CHAPTER ONE

                                                    INTRODUCTION

1.1 Background to the Study

Dietary control is vital in the management of diabetes. Reports from FAO (1998); WHO and FAO (2003) have shown that diets with low saturated fat, cholesterol and glycemic index as well as high contents of soluble fiber, vitamins and minerals are effective in the management of diabetes. Low glycemic foods contain sugars that digest and absorbed slowly into the blood and thus control blood sugar levels. The fiber-like substances such as gums and pectin reduced blood postprandial glucose levels (Jenkins et al., 1978; Ou et al., 2001) while diabetic subjects fed xanthan gum have lower fasting, postprandial serum glucose levels and total plasma cholesterol (Osilesi et al., 1985). Jenkins et al. (1978) reported that daily intake of 5–10 g of soluble fiber from different sources reduced serum cholesterol by 5–10%.  Fruits serve as one of the best sources of dietary fiber, minerals, Vitamins A, C and E and frequent intake of vegetables and fruits have demonstrated a lowered risk of diabetes, heart disease, hypertension, stroke and cancer (Southon, 2000; Wargovich, 2000). Fruits supply carbohydrates in the form of soluble sugars, cellulose and starch (Nahar et al., 1998) and serve as source of nutrient, appetizer and food supplement in a world faced with problem of food scarcity.

Diabetes mellitus (DM) is a worldwide endemic disease in terms of occurrence, cost of medical care, and general complications (King et al., 1998). The metabo­lism of protein, carbohydrate and fat are affected in diabetic conditions, resulting in hyperglycemia. DM complication is mainly associated with a high risk of coronary heart disease (Giugliano et al., 1996), atherosclerosis, stroke and peripheral vascular disease. The incidence of DM world wide, is projected to increase from 4% in 1995 to 5.4% by the year 2025 (Mohamed et al., 2006), with the utmost increases set to occur in the devel­oping countries of Africa, Asia and South America (WHO, 2008).

According to WHO (1994) and American Diabetes Association (2008), diabetes mellitus can be classified into insulin-dependent diabetes mellitus, IDDM (type 1 diabetes mellitus) and non- insulin- dependent diabetes mellitus, NIDDM (type 2 diabetes mellitus). Insulin-dependent diabetes mellitus is caused by cellular-mediated autoimmune damage to beta cells of the pancreas, accounts for about 5% to 15% of diabetic cases and occurs mostly in children or adolescents (Ranjan and Ramanujam, 2002). Genetics and environmental factors are implicated in the formation of IDDM. Administration of exogenous insulin is thus required to avert ketosis and preserve life (Lokesh and Amit, 2006). Non- insulin- dependent diabetes mellitus starts as insulin resistance, accounts for 85-95% of cases globally and occurs usually in adults of 40 years and above (WHO Regional Office for the South-East Asia, 2009). It is associated with hyperglycemia and glycosuria. The risk factors increases with age, lack of physical activity, obesity and impaired glucose tolerance.

Insulin resistance occurs when glucose is not properly utilized by the cells leading to high blood glucose in circulation. To maintain blood glucose level, the kidney excretes exess blood glucose through the urine and glucosuria occurs with increased excretion of water and sodium when blood glucose level exceeds the renal threshold (160 - 180 mg/L). The failure to use glucose by the body cells, results to increase appetite (polyphagia) (Robinson et al., 1986). The summary of the symptoms of diabetes is shown in Figure 1.

Figure 1: Overview of the most Significant Symptoms of  Diabetes

Source:  Cooke and Plotnick (2008)

Insulin resistance is associated with decreased glucose uptake and stimulation of muscle glycogen synthesis (Cline et al., 1999). In addition, alteration of  enzymatic activities like increased phosphatase activity and/or seryl phosphorylation of the insulin  receptor substrate by glycogen synthesis kinase 3 (GSK- 3), have also been reported in some cases of type 2 diabetes mellitus (Begum et al., 1991; Nadiv et al.,1994; Eldar-Finkelman and Krebs, 1997). Insulin resistance plays an important role in the etiology of many disorders including obesity, NIDDM, glucose intolerance, hypertension and other related disorders. It has been reported that autophosphorylation of insulin receptor kinase and subsequent phosphorylation of its principal substrate, IRS-1, are significantly lowered in insulin-responsive tissues of patient with severe obesity or NIDDM (Nadiv et al., 1992). Increased lipolysis and decreased lipogenesis occurred when there is a fall in circulated insulin leading to fatty acids release from adipose tissues and subsequently oxidized to ketone bodies in the liver. The rapid release of fatty acids into the blood leads to increase level of blood cholesterol and the formation of atherosclerosis (Khan and Ahmad, 1993). In diabetics, there is increase in excreted nitrogen through deamination, which is accompanied by cellular potassium excretion in urine when the muscle protein is broken down to support gluconeogenesis in the liver.

Of the several approaches applied, to lower and control the occurrence of diabetes, drug and diet therapies form the most popular approaches. The most common approach are the drug therapy with four distinct classes of oral hypoglycemic agents (biguanides, sulfonylureas, thiazolidinediones and alpha-glucosidase inhibitors) currently being recommended for use to treat NIDDM.  In dietary therapy, dietary modifications with adequate exercise are used to prevent excessive weight gain and obesity (Derek, 2001).  Intake of diets with low total and saturated fat, limited protein with replacement by complex carbohydrate and/or mono unsaturated fatty acids are the recommended diets for type 2 diabetes patients. Controlled diets will improve the metabolic control in diabetic subject and lower the risk of diabetes complications (Griver and Henry, 1994).

A large number of plants with hypoglycemic activity have been reported in different animal models. Aloe vera, Acacia arabica, Allium sativum L., Bombax ceiba L., Allium cepa, Brassicajuncea (L.) Cassia auriculata L., Caesalpinia bonducella (L.) and Musa sapientum L. are some of the scientifically validated antidiabetic plants (Modak et al., 2007).

Plant of Study

Chrysophyllum albidum (Linn), commonly called African star apple is a forest tree species of Sapotaceae family (Figure 2). It is widely distributed in Nigeria, Niger Republic and Uganda (Bada, 1997). C. albidum has various ethno-medicinal uses (Dalziel, 1937; Amusa et al., 2003) and across Nigeria, it is locally called ‘‘agbalumo’’ in South Western Nigeria and “udara” in South Eastern Nigeria.

Figure 2: Chrysophyllum albidum Tree 

Source: Orwa et al. (2009)

The fleshy pulp of C. albidum fruit is taken as snack, the seeds serve as a source of oil for various uses and the fruit is a good source of ascorbic acid (Adisa, 2000; Adepoju and Adeniji, 2012). C. albidum plants are rich in natural antioxidants and can thus support health by preventing oxidative stress related disease such as diabetics, cancer and coronary heart diseases (Burits and Bucar, 2002). The antioxidants content in vegetables and fruits has been associated with the diminished risk to chronic diseases by scavenging free radicals and prevent cells damage (Halliwell, 1994).

The antimicrobial and phytochemical screening of C. albidum seed cotyledon (Idowu et al., 2003; Okoli and Okere, 2010), leaves (Duyilemi and Lawal, 2009; Okoli and Okere, 2010; Kamba and Hassan 2011), root (Okoli and Okere, 2010), and stem bark (Adewoye et al., 2010; Kamba and Hassan 2011) have been investigated. In addition, the anti-hyperglycemic and hypolipidemic effects of C. albidum seed cotyledon ethanolic extract (Olorunnisola et al., 2008) and leaf ethanolic extract (Adebayo et al., 2010) have been reported. Adebayo et al., 2010, 2011a and 2011b, have reported the antiplatelet, antioxidant and hepatoprotective effects of C. albidum leaf while Onyeka et al. (2012) and Omotosho et al. (2013) reported the antifertility and antioxidant effects of C. albidum root bark and fruit juice.

Nwadinigwe (1982); Edem et al. (1984); Adisa (2000); Ige and Gbadamosi (2007); Ureigho (2010); Christopher and Dosunmu (2011); Oyebade et al. (2011); Adepoju and Adeniji (2012), have independently analyzed the nutritional contents of C. albidum pulp. Similarly, Ige and Gbadamosi (2007) analyzed the nutrient compositions of C. albidum fruit-peel (skin) and fruit juice. Ewansiha et al. (2011), analyzed C. albidum seed shell pericarp for its nutritional compositions while Ajewole and Adeyeye (1990), studied the physico-chemical characteristics and fatty acid composition of the seed. However, information on the nutrient contents of seed shell pericarp, fruit skin (peel) and fruit pulp of C. albidum are scanty in available literature. In addition, there is dearth of information on the efficacy of either of these edible portions of C. albidum fruit as remedy for the management of DM. Therefore, this study was design to investigate the nutrtitive and non-nutritive components and the antidiabetic potentials of the edible portions of C. albidum fruit.

1.2 Statement of the Problem

Diet has a vital role in the causes and control of several obesity-associated chronic diseases, such as diabetes and cardiovascular diseases. Current research has increased on studying individual foods to understand their specific role(s) and the mechanisms of action in the diminished risk to diseases in humans. Diabetes has emerged into a global epidemic, inspite of the recent search in new drugs to manage and prevent the condition; its prevalence continues to soar with increased risks and diagnosis in both adult and children (Ludwig and Ebbeling, 2001). In addition, many synthetic hypoglycemic agents such as biguanides, sulfonylureas, α-glucosidase inhibitors and insulin, commonly used for the treatment of diabetes are expensive and associated with serious side effects (Gupta et al., 2010). Sulfonylureas (e.g., glibenclamide) cause severe hypoglycemia, biguanides (e.g., metformins) are unsafe for patients with kidney problem, while α-glucosidase inhibitors cause dose-related malabsorption, flatulence and abdominal bloating (Codario, 2005). In addition, these hypoglycemic agents are not effective in the control of hyperlipidemia condition, which usually accompanies the incidence of diabetes (Derek, 2001). These associated problems with the synthetic oral anti-diabetic agents in terms of inefficacy, non-safety coupled with the emergence of the disease into a global epidemy have necessitate the search for more efficient alternatives with little or no side effect (Ranjan and Ramanujam, 2002). The plant kingdom, thus become a target for the search to develop indigenous, inexpensive botanical sources by multinational drug and biologically active lead compounds (Evans, 1996).

Since ancient times, medicinal plants with various active principles and properties have been used by laymen and physicians to cure a variety of human diseases such as coronary heart disease, diabetes and cancer (Havsteen, 1984; Middleton et al., 2000). Medicinal plants offer exciting opportunity to develop them into novel therapeutics due to their multiple beneficial effects as manipulating carbohydrate metabolism by various

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