Abstract           

Nowadays there is a rapid rise in the occurrence of obesity, diabetes as well as its associated diseases.

Many synthetic products are presently in the market and even hospitals to inhibit alpha amylase activity but so expensive and end up producing a lot of unwanted effects such as damaging the liver and adrenal glands.

It is therefore of vital importance to investigate other natural sources that can be found in diets that will inhibit alpha amylase (lowering blood glucose by blocking carbohydrate digestion) thus producing little or no side effects.

This experimental study investigates the in vivo inhibitory action of Artocarpus heterophyllus (jack fruit) on amylase using beef fried rice and slices of bread as starch source. Twenty normal young adults were chosen for the experiment between the ages of 18-24years.

The experiment was carried out on two consecutive days where volunteers fasted overnight from 10pm and were fed in the morning from 8am and samples collected after 90minutes for analysis.

From the results obtained, the mean 90minutes postprandial blood glucose levels on both day 1 and 2 were 109.85 ± 15.75mg/dl and 109.25 ± 15.70mg/dl respectively with a mean difference of 0.6mg/dl (95% C.I = -8.022 – 9.22) which was statistically insignificant (t = 0.146, p = 0.886). Therefore Artocarpus heterophyllus (jack fruit) has no inhibitory action on amylase.

CHAPTER ONE

INTRODUCTION

1.1 BACKGROUND OF STUDY

Diabetes mellitus or simply diabetes is a chronic metabolic disorder of carbohydrate, lipid and protein metabolism characterized by hyperglycemia, glycosuria, hyperlipidemia, negative nitrogen balance and sometimes ketonemia due to insufficient or complete cessation of insulin synthesis or secretion and/or peripheral resistance to insulin action (Das et al, 2011).

It is an  independent risk factor for cardiovascular disease, and the risk is markedly increased in the presence of hypertension and also cause a large number of complications. There are two major types of diabetes mellitus – type 1 and type 2.

In type 1 diabetes, or insulin dependent diabetes mellitus, the body has little or no insulin secretory capacity and depends on exogenous insulin to prevent metabolic disorders and death.

In type 2 diabetes, a non-insulin dependent diabetes mellitus, the body retains some endogenous insulin secretory capability; however, their insulin levels are low relative to their blood glucose levels and/or there is a measure of insulin resistance.

Type 2 diabetes is the most prevalent form of the disease, accounting for 90-95% of cases (kuete et al, 2008). Some known risk factors of diabetes include obesity, sedentary lifestyle and a diet high in carbohydrate and fats and obesity being this risk factor is a frequent condition in developed (Flegal et al, 1998 and World Health Organization).

Diabetes mellitus is among the commonest non-communicable diseases in both developed and developing countries. The prevalence of type 2 diabetes mellitus is increasing worldwide, and it is projected that the total number of people with diabetes will rise from 366 million in 2011 to 552 million by 2030 (International Diabetes Federation, 2011).

Thus WHO projects that diabetes will be the 7th leading cause of death in 2030 (Mathers et al, 2006). The prevalence of obesity and type 2 diabetes is rapidly increasing around the world, and its growth has become a major challenge for health care professionals to combat (Hossain et al, 2007; Young, 2010).The epidemic of obesity is probably a result of increasing sedentary lifestyles combined with easily available palatable, energy dense food.

According to Obesity Society, lifestyle changes (increase physical activity and caloric restriction) and small amounts of weight loss in the range of 5-10% can prevent or delay the development of type 2 diabetes among high-risk adults.

Low caloric diets are very effective in promoting weight loss but long term results are very disappointing. It may be worsening of self-control and increase feeling of hunger during the diet.

There is a close association between obesity and type 2 diabetes (Gatineau et al, 2014). The likelihood and severity of type 2 diabetes is closely linked with Body Mass Index (BMI). People who are obese have a greater risk of diabetes seven times greater than those of healthy weight, with a threefold increase in risk for overweight people (Abdullah et al, 2010).

Also is known that body fat distribution is an important determinant of increased risk of diabetes, the precise mechanism of association remains unclear. It is also uncertain why not all people who are obese develop type 2 diabetes and why not all people with type 2 diabetes are obese (Eckel et al, 2011; Neeland et al, 2012).

The fundamental cause of type 2 diabetes is genetics and environmental factors. The immediate cause of obesity is net energy imbalance- the organism consumes more usable calories than it expands wastes or discards through elimination whereas the fundamental cause of obesity is unknown but presumably a combination of the organism’s genes and environment. Obesity plays an important role in the impairment of lipid and carbohydrate metabolism shown in high carbohydrate diets (Ibrahim et al, 2000).

Abdominal obesity also known as belly fat or clinically as central obesity, is excessive fat around the stomach and the abdomen. Thus children and teenagers can have it if either of their parents have abdominal obesity.

There is a strong correlation between central obesity and cardiovascular disease (Yusuf et al, 2004). Abdominal obesity has been linked to Alzheimer’s disease as well as other metabolic and vascular diseases (Krishnan et al, 2007). Central and visceral fat waist circumference shows a strong correlation with type 2 diabetes.

Central obesity is associated with statistically high risk of heart disease, hypertension, insulin resistance and type 2 diabetes mellitus (Westphal et al, 2008). With an increase in the waist ratio and overall waist circumference the risk of deaths increases as well (Cameroon et al, 2008).

Central obesity being a symptom of Cushing’s syndrome and also common in patients with Polycystic Ovary Syndrome (PCOS), it is as well associated with glucose intolerance and dyslipidemia which becomes a severe problem.  An individual’s abdominal cavity would generate elevated free fatty acid flux to liver.

The effect of abdominal adiposity does not just occur in those who are obese but also affects people who are non-obese and also contributes to the insulin sensitivity. Central obesity is known to predispose individuals for insulin resistance.

A group of hormones called Adipokines are secreted especially by the abdominal fat that may possibly impair glucose intolerance. Insulin resistance is a major feature type 2 diabetes mellitus and central obesity is correlated. Serum resistin levels directly correlate insulin resistance due to increased obesity (adiposity) (Ascensio et al, 2008).

50% of men and 70% women in the United States between the ages of 50 and 79 years now exceed the waist circumference threshold for abdominal obesity (Li et al, 2007). When comparing the body fat of men and women, it is seen that men have close to twice the visceral fat as that of pre-menopausal women.

Abdominal obesity is associated positively with coronary heart disease risk in women and men. There are sex dependent differences in regional fat distribution. It has been hypothesized that the sex difference in fat distribution may explain the sex difference in coronary heart disease.

Fat stored in the buttocks, thighs and hips in women is believed to be caused by female sex hormones. When women reach menopause, fat migrates from their buttocks, thighs and hips to their belly as the oestrogen produced by the ovaries declines.

Furthermore the Artocarpus heterophyllus (Jackfruit) is a species of tree of the mulberry family Moraceae. This plant of Artocarpus species have been used by traditional folk medicine in Indonesia which can be useful as anti-diabetic, anti-bacterial, anti-inflammatory, antioxidant and  anti-helminthics (Agung  et al,2015).

Fruits are important dietary components, and contain various bioactive constituents. Many of these constituents have been proven to be useful to manage and treat various chronic diseases such as diabetes, obesity, cancer and cardiovascular diseases (Samir et al., 2011).

The pathogenesis of diabetes mellitus and its complications is managed by insulin and oral administration of hypoglycemic drugs such as sulfonylureas and biguanides (Velraj et al, 2011) but on chronic usage produce side effects like hypoglycemic coma, cholesterol jaundice.

A permanent routine of exercise, eating healthier and consuming the same number or fewer calories than used will prevent and help fight obesity as well as diabetes.

In the presence of type 2 diabetes mellitus, a physician might instead prescribe metformin and thiazolidinediones as antidiabetic drugs rather than sulfonylureas derivatives. Thiazolidinediones may cause slight weight gain but decrease visceral but decrease visceral fat and therefore, may be prescribed for diabetics with central obesity (Fonseca, 2003).

This drug has been associated with heart failure and increased cardiovascular risk, so it has been withdrawn from the market in Europe by EMA in 2010.

Moreover, Body Mass Index (BMI) in both men and women can be calculated using the formula below;

Body Mass Index (BMI) = (Weight in Kg) / (Height in m2) = Weight in lb / Height in inches square * 703 (Champe et al, 2008).

The healthy range for the BMI is (19.5 – 24.9)kg/m2 and (25.0 – 29.9)kg/m2 are considered overweight and those with BMI equal or greater than 30 are said to be obese. Nearly two thirds of American adults are overweight and more than 36% are obese (Champe et al, 2008).

Moreover previous studies have been carried out in Cameroon wherein researchers were interested in finding possible treatments for obesity and diabetes. In 2008, Julius E. Oben and his colleagues conducted an experiment at the University of Yaounde on the use of Cissus quadragularis/Irvingia gabonensis combination in the management of weight loss (a double-bind placebo-controlled study). The experiment was carried out on 72 overweight and obese human subjects aimed at evaluating the effects of two formulations, Cissus quadragularis only and a Cissus quadragularis/Irvingia gabonensis combination on their weight loss.

Capsules containing the active formulations or placebo were administered twice daily before meals, no major dietary changes nor exercise were suggested during the study.

A total of serological and anthropomorphic measurements (fasting blood glucose level, LDL cholesterol, total plasma cholesterol, body weight, body fat, waist size)were taken at baseline and at 4,8 and 10 weeks. The Cissus quadragularis only showed significant reductions on all variables compared to the placebo group, the combination of Cissus quadragularis/Irvingia gabonensis resulted in even larger reduction.

However the experiment did not investigate the effects of Irvingia gabonensis only on blood glucose as well as it didn’t explain the possible mechanism of action of Irvingia gabonensis in reducing blood glucose level.

From previous knowledge, it is known that alpha amylase enzyme is responsible for the digestion of carbohydrates to produce sugars which are then absorbed into blood. Thus inhibiting this enzyme therefore prevents carbohydrates digestion and in turn reduces blood glucose level as less glucose is absorbed into blood.

But still there is no experiment that has been conducted in Cameroon to investigate the anti-diabetic effect of Artocarpus heterophyllus whereby the fruit act as a starch blocker via the inhibitory effect on alpha amylase hence decreasing post prandial glucose. Instead in 2013 a similar experiment was conducted at the University of Buea by Tala Kuh Lazzarus under the supervision of Michael A.G. Boyo on the in vivo inhibitory effect of Irvingia gabonensisin overweight young males.

The aim of the experiment was to investigate the inhibitory effect of “ogbono’’seeds on alpha amylase activity in vivo and the effect of “eru’’ on alpha amylase. Twenty overweight males within the age of 19-26 were selected for the experiment.

The experiment was carried out on two consecutive days with the subjects fasted overnight and fed at 8 am on each day. On day 1, subjects were fed with 500g of Manihotesculenta(“kumkum’’) and 250g of “ogbono’’ soup whereas on day 2, subjects were fed with 500g of “kumkum’’ and 300g of “eru’. Subjects’ fasting blood glucose and 90 minutes post prandial blood glucose levels were measured using a point of care glucometer.

Hence he showed that “ogbono’’ has a greater inhibitory effect on salivary alpha amylase activity in vivo than “eru’’.

So there are many other research reports on the therapeutic effect of jack fruit in managing obesity and diabetes like one in which jack fruit extract has an anti-diabetic activity being determined by inhibiting glycated haemoglobin because an increase concentration of glucose in the blood leads to its binding to haemoglobin which may result in the formation of the reactive oxygen species.

That’s why this research work is designed to explore the possible mechanism of the hypoglycemic activity of the fruit.

 1.2 STATEMENT OF PROBLEM

Obesity as well as diabetes and its associated diseases such as diabetes mellitus and cardiovascular disease is increasing in both developed and developing countries and this has led to increase death rates. Diabetes Mellitus is being one of five leading causes of deaths and debilitating disease in the world.

One hundred and fifty million people were suffering from diabetes wide reaching, which is almost five times more than the estimates one decade ago and it may double in the year 2030 (Kannan et al , 2012).

Pharmaceutical drugs have been made available to manage obesity and diabetes such acarbose, miglitol,voglibose which are expensive and may produce a lot of unwanted side effects that may even harm the liver and adrenal glands.

In addition these side effects include bloating, abdominal discomfort, diarrhoea. It is therefore of crucial importance to identify natural sources readily available, less expensive and with little or no side effects that inhibit alpha amylase.

1.3 Hypothesis

1.3.1 Alternate Hypothesis

Artocarpus heterophyllus (Jack Fruit) does not have an Inhibitory action on Amylase.

1.3.2 Null Hypothesis

Artocarpus heterophyllus (Jack fruit) has an inhibitory action on amylase.

1.4  Research Objectives  

1.4.1 General Objectives

The main aim of this study is to determine, In vivo, whether or not, the Artocarpus heterophyllus has an inhibitory action on Amylase thus defining its potential role in diabetes.

1.4.2 Specific Objectives

1. To relate the inhibitory action of Artocarpus heterophyllus (jack fruit) and Magnifera indica (mango fruit) on alpha amylase in vivo.
2. To determine the blood glucose level of some individuals before and after consumption of Jackfruit or Mango fruit with beef fried rice and slices of bread.
3. To acquire proper and adequate laboratory skills and experience.
4. To be able to assess the sugar content of both Artocarpus heterophyllus (jack fruit) and Magnifera indica (mango fruit).

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