CHAPTER
8
Glycine max (Soybean) Treatment for Diabetes S.L. Badole*, S.L. Bodhankar‡
PES’s Modern College of Pharmacy, Pune, India Bharati Vidyapeeth Deemed University, Pune, India
‡
1. INTRODUCTION Glycine max (L.) Merr. (soybean) is a subtropical plant native to southeastern Asia. Soybean has been a dietary staple in Asian countries for at least 5000 years. During the Chou dynasty in China, fermentation techniques were discovered that allowed soybean to be prepared in more easily digestible forms such as tempeh, miso, and tamari soy sauce. Tofu was invented in second-century China. Soybean was introduced to Europe in the 1700s and to the United States in the 1800s. Currently, Midwest U.S. farmers produce about half of the world’s supply of soybean. Soybeans are native to East Asia, but only 45% of soybean production is located there. The other 55% of production is in America. U.S.A. produced 75 million tons of soybean in 2000, of which more than one-third was exported. Other leading producers are Brazil, Argentina, Paraguay, China, and India (Joy et al., 1998). Scientific Classification Kingdom: Plantae Phylum: Magnoliophyta Class: Magnoliopsida Order: Fabales Family: Fabaceae Subfamily: Faboideae Genus: Glycine Species: G. max Botanical name: Glycine max (L.) Merr. Synonyms: G. gracilis, G. soja Common name: Soybean, Soya bean
2. BOTANICAL DESCRIPTION The plant: It may grow not higher than 20 cm (7.8 in.) or up to 2 m (6.5 ft) high. The pods, stems, and leaves are covered with fine brown or gray hairs.
Bioactive Food as Dietary Interventions for Diabetes http://dx.doi.org/10.1016/B978-0-12-397153-1.00008-1
#
2013 Elsevier Inc. All rights reserved.
77
78
S.L. Badole and S.L. Bodhankar
Leaves: Trifoliolate, having 3–4 leaflets per leaf. Leaflets are 6–15 cm (2–6 in.) long and 2–7 cm (1–3 in.) broad. The leaves fall before the seeds are mature. Flowers: Big, inconspicuous, self-fertile, the flowers are borne in the axil of the leaf and are white, pink, or purple. Fruit: A hairy pod that grows in clusters of 3–5; each pod is 3–8 cm long (1–3 in.) and usually contains 2–4 seeds (rarely more). Seeds: 5–11 mm in diameter. Soybeans occur in various sizes and in many hull or seed coat colors, including black, brown, blue, yellow, green, and mottled. The hull of the mature bean is hard, water resistant, and protects the cotyledon and hypocotyl (or ‘germ’) from damage. If the seed coat is cracked, the seed will not germinate. The scar, visible on the seed coat, is called the hilum (colors include black, brown, buff, gray, and yellow), and at one end of the hilum is the micropyle, or small opening in the seed coat, which allows for the absorption of water for sprouting (Joy et al., 1998).
3. GLYCINE MAX TREATMENT FOR DIABETES Many studies in humans and animals suggest that soy has beneficial effects in patients with diabetes mellitus. Soy flour was added to whole-durum meal in alloxan-diabetic hypercholesterolemic rats. The flour, with or without methionine, lowered the elevated plasma glucose, cholesterol, and lipid concentrations. Compared with a diet containing a mixture of animal and plant protein, a diet containing soy protein reduced the frequency and delayed the onset of diabetes. This finding suggests that the development of type 1 diabetes depends on the nature of the dietary protein (Atkinson et al., 1998). Ikeda and Sugano (1993) studied the effect of the interaction between the type of dietary protein and fat in rats with streptozotocin-induced diabetes. They observed significantly different interactions between the type of dietary protein (casein compared with soy) and fatty acid saturation in healthy and streptozotocin diabetic rats. In healthy rats, the linoleic acid desaturation index in liver microsomal phospholipids was significantly lower in rats fed soy than in those fed casein, but the reverse was true in diabetic rats. Mahalko et al. (1984) fed different sources of fiber to type 2 diabetic subjects for 2–4 weeks and observed a beneficial effect of soy hull on glucose tolerance, lipid indices, and glycated hemoglobin. The effect may have been due to polysaccharide, a nongel-forming fiber, in general rather than to other constituents of soy. In another study, it was observed that in obese subjects with type 2 diabetes, soy polysaccharide significantly reduced the increase in postprandial serum glucose and triacylglycerol concentrations. This effect appears to have been due to smaller increases in glucagon and pancreatic polypeptide and larger increases in somatostatin concentrations. There was no significant effect on serum insulin concentrations.
Glycine max (Soybean) Treatment for Diabetes
According to Hermansen et al. (2001), in type 2 diabetic subjects, soy protein with its associated isoflavones and fiber reduced LDL cholesterol, apolipoprotein B-100, and triacylglycerol as compared with a casein diet with cellulose but had no effect on glucose metabolism, as shown by the lack of change in HbA1C. Soy protein and genistein (one of the main isoflavones in soybean) supplements were reported to be beneficial in correcting hyperglycemia and preventing diabetic complications in streptozotocininduced diabetic rats (Lee, 2006). Increased isoflavonoid aglycones and small peptides resulting from the fermentation of soybean improved glucose-stimulated insulin secretion in islets of diabetic rats (Kwon et al., 2007). The antiamylase activity of soybean was shown to be associated with antioxidant activity and to phenolic mobilization during bioprocessing or sprouting (McCue et al., 2005). Soybean-derived dietary components may play an important role in these beneficial effects because soybean proteins are rich in arginine and glycine amino acids that are involved in insulin and glucagon secretion by the pancreas, respectively (Gannon et al., 2002). Soybean proteins improve the fasting glucose tolerance and peripheral insulin sensitivity in rats (Lavigne et al., 2000). Dietary soybean stimulates the activity of b-cells and prevents the development of hyperglycemia in streptozotocin-induced diabetic rats (Lee and Park, 2000). Dietary supplements with soy protein and isoflavones affected insulin resistance, glycemic control, and cardiovascular risk markers in postmenopausal women with type 2 diabetes (Jayagopal et al., 2002). Early studies in healthy human subjects showed that soy polysaccharides reduce postprandial glucose and triacylglycerol concentrations (Tsai et al., 1987), suggesting that the polysaccharides in soy may provide potential benefits in conditions of impaired glucose tolerance and hyperlipidemia. The beneficial effect of soy may also be due to the proteins it contains. Soy protein induced a lower postprandial insulin–glucagon ratio in healthy and hypercholesterolemic subjects than did casein (Sanchez and Hubbard, 1991). Lavigne et al. (2000) evaluated the effects of controlled feeding with various types of dietary proteins on glucose tolerance and insulin sensitivity in healthy male Wistar rats. The rats were fed isoenergetic diets containing casein, cod protein, or soy protein for 28 days. Rats fed cod and soy proteins had lower fasting plasma glucose and insulin concentrations than did the rats fed casein. After an intravenous glucose load (1.5 mL kg 1 body weight of 85% glucose in saline), the rats fed cod and soy proteins had lower incremental areas under the curves for glucose than did the rats fed casein, suggesting that cod and soy proteins improve glucose tolerance. Additionally, higher glucose disposal rates were observed in the rats fed cod and soy proteins than in the rats fed casein, indicating an improvement in peripheral insulin sensitivity. However, in the postprandial state, the lower plasma insulin concentrations observed in the animals fed cod and soy proteins may have been due to decreased pancreatic insulin release, increased hepatic insulin removal, or both. In a study in ovariectomized cynomolgus monkeys, soy protein significantly improved insulin sensitivity and glucose effectiveness compared with casein (Wagner et al., 1997). Furthermore, the animals fed with soy protein showed a decrease in aortic
79
80
S.L. Badole and S.L. Bodhankar
OH O
HO
O Diadzein OH OH
HO
O
O Genistein
Figure 8.1 Structures of some of the phytoconstituents of G. max. Reproduced from Hutabarat, L.S., Greenfield, H., Mulholland, M. 2000. Quantitative determination of isoflavones and coumestrol in soybean by column liquid chromatography. Journal of Chromatography A 88, 55–63.
cholesterol ester content, suggesting that dietary soy protein may provide additional cardiovascular benefits. Thus, it appears from these studies that soy-based diets may provide potential benefits in conditions associated with impaired glucose tolerance, hyperlipidemia, and reduced insulin sensitivity. Genistein and daidzein (Figure 8.1) lowered the insulin response to an oral glucose load. These results indicate the beneficial effects of isoflavones on excess body weight, hyperinsulinemia, and hyperlipidemia, which are the major cardiovascular risk factors commonly associated with obesity. In a study in genetically obese mice, Aoyama et al. (2000a) reported that soybean-protein isolate and its hydrolysis were more effective than was whey protein isolate and its hydrolysis in weight reduction; they act by lowering the perirenal fat pad weight and plasma glucose concentrations. This effect may be due to an active tetrapeptide present in soybean (Kagawa et al., 1996). The reduction in fat weight may be due to the increase in energy production and the activity of uncoupling protein in brown adipose tissue (Saito, 1991). The reduction in body fat by soybeanprotein isolate and its hydrolysate compared with casein was also observed in genetically obese yellow KK mice and in rats made obese by being fed a high-fat diet (Aoyama et al., 2000b). A 37-kDa protein in soybean appears to modulate insulin action on fat decomposition in vitro (Makino et al., 1988). Soybean-protein isolate and starch also lowered plasma glucose and insulin concentrations. Decreased total dissectible fat without significant loss of weight gain was observed in rats when casein was substituted isoenergetically with soybean protein in a starch-based diet (Baba et al., 1992).
Glycine max (Soybean) Treatment for Diabetes
Recently, Badole and Bodhankar (2009) reported that the aqueous extract of G. max (GM-AQE) (100, 200, and 400 mg kg 1, p.o.) showed peak antihyperglycemic effect at 4 h, indicating a lag period of 3–4 h before the peak effect was reached. The antihyperglycemic effect sustained until the 24th hour. The chronic study indicated that a period of 7 days is required for attaining a steady-state concentration of GM-AQE in the blood to reveal antihyperglycemic effects, and the antihyperglycemic effect was sustained even after withdrawal of GM-AQE for 7 days. The ability to maintain the antihyperglycemic effect of GM-AQE would be beneficial in clinical situations where the patient fails to take the drugs due to unavoidable circumstances. Chronic treatment for 35 days with GM-AQE in the tested doses brought about improvement in the body weights of alloxan-treated diabetic mice indicating its beneficial effect in preventing loss of body weight in diabetic mice. The ability of GM-AQE to protect against body weight loss seems to be due to its ability to reduce hyperglycemia. In OGTT, GM-AQE administration increased the glucose threshold at the 6th hour in both nondiabetic as well as diabetic mice. GM-AQE, but not petroleum or alcoholic extract (100 mg kg 1, p.o.), showed antihyperglycemic activity and prevented further loss in body weight in diabetic mice.
4. SUMMARY POINTS • G. max is economically one of the most important crops in the world as it is a major source of high-quality protein and vegetable oil for animal and human nutrition. • The seeds contain a number of components with health benefits, such as proteins, isoflavones (genistein, daidzein, and glycitein), coumestrol, phytate, saponins, lecithin, phytosterols, vitamin E, and dietary fiber. • Isoflavones have been reported to play an essential role in diabetes, hyperlipidemia, and cardiovascular diseases. • Dietary fiber plays an important role in the reduction of cholesterol levels in some hyperlipidemic individuals and in diabetes patients, it improves glucose tolerance.
REFERENCES Aoyama, T., Fukui, K., Nakamori, T., 2000a. Effect of soy and milk whey protein isolates and their hydrolysates on weight reduction in genetically obese mice. Bioscience, Biotechnology, and Biochemistry 64, 2594–2600. Aoyama, T., Fukui, K., Takamatsu, K., 2000b. Soy protein isolate and its hydrolysate reduce body fat of dietary obese rats and genetically obese mice (yellow KK). Nutrition 16, 349–354. Atkinson, M.A., Winter, W.E., Skordis, N., 1998. Dietary protein restriction reduces the frequency and delays the onset of insulin dependent diabetes in BB rats. Autoimmunity 2, 11–19. Baba, N., Radwan, H., Van Itallie, T., 1992. Effects of casein versus soyprotein diets on body composition and serum lipid levels in adult rats. Nutrition Research 12, 279–288. Badole, S.L., Bodhankar, S.L., 2009. Investigation of antihyperglycemic activity of Glycine max (L.) Merr. on serum glucose level in diabetic mice. Journal of Complement and Integratative Medicine 6, 1–15 (Article 4).
81
82
S.L. Badole and S.L. Bodhankar
Gannon, M.C., Nuttall, J.A., Nuttall, F.Q., 2002. The metabolic response to ingested glycine. American Journal of Clinical Nutrition 76, 1302–1307. Hermansen, K., Sondergaard, M., Hoie, L., 2001. Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care 24, 228–233. Ikeda, A., Sugano, M., 1993. Interaction of dietary protein and alpha-linolenic acid on polyunsaturated fatty acid composition of liver microsomal phospholipids and eicosanoid production in streptozotocin induced diabetic rats. Annals of Nutrition and Metabolism 37, 101–109. Jayagopal, V., Albertazzi, P., Kilpatrick, E.S., et al., 2002. Beneficial effects of soy phytoestrogen intake in postmenopausal women with type 2 diabetes. Diabetes Care 25, 987–990. Joy, P.P., Thomos, J., Mathew, S., Skaria, B.P., 1998. Medicinal Plants. Kerala Agriculture University, Aromatic and Medicinal Plant Research Station, Kerala pp. 73–74. Kagawa, K., Matsutaka, H., Fukuhama, C., 1996. Globin digest, acidic protease hydrolysate, inhibits dietary hypertriglyceridemia and Val-Val-Tyr-Pro, one of its constituents, possesses most superior effect. Life Sciences 58, 1745–1755. Kwon, D.Y., Jang, J.S., Hong, S.M., et al., 2007. Longterm consumption of fermented soybean-derived Chungkookjang enhances insulinotropic action unlike soybeans in 90% pancreatectomized diabetic rats. European Journal of Nutrition 46, 44–52. Lavigne, C., Marette, A., Jacques, H., 2000. Cod and soy proteins compared with casein improve glucose tolerance and insulin sensitivity in rats. American Journal of Physiology, Endocrinology and Metabolism 278, E491–E500. Lee, J.S., 2006. Effects of soy protein and genistein on blood glucose, antioxidant enzyme activities, and lipid profile in streptozotocin-induced diabetic rats. Life Sciences 79, 1578–1584. Lee, S.H., Park, I.S., 2000. Effect of soybean diet on the b-cells in the streptozotocin treated rats for induction of diabetes. Diabetes Research and Clinical Practice 47, 1–13. Mahalko, J.R., Sandstead, H.H., Johnson, L.K., 1984. Effect of consuming fiber from corn bran, soy hulls, or apple powder on glucose toleranceand plasma lipids in type II diabetes. American Journal of Clinical Nutrition 39, 25–34. Makino, S., Nakashima, H., Minami, K., 1988. Bile acid–binding protein from soybean seed: isolation, partial characterization and insulin stimulating activity. Agricultural and Biological Chemistry 52, 803–809. McCue, P., Kwon, Y.I., Shetty, K., 2005. Anti-diabetic and anti-hypertensive potential of sprouted and solid-state bioprocessed soybean. Asia Pacific Journal of Clinical Nutrition 14, 145–152. Saito, M., 1991. Effect of soy peptides on energy metabolism in obese animals. Nutrition Science Soy Protein 12, 91–94. Sanchez, A., Hubbard, R.W., 1991. Plasma amino acids and the insulin/glucagon ratio as an explanation for the dietary protein modulation of atherosclerosis. Medical Hypotheses 36, 27–32. Tsai, A.C., Vinik, A.I., Lasichak, A., Lo, G.S., 1987. Effects of soy polysaccharide on postprandial glucose, insulin, glucagon, pancreatic polypeptide, somatostatin, and triglyceride in obese diabetic patients. American Journal of Clinical Nutrition 45, 596–601. Wagner, J.D., Cefalu, W.T., Anthony, M.S., 1997. Dietary soy protein and estrogen replacement therapy improve cardiovascular risk factors and decrease aortic cholesteryl ester content in ovariectomized cynomolgous monkeys. Metabolism 46, 698–705.