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Diabetes Mellitus Type 2 and Functional Foods of Plant Origin Manju Pathak* Amity University, Noida, Uttar Pradesh, India Received: May 12, 2014
Revised: June 16, 2014
Accepted: July 05, 2014
Abstract: Diabetes is the common, exponentially growing, serious human health problem existing on this globe. Risk factors like genetic predisposition, lack of balanced diet, inappropriate and lethargic lifestyle, overweight, obesity, stress including emotional and oxidative and lack of probiotics in gut are the factors either in isolation or in synergy predisposing Diabetes. High blood sugar is a common symptom of all types of diabetes mellitus and the physiological cause of diabetes is lack of hormone Insulin or resistance in function faced by insulin. Low levels of Insulin causes decreased utilization of glucose by body cells, increased mobilization of fats from fat storage cells and depletion of proteins in the tissues of the body, keeping the body in crisis. The functional foods help achieving optimal physiological metabolism and cellular functions helping the body to come out of these crises. The mechanism of the functional foods is envisaged to act via optimizing vitamins, minerals, essential amino acids, prebiotics and probiotics. This paper reviews role of functional foods of plant origin in the regulation of blood sugar in type 2 diabetes mellitus and also discusses some vital patents in this area. The article aims at creating awareness about key food ingredients in order to prevent most acute effects of diabetes mellitus and to greatly delay the chronic effects as well.
Keywords: Antidiabetic, diabetes management, functional foods, insulin, nutraceuticals, type-2 diabetes. INTRODUCTION The care and prevention of Type 2 diabetes mellitus (T2DM); the chronic human health problem, is required at the present time [1]. This metabolic disorder is the causative factor for various other physiological disorders like cardiovascular problems, hypertension, arthritis, vision problems, bone problems causing significant health, social and economic load on the human society [2, 3]. The increasing trend in the disease indicates that the problem is the outcome of some specific environmental conditions which did not exist before. It also reflects the changes in lifestyle and diet of human beings. Pharmaceutical interventions alone are not very promising in the regulation of high blood sugar. The dosage of medicines apparently increases with the increase in the time indicating the worsening of the disease. Appropriate diet and certain bioactive of plant origin have been observed beneficial in regulating the high blood sugar in T2DM patients. Functional foods are the designer foods that provide therapeutic benefits. Diabetes Mellitus has been characterized as Type-1, Type-2 and Gestational. Some people show high fasting blood sugar levels but expected postprandial levels; while for some fasting blood sugar is not very high but the postprandial is beyond limits. Hence in T2DM, fasting and postprandial blood glucose levels should remain in limits for optimal physiological conditions. HYPERGLYCAEMIA AND INSULIN For prevention of T2DM, balanced diet with essential vitamins, minerals and amino acids are required. Many studies *Address correspondence to this author at the Amity University, Noida, Uttar Pradesh, India; Tel: +918130312878; E-mail:
[email protected] 1872-2083/14 $100.00+.00
showed beneficial effect of dairy products in reducing T2DM and other associated health disorders like obesity and cardiovascular complications [4, 5 and 6]. Whey protein was observed to enhance insulin secretion and reduce postprandial blood sugar if ingested with carbohydrates in T2DM patients [7, 8]. The insulinogenic effect was observed due to release of incretin and the presence of specific amino acids as leucine, threonine, isoleucine and valine in plasma after ingestion of whey protein [9]. Insulin secretion is stimulated after ingestion of essential amino acids [10, 11]. Essential amino acids can be obtained from various other sources including sprouts of some legumes and cereals easily. High Mg in raw fruit peel and leaves of P. guajava was observed providing antidiabetic benefits in alloxan induced diabetic rats [12, 13]. Strictinin, isostrictininpedunculagin are some flavonoid glycosides used for stimulation of insulin secretion in T2DM patients. The FAO and WHO suggested intake of low glycemic foods for the glucose intolerant diabetes individuals [14]. A Linear correlation was observed between glycemic index (GI) and insulinemic index [15]. In T2DM hyperglycemia and hyperinsulinemia are the outcome of resistance faced by hormone insulin at cellular level [16]. The intake of high glycemic foods causes increased demand of insulin and the prolonged demand of high insulin causes hyperinsulinemia [17]. Hence the low GI foods are desirable for persons with hyperinsulinemia and diabetes [18]. Proteins affect the glucose metabolism; different proteins affect differentially the metabolism in humans. Some amino acids are effective in stimulating insulin secretion [19]. Insulin secretion is enhanced by Glucose- dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) which is released after food intake. Protein rich food enhances release of GIP in healthy individuals and T2DM [20]. © 2014 Bentham Science Publishers
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β- Cells of pancreas secrete hormone insulin which further manages glucose homeostasis in humans. Abnormal physiological state of β- Cells in pancreas usually leads to Diabetes Mellitus; however the abnormal state is yet to be understood. HYPERGLYCAEMIA AND VITAMINS Vitamins play a very important role as they are the precursors of various co factors and its uptake by cell is promoted by Insulin but inhibited by hyperglycemia. In Insulin dependent diabetes mellitus (IDDM) patients if the plasma ascorbic acid is not supplemented with external insulin then the cellular hyperglycemia would results into tissue scurvy. The severity of disease in IDDM patients result either from accumulation of intracellular sorbitol or the glycooxidation of proteins in isolation or in synergy. The level of sorbitol depends upon the supplementation of vitamin C in such patients. Vitamin C acts as an antioxidant, causes inhibition of aldose reductase and hence regulates high blood sugar. To achieve optimum blood sugar in T2DM and IDDM patients’ supplementation of vitamin C is required [21]. Vitamin C is the scavenger of cellular free oxygen radicals and being structurally similar to glucose, replaces glucose in many biochemical reactions; hence it is effective in prevention of glycosylation of proteins. In guinea pigs, it also causes regulation of catabolism of cholesterol to bile acids and thereby plays an important role in the regulation of concentration of lipids. Vitamin C levels are low and free oxygen radicals are high in diabetes patients. Vitamin C supplementation has been observed beneficial in regulation of high blood sugar in T2DM [22]. Diabetes mellitus patients usually suffer from lipid metabolism disorders showing increased triglycerides levels and decreased HDL levels [23]. Obesity and obesity related diseases like hypertension, diabetes and cancer are the major public health problem today. Factors exactly regulating physiological parameters like increased CRP level and generalized inflammation, with a common symptom of high blood sugar still remain a secret. Exploring this secret is one of the major challenges. But at the same time preventing and managing the disease is another important task in front of mankind. An invention suggests managing blood sugar with soybean sprouts. Soybeans are rich in lysine, leucine, isoleucine, phenylalanine, calcium and phosphate. [24]. Enzymes produced during germination converts starch into more digestible maltose, and the vitamins and minerals enhance significantly. Germination in soybean seeds significantly increased the vitamin C content from 2mg/kg to 3.2 mg/kg [25]. Germination also decreases anti-nutritional factors such as trypsin inhibitor in the seeds [26]. It is known that legumes contribute significantly towards protein, minerals and vitamins and these micronutrients increase significantly during germination. Development of functional foods with germinated grains and pulses would help in fighting degenerative diseases, like T2DM, associated with today’s changing lifestyles and inappropriate diet. A fat tissue in human body does the job of immune and endocrine functions besides storing energy through various adipocytokines like visfatin, leptins, resistin and adiponectin. Some cytokines like TNF- α, IL-6, MCP-1 (CCL-2), IL-1is released by inflammatory cells and infiltrates into fat cells helps in immune and endocrine functions. Vitamin B manages NAD and NAD is the important co enzyme playing vital role in
Manju Pathak
metabolism by acting as oxidant and reductant time to time in the metabolic pathways. They help in maintaining the cellular redox potential. NAD homeostasis depends upon free oxygen radicals; these radicals further leads to cellular reactive oxygen species in many diseases like diabetes, cancer, neurodegenerative diseases, and inflammatory syndrome. The cellular redox potential depends upon the absolute concentration of pyridine dinucleotide and their ratio of oxidized and reduced state in the cell NAD/NADH and NADP and NADPH [27]. GERMINATION: A KEY PROCESS IN TURNING SEEDS TO FUNCTIONAL FOODS Germination is a natural cost effective bioprocess of the seeds where various biochemical ingredients increase in amount while some are synthesized to support the healthy growth of baby plant. Micronutrients enhance insulin secretion and function. Supplementation of vitamins niacin and niacin amide, vitamin C, vitamin E, Zinc, vanadium and chromium are found beneficial in regulation of high blood sugar [28]. A study was carried out to investigate the presence of insulin-like proteins based on immuno-recognition with anti-insulin antibodies in raw seeds and in the seeds germinated for various intervals of time of three edible legumes namely Glycine max (soybean), Vigna radiata (moong bean) and Vigna unguiculata (cow pea), hypothesizing the expression of insulin like proteins exclusively during seed germination that involves sugar metabolism and transport and cell proliferation. Consistent with this hypothesis, all germinated seed samples tested positive for the presence of insulin-like proteins whereas raw seed samples did not show any trace of these proteins in six trials of Enzyme Linked Immunosorbent Assays (ELISA) performed. Further, the levels of insulin changed with the period of germination indicating that there are different roles and regulatory mechanisms for these proteins and the expression of these proteins are highly regulated during the process of germination which is a critical plant development period. Maximum levels of insulin is observed in 72 h germinated seeds of G. max and in the 96 h germinated seeds of V.radiata and V. unguiculata. The results demonstrate that insulin-like proteins are expressed during germination and hence suggest that these proteins might have an important physiological role in germination. This opens up a prospect of analyzing the hypoglycemic activity of these proteins compared to insulin in animals, subsequently leading to the development of functional foods for treating diabetes. [29]. Many studies supported the increase in quantity and quality of proteins during germination along with micronutrients and fiber. Process of germination reduces tannins and phytic acid content of the seeds which enhances absorption of minerals [30]. The process of germination induces synthesis of prebiotics in the seeds and also improves the texture and flavor [31]. In Japan process of germination was applied to brown rice to increase the nutrients and softening the texture. Presently consuming germinated grains and legumes in regular diet is not very common in Indian population [32]. The germination depends upon the quality and vigor of the seeds [33]. Seeds optimized for bioavailability through optimized germination time can be utilized as functional foods for the management of diabetes mellitus and various other associated health problems.
Diabetes Mellitus Type 2 and Functional Foods of Plant Origin
PROBIOTIC THERAPY FOR THE PREVENTION AND CONTROL OF T2DM Probiotics like Lactobacilli and Bifidobacterium have been shown as an effective biotherapeutics in animal models in vivo and in vitro [34]. Functional foods optimized with such probiotics can be the cost effective therapeutics in management of T2DM [35]. Germinated seed of Lentils (Lens culinaris), Mung beans (Vigna radiata) and Peanut (Arachis hypogeal) were found rich in probiotics [36]. Hence germination optimized sprouts of above seeds could enrich the gut with probiotics. RECENTLY ISSUED PATENTS TO FUNCTIONAL FOODS Diabetic nutritional product having controlled absorption of carbohydrates was described by Gregory J. Wilbert, Harry L. Greene, Kim R. Keating, Yung-Huiung Lee [37]. This invention relates to a nutraceutical for T2DM. The carbohydrate component of this nutraceutical consists of sucrose, glucose and corn starch. Karen A. Cashmere, Elizabeth M Besozzi invented a liquid nutritional blend containing fiber, low glycemic carbohydrates, proteins, vitamins and minerals for T2DM [38]. Francis Audry, Daniel Evard, Etienne Grasset, Veronique Jaussan formulated a liquid nutritional composition consisting of lipids, proteins and glucides [39]. Philip Laughlin, John Alexander, A. Reza Kamarei and others have developed an enteral diet for providing nutrient to T2DM patients. [40]. A blood sugar regulating product was invented by Manju Pathak by germinating the soybean seeds. [41]. The invention in this patent included the soaking of the raw soybeans followed by germination of the seeds, followed by peeling off the seed coats and then drying the germinated seed at temperature between 10º C to 95° C ,the dried seeds were then grinded in fine powder. The invention claims the synthesis of PI3K (phosphatidyl inositol 3 kinase) and increase in quantity of tyrosine dihydrogenase, myoinositol dehydrogenase during early seed germination. Tarrant Laurence J Berlowitz, Robert J Nicolosi, Frank Orthoefer prepared a functional food for diabetics. [42]. 王介人, 胡献安, 舒万淑, 郜敏, 王京 formulated coffee type healthful tea in 1995 for blood sugar regulation [43]. 刘金忠 described a diet formula in his invention for regulating the blood sugar and a processing technology thereof, in particular to the functional health care food industry. This diet formula was a functional diet food which was produced by utilizing coarse grains, nuts, dried fruits, yams, wild vegetables and non- toxic Chinese herbal medicines through the scientific formula; which is developed to lower and regulate the blood sugar value against a plurality of defects of the functional health care products on the market. The functional food is prepared by the procedures of grinding the raw materials into powder, soaking, filtering, weighing for compatibility, mixing, flour mixing, shaping, cooking, packaging, sterilization, etc [44]. Glycoprotein with antidiabetic, antihypertensive and antiobesity from Grifola Frondosa was described by CunZhuang, HirokazuKawagishi and Harry G. Preuss [45]. Stacy J. Bell and Judith Shabert invented a nutritional supplement for patients with T2DM for lipodystrophy [46]. Their invention relates to a nutritional product
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which aids in the improvement of platelet aggregation. The nutritional supplement in this invention comprises of low GI carbohydrate, proteins and fats. Bradley T. MacDonald developed a powdered food for blood sugar management [47]. Glucose metabolism enhancer was described and claimed by a Chinese inventor 哈里斯韦恩 [48]. The invention discloses an advanced glucose metabolism enhancer (or therapeutic food or preparation), mainly comprising trioligopeptidelipoate, standardized high-valence activator, vitamins and mineral support. The supplement was determined by scientific research and clinical research to be composed of high-quality specific nutritive components required for maintaining normal blood sugar degree and insulin sensitivity. Fortified Food Products; nutritional Supplement for improving glucose metabolism was invented by Rick W Womack [49]. His invention provides a nutritional supplement and method for administering nutritional supplement that comprises a source of chromium, Gymnema sylvestre and lipoic acid. The inventor describes that this product prevents accumulation of nutrients in the body. Dusan Miljkovic, Zbigniew pietrzkowski prepared malted barley extract for activating adenosine 5'-monophosphate-activated protein kinase [50]. Pradeep Poddar, Henry Hidell and CE Agro invented the process of Trivalent Chromium and Boron fortifying composition supplement. The invention provided nutrient fortifying composition for food products. More particularly the invention provided chromium and boron fortifying composition comprising boron source, trivalent chromium source, copper ion source, class II preservative and acidity regulator. The invention further provided a hydration supplement and a fortified water beverage to supplement the deficiencies of chromium and boron in humans [51]. CURRENT AND FUTURE DEVELOPMENTS Diabetes is the physiological state of the cell where glucose is not metabolized efficiently and therefore the level of glucose exceeds in the blood. The high concentration of glucose is bound to increase the viscosity of the blood and thereby increase in the osmotic pressure on the walls of the blood capillaries which further causes number of health complications including retinopathy. The problem is understood but its genesis is not completely understood yet. There are two aspects which require focused effort; one in management of high blood sugar in T2DM and second in understanding the mechanism involved in genesis of high blood sugar to prevent its future development in non diabetic individuals. The present review deals with first aspect. People with high blood sugar are prone to develop deficiency in some minerals like potassium, zinc and magnesium [52]. T2DM at present requires combinational therapy. The combinations of sulfonylurea with alpha glucosidase inhibitor, troglitazone,metformin is in clinical use presently. Similarly combination of metformin with insulin and troglitazone is also in use at present. All these drugs are derivatives of plants as in case of metformin, a biguanide derived from the leaves of legume plant Galegaofficinalis [52]. An alphaglucosidase inhibitor termed as Salacinolis is extracted from the roots of Salaciareticulata [53]. The leaves of Cryptolepissanguinolenta were used for the extraction of an indoloqui-
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nolene alkaloid termed as Cryptolepine [54]. Products derived from plants parts of Pterocarpusmarsupium, Ficusbengalenesis, Gymnemasylvestre, Momordicacharantia, Tinosporacordifolia, Allium cepa, Trigonella foenumgraecum, and Brassica juncea are being used in the management of T2DM [55, 56]. The term Nutraceuticals is coined by the Foundation for Innovation in Medicine in 1991. Zeisel in 1999 differentiated nutraceuticals from whole foods on the basis of presentation of non food matrix made from isolated bioactive compounds [57]. Folate and folic acids are vitamins of B group whose deficiency causes macrocytic anemia and increased levels of homocysteine. Plasma concentration of homocysteine in T2DM correlates with age and creatinine levels [58]. Probiotic bacteria; Lactobacillus and Bifidobacterium produces folate [59]. After realizing potential relevance of probiotics as microbial pharma nutrition their ability to produce folate has been intensively investigated in many Lactobacillus isolates from a variety of origins including human gastrointestinal tract. The realization that probiotics are associated with bio processed legume seeds [36]. Recently the genome sequence of many Lactobacillus isolates provided the knowledge of folate biosynthesis by these bacteria [60]. A probiotic composition comprising the powders of one or more dried seeds and strains from fermented foods can be incorporated in multiple nutraceuticals and foods to enhance the therapeutically effective micronutrients like folate content, vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, calcium, potassium, magnesium, phosphate, iodine, copper, manganese source, molybdenum, zinc, one or more tocopherols, lycopene, one or more carotenoids, one or more flavonoids, biotin, inositol, choline, one or more essential amino acids to enrich cellular environment and to provide holistic health. The market of functional foods for various health claims amounts to about € 7 billion. Functional foods and nutraceuticals of plant origin undoubtedly have pioneered the market due to its cost effectiveness, safer utility and therapeutic efficacy particularly in high blood sugar regulation and management of T2DM. But the taste, texture and form of the product were the prime factors deciding the growth in market depending on the demography.
Manju Pathak
ACKNOWLEDGEMENTS I acknowledge type 2 diabetes volunteers who inspired me to this article. REFERENCES [1] [2] [3] [4]
[5] [6] [7]
[8]
[9]
[10] [11] [12] [13]
[14] [15]
CONCLUSIONS We need to explore our foods with regard to its glycemic and insulinotropic response. An appropriate diet may be effective in regulating the blood sugar. Many functional foods till now have been reported for lowering blood sugar, even then the epidemic of T2DM is increasing. A wise scientific screening of functional foods and their proper awareness in the population is the need at present. We need to reach the general population to overcome the diabetes epidemic.
[16] [17]
[18] [19]
CONFLICT OF INTEREST DISCLOSURE
[20]
I certify that all the statements made in the article are correct to best of my knowledge. I also declare that I have no conflict of interest to declare.
[21]
Information regarding diabetes care, prevention and cure is available at http: //www.idf.org/diabetesatlas/ (The Diabetes Atlas 2006). de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: A metaanalysis. Psychosom Med 2001; 63: 619-30. Jacobson AM. Impact of improved glycemic control on quality of life in patients with diabetes. Endocr Pract 2004; 10: 502-8. Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi F. Dairy consumption is inversely associated with the prevalence of the metabolic syndrome in Tehranian adults. American Journal of Clinical Nutrition 2005; 82: 523-530. Pfeuffer M, Schrezenmeir J. Milk and the metabolic syndrome. Obes Rev 2007; 8: 109-118. Jauhiainen T, Korpela R. Milk peptides and blood pressure. The Journal of Nutrition 2007; 137: 825S-829S. Frid AH, Nilsson M, Holst JJ, Bjorck IM. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects. American Journal of Clinical Nutrition 2005; 82: 69-75. Nilsson M, Stenberg M, Frid AH, Holst JJ, Bjorck IM. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. American Journal of Clinical Nutrition 2004; 80: 12461253. Nilsson M, Holst JJ, Bjorck IME. Metabolic effects of amino acid mixtures and whey protein in healthy subjects: studies using glucose-equivalent drinks. American Journal of Clinical Nutrition 2007 ; 85: 996-1004. Noguchi Y, Nishikata N, Shikata N, et al. Ketogenic essential amino acids modulate lipid synthetic pathways and prevent hepatic steatosis in mice. PLoS One 2010; 5: e12057. Luhovyy BL, Akhavan T, Anderson GH. Whey proteins in the regulation of food intake and satiety. Journal of the American College of Nutrition 2007; 26: 704S-712S. Rai PK, Rai NK, Rai AK, Watal G. Role of LIBS in elemental analysis of P. guajava responsible for glycemic potential. Instrum Sci Tech 2007; 35: 507-22. Maryuma Y, Matsuda H, Matsuda R, Kubo M, Hatano T, Okuda T. Study on Psidiumguajava L. (I). Antidiabetic effect and effective components of the leaf of Psidiumguajava L. (Part I) Shoyakugaku Zasshi 1985; 39: 261-9. Jauhiainen T, Korpela R. Milk peptides and blood pressure. The Journal of Nutrition 2007; 137: 825S-829S. Van Loon LJ, Saris WH, Verhagen H, Wagenmakers AJ. Plasma insulin responses after ingestion of different amino acid or protein mixtures with carbohydrate. American Journal of Clinical Nutrition 2000; 72: 96-105. Rosen LA, Silva LO, Andersson UK, et al. Endosperm and whole grain rye breads are characterized by low post-prandial insulin response and a beneficial blood glucose profile. Nutr J 2009; 25: 42. Solerte SB, Fioravanti M, Locatelli E, et al. Improvement of blood glucose control and insulin sensitivity during a long-term (60 weeks) randomized study with amino acid dietary supplements in elderly subjects with type 2 diabetes mellitus. American Journal of Cardiology 2008; 101: 82E-88E. Will JC, Byers T: Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev 1996; 54: 193-202. Simom JA. Vitamin C and cardiovascular disease: a review. J Am CollNutr 1992; 11 : 107-25. Ginter E: Ascorbic acid in cholesterol metabolism and in detoxification of xenobiotic substances: the problem of optimum vitamin C intake. Nutrition 1989; 5: 369-374. Evans RM, Currie L, Campbell A: The distribution of ascorbic acid between various cellular components of blood in normal individuals, and its relation to the plasma concentration. Br J Nutr 1982; 47: 473-482.
Diabetes Mellitus Type 2 and Functional Foods of Plant Origin [22] [23] [24] [25] [26] [27] [28] [29]
[30] [31]
[32]
[33]
[34] [35]
[36] [37] [38] [39] [40]
Errikson J, Kahvakka A. Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab 1995; 39 : 217-23. Battisi WP, Palmisano J, Keane WE. Dyslipidemia in patients with type 2 diabetes: Relation between lipids, kidney disease and cardiovascular disease. ClinChem Lab Med 2003; 41: 881-91. Manju Pathak. Soaked and Germinated Soybean Seeds for Blood Sugar Control. Natural Product Radiance 2005; 4: 353-448. Victoria A. Jideani and Felix C. Onwubali. Optimisation of wheatsprouted soybean flour bread using response surface methodology. African Journal of Biotechnology 2009; 8: 6364-6373. Hallén E, bano_lu, Ainsworth P. Effect of fermented/ germinated cowpea flour addition on the rheological and baking properties of wheat flour. J. Food Eng. 2004; 63: 177-184. Uwaegbute AC, Iroegbu CU, Eke O. Chemical and sensory evaluation of germinated cowpeas (Vignaunguiculata) and their products. Food Chem 2000; 68: 141-146. Magni G, Orsomando G. Enzymology of mammalian NAD metabolism in health and disease 2008; 13: 6135-54. Manju Pathak and Danik M. Martirosyan. Immuno detection and quantification of Insulin-Like antigens in Sprouts: development of an efficient functional food. Functional Food in Health and Disease 2011; 11: 492-507. Sangronis, E., Rodriguez, M., Cava, R. and Torres, A. Protein quality of germinated Phaseolus vulgaris. European Food Research and Technology 2006; 222: 144-148. Vidal-Valverde, C., Frias, J., Sierra, I., Blazquez, I., Lambein, F. and Kuo, Y. New functional legume foods by germination: effect on the nutritive value of beans, lentils and peas. European Food Research and Technology 2002; 215(6): 472-477. Ghavidel, R.A. and Prakash, J. The impact of germination and dehulling on nutrients, anti nutrients, in vitro iron and calcium bioavailability and in vitro starch and protein digestibility of some legume seeds. LWT 2007; 40: 1292-1299. El-Adawy, T.A., Rahma, E.H., El-Bedawey, A.A. and El-Beltagy, A.E. Nutritional potential and functional properties of germinated mung bean, pea and lentil seeds. Plant Foods for Human Nutrition 2004; 58(3): 1-13. Panwar H, Rashmi HM, Batish VK, Grover S. Probiotics as potential biotherapeutics in the management of type 2 diabetes - prospects and perspectives. Diabetes Metab Res Rev 2013; 29: 103-12. Alokail MS, Sabico S, Al-Saleh Y, Al-Daghri NM, Alkharfy KM, Vanhoutte PM, McTernan PG. Effects of probiotics in patients with diabetes mellitus type 2: study protocol for a randomized, double-blind, placebo-controlled trial. Trials 2013; 14: 621514-195. Manju Pathak. Germinating Seeds: Source of Probiotics. World Applied Science Journal 2013; 26: 224-231. Gregory J. Wilbert, Harry L. Greene, Kim R. Keating, YungHuiung Lee. Diabetic nutritional product having controlled absorption of carbohydrate. US 5776887 A, 1995. Karen A. Cashmere, Elizabeth M Besozzi. Liquid nutritional formula for glucose intolerance. US4921877 A, 1990. Francis Audry, Daniel Evard, Etienne Grasset, Veronique Jaussan. Liquid nutritional compositions comprising slowly absorbed glucides. US5292723 A, 1994. Philip Laughlin, John Alexander, A. Reza Kamarei, Robert P. Dobbie, Paul Lin, Shen-Youn Chang, Shekhar Reddy, Etienne Grasset, Christian Melin. Enteral diet and method for providing nutrition to a diabetic. US5470839 A, 1995.
Recent Patents on Biotechnology, 2014, Vol. 8, No. 2 [41] [42] [43] [44] [45] [46]
[47]
[48] [49] [50] [51]
[52] [53] [54]
[55]
[56] [57] [58] [59] [60]
5
Manju Pathak. Blood sugar regulating agent comprising a natural dry product derived from soya bean seeds alone or in a mixture and preparation thereof. IN231606, WO 2004096250 A1, 2003. Tarrant Laurence J Berlowitz, Robert J Nicolosi, Frank Orthoefer. Nutritious food preparations and methods for making them. WO 1998003084 A1, 1998. 王介人, 胡献安, 舒万淑, 郜敏, 王京. Coffee type healthful tea and producing method CN 1107012 A, 1995. 刘金忠. Food prescription for regulating blood sugar and processing technique thereof. CN101322552 B1, 2007. CunZhuang, HirokazuKawagishi and Harry G. Preuss. Solvent extraction from plant. US 7214778 B2, 2003. Stacy J. Bell and Judith Shabert. Nutritional supplement comprising low-glycemic index carbohydrate source, source of protein, source of fat, source of sterol and/or stanol, source of chromium, source of salicylic acid, and source of ginseng. US 6365176 B1, 2000. Bradley T. MacDonald. Powdered food supplement that is mixed with water to prepare a liquid drink for diabetic people in order to maintain proper nutrition and weight management, while controlling and stabilizing blood sugar levels. US6706697 B1, 2004. 哈里斯韦恩. A glucose metabolism enhancer. CN 102847159 A, 2011. Rick W Womack. Nutritional supplements for improving glucose metabolism. US 5730988 A, 1995. Dusan Miljkovic, Zbigniew pietrzkowski. Purified malted barley extract is administered for activating adenosine 5'-monophosphateactivated protein kinase. WO2004021980A3, 2008. Pradeep Poddar, Henry Hidell and CE Agro, Micheal Collete. Trivalent chromium and boron fortifying composition, a hydration supplement, and process for preparing the same. WO2012038985A2, 2010. Mooradian AD, Failla M, Hoogwerf B, Maryniuk M, Wylie-Rosett J. Selected vitamins and minerals in diabetes. Diabetes Care 1994; 17: 464-479. Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes Care 1989; 12: 553-564. Yoshikawa M, Murakami T, Shimada H, et al. Salacinol potent antidiabetic principle with unique thiosugarsulonium sulphate structure from the ayurvedic traditional medicine Salacia reticulate in Sri Lanka and India. Tetrahedron Lett. 1997; 38: 8367-8370. Luo J, Fort DM, Carlson TJ, et al. Cryptolepissanguinolenta: an ethnobotanical approach to drug discovery and the isolation of potentially useful new antihyperglycaemic agent. Diab Medicine 1998; 15: 367-374. Grover JK, Yadav S, Vats V. Medicinal plants of India with antidiabetic potential. J Ethnopharmacol2002; 81: 81-100. Zeisel, S. Regulation of “nutraceuticals”. Science (Washington, DC) 1999; 285: 1853-1855. Russo GT, Di Benedetto A, Giorda C et al. Correlates of total homocysteine plasma concentration in type 2 diabetes. Eur J Clin Invest 2014; 34: 197-204. Rossi M, Amaretti A, Raimondi S. Folate production by probiotic bacteria. Nutrients 2011; 3: 118-34. De crecy-Lagard V., El Yacoubi B, de la Garza RD, Noirie A, Hanson AD. Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations. BMC Genomics 2007; 8: 245.
