Med Food. 2012;15:288–298.
- Adisakwattana S, Yibchok-Anun S, Charoenlertkul P, Wongsasiripat N. Cyanidin-3-rutinoside alleviates postprandial hyperglycemia and its synergism with acarbose by inhibition of intestinal α-glucosidase. J Clin Biochem Nutr. 2011;49:36–41.
- Akkarachiyasit S, Charoenlertkul P, Yibchok-Anun S, Adisakwattana S. Inhibitory activities of cyanidin and its glycosides and synergistic effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase. Int J Mol Sci. 2010;11:3387–3396.
- Zhang L, Li J, Hogan S, Chung H, Welbaum GE, Zhou K. Inhibitory effect of raspberries on starch digestive enzyme and their antioxidant properties and phenolic composition. Food Chem. 2010;119:592–599.
- Jayaprakasam B, Vareed SK, Olson LK, Nair MG. Insulin secretion by bioactive anthocyanins and anthocyanidins present in fruits. J Agric Food Chem. 2005;53:28–31.