EFFECT OF CAFFEINE ON BLOOD GLUCOSE AND LIPID PROFILE IN ALLOXAN-INDUCED DIABETIC WISTAR RATS

Thesis Overview

<p> <b>1.0 INTRODUCTION&nbsp;</b></p><p><b>1.1&nbsp;&nbsp;DIABETES MELLITUS</b><b></b></p><p>Excessive urine excretion is one of the major symptoms of diabetes. The most common form of diabetes is diabetes mellitus, a metabolic disorder in which there is an inability to oxidize carbohydrate due to disturbances in insulin function. Diabetes mellitus is characterized by elevated glucose in the plasma and episodic ketoacidosis. Additional symptoms of diabetes mellitus include polydipsia, glucosuria, polyuria, lipemia and hunger (King et al., 1998; WCPD, 2012). Diabetes mellitus is a heterogeneous clinical disorder with numerous causes. Two main classifications of diabetes mellitus exist, idiopathic and secondary. Idiopathic diabetes is divided into Type 1 diabetes (IDDM) and Type 2 diabetes (NIDDM) (WHO, 2003). Type 2 diabetes is associated with a cluster of interrelated plasma lipid and lipoprotein abnormalities, including reduced HDL cholesterol, a predominance of small dense LDL particles, and elevated triglycerides. These abnormalities occur in many patients despite normal LDL cholesterol levels. These changes are also a feature of the insulin resistance syndrome (also known as the metabolic syndrome), which underlies many cases of type 2 diabetes. In fact, pre-diabetic individuals often exhibit an atherogenic pattern of risk factors that includes higher levels of total cholesterol, LDL cholesterol, and triglycerides and lower levels of HDL cholesterol than individuals who do not develop diabetes (Krauss, 2004). World Health Organization (WHO) estimated that approximately 120-140 million people were globally affected by diabetes mellitus in 1999 (WHO, 1990). In 2000, this figure increased to more than 177 million (Kalda et al., 2008) and is projected to 2 increase to 221 million by 2010 and to double by the year 2025 (King et al., 1998 and Emerson et al., 2009).&nbsp;</p><p>1.2 <b>ALLOXAN</b></p><p>(2, 4, 5-6-pyrimidinetetrone) Alloxan and streptozotocin are widely used to induce experimental diabetes in animals. The mechanism of their action in β cells of the pancreas has been intensively investigated and now is quite well understood. The cytotoxic action of both of these diabetogenic agents is mediated by reactive oxygen species. However, the source of their generation is different. Alloxan and the product of its reduction, dialuric acid, establish a redox cycle with the formation of superoxide radicals. These radicals undergo dismutation to hydrogen peroxide. Thereafter highly reactive hydroxyl radicals are formed by the Fenton reaction. The action of reactive oxygen species with a simultaneous massive increase in cytosolic calcium concentration causes rapid destruction of β cells (Szkudelski, 2001).&nbsp;</p><p>1.3 <b>CAFFEINE</b></p><p>Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug and an acetyl cholinesterase inhibitor (Cardoso-Lopes et al., 2009). It is found in varying quantities in the seeds, leaves, and fruits of some plants, where it acts as natural pesticides that paralysis and kills certain insects feeding on the plants. It is most commonly consumed by humans in infusions extracted from the seeds of the coffee plant and the leaves of the tea bush, as well as from the various foods and drinks containing products derived from the Kola nut. In humans, caffeine acts as a central nervous system stimulant, temporarily warding off drowsiness and restoring alertness. It is the world most widely consumed psychoactive drug, but unlike many other 3 psychoactive substances, it is both legal and unregulated in nearly all parts of the world. Beverages containing caffeine such as coffee, tea, soft drinks, and energy drinks, enjoy great popularity; and about 90% of adults consume caffeine daily (Lovett, 2005).&nbsp;</p><p>1.3.1 <b>CAFFEINE AND DIABETES</b></p><p>Coffee is the most widely consumed beverage in the world and heavy coffee consumption has been associated with a lower risk of diabetes, but little is known about the mechanisms responsible for this association. Caffeine is one of the active biological components in coffee and is the principal source of the suggested benefits of coffee consumption. The effect of caffeine on glucose tolerance is still controversial, however (Urzua et al., 2012). Caffeine had been reported to somewhat reduce the risk of type 2 diabetes (Van Dam, 2008). A growing body of research suggests that caffeine disrupts glucose metabolism and may contribute not only to the development of but also the control of type 2 diabetes, a major public health problem (Lane, 2011). It has also been reported that caffeine may increase the effectiveness of some medications (Gilmore et al., 2011).&nbsp;</p><p>1.4 <b>METFORMIN</b></p><p>Metformin is a hypoglycemic biguanide diabetic medication which acts by reducing the release of glucose from the liver and increasing glucose uptake by the muscles (Klip and Leiter, 1990). Metformin has been used for over 40 years as an effective glucose lowering agent in type 2 (non-insulin dependent) diabetes mellitus. It is an oral biguanide that ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production (Muharnniad et al., 2000).&nbsp;</p><p>1.5 <b>STATEMENT OF THE RESEARCH PROBLEM</b></p><p>There is growing concern that diabetes will assume epidemic proportions affecting the developing world in Asia and Africa more than the developed world (Amos et al., 1997; Rheeder, 2006). Diabetes mellitus is a risk factor for cardiovascular disease, stroke, amputation and blindness (Gong et al., 2009; Duze et al., 2012). Findings have indicated that caffeine intake influences glucose metabolism (Lane et al., 2004) while caffeine and coffee have been shown to have exaggerating effects on postprandial hyperglycemia, a condition that can worsen type 2 diabetes mellitus (Lane et al., 2007).&nbsp;</p><p>1.6&nbsp;<b>JUSTIFICATION FOR THE STUDY&nbsp;</b></p><p>While it is expedient that we are certain about the effects of caffeine on diabetes mellitus since it is popularly consumed in the Nigerian society in various forms, there is the need to also clear the seeming controversy over the effect of caffeine the active ingredient in kolanut, coffee, tea, chocolate and cola drinks on diabetes mellitus. The reports of certain previous studies on caffeine were contradictory. While some indicated that caffeine exerts a protective effect against the onset of diabetes mellitus (Shearer et al., 2003; Van Dam et al., 2006; Shearer et al., 2007), recent studies have shown that it actually increases insulin resistance, a factor, in the development of type 2 diabetes (Van Dam, 2006; Lane, 2011). These recent studies conflict with past studies about coffee which have consistently found that coffee drinkers have a lower risk of developing type 2 diabetes mellitus and that the consumption of coffee may ameliorate the effects of the disease.&nbsp;</p><p>1.7 <b>AIM AND OBJECTIVES&nbsp;</b></p><p>The aim of this study is to determine the effects of caffeine on blood glucose and lipid profile in alloxan-induced diabetic Wistar rats. The specific objectives of this study are as follow:&nbsp;</p><p>i. To study the acute and sub-chronic effects of caffeine on blood glucose level in alloxan- induced diabetic rats.&nbsp;</p><p>ii. To investigate the effect of caffeine on lipid profile in alloxan-induced diabetic rats.&nbsp;</p><p>iii. To investigate the effect of caffeine on the body weight of alloxaninduced diabetic Wistar rats.&nbsp;</p><p>1.8 <b>HYPOTHESIS</b></p><p>&nbsp;Caffeine has no significant effects on blood glucose level and lipid profile in alloxaninduced diabetic Wistar rats.&nbsp;</p>