ABSTRACT
This study was aimed at investigating the biochemical basis of dietary management of diabetes mellitus using unripe plantain in streptozotocin (STZ) induced diabetic rats. The effects of unripe plantain incorporated feeds on the regulation of glucose transport protein 1 (GLUT 1), glucose transport protein 4 (GLUT 4) and AMP-activated protein kinase (AMPK) activities as well as body weights, glycated hemoglobin, total protein, lipoprotein lipase, intestinal amylase and fasting blood glucose (FBG) levels were determined using appropriate biochemical methods. Twenty five (25) male albino wistar rats were divided into five (5) groups of five (5) rats each. Group 1 (non-diabetic), group 2 (diabetic, not treated) and group 3 (diabetic, treated with glibenclamide 5mg/kg body weight) all received standard rat feed. Group 4 (diabetic, fed unripe plantain incorporated feed 600mg/kg body weight) and group 5 (diabetic, fed unripe plantain incorporated feed 800mg/kg body weight). The experiment lasted for 28days. The fasting blood glucose levels and body weights were measured weekly, whereas all other biochemical parameters were measured at the end of the experiment. There was no significant (P>0.05) difference in the body weights of rats in groups 3 and 5 when compared to group 1 rats, whereas groups 4 and 2 rats showed significant (P<0.05) increase and decrease respectively. There was no significant (P>0.05) difference in FBG levels of groups 3, 4 and 5 rats when compared to group 1 rats, however, group 2 rats showed a significant (P<0.05) increase in FBG levels. Groups 2, 3 and 4 rats showed significant (P<0.05) increase in glycated hemoglobin levels whereas group 4 rats showed a non significant (P>0.05) increase when compared to rats in group 1. All the other groups showed significant (P<0.05) decrease in total protein when compared to group 1 rats. There was no significant (P>0.05) difference in lipoprotein lipase activity of groups 3, 4 and 5 rats while rats of group 2 showed a significant (P<0.05) decrease when compared to group 1 rats. Groups 3, 4 and 5 rats showed a significant (P<0.05) increase in GLUT 4 levels whereas group 2 rats showed a significant (P<0.05) decrease when compared to group 1 rats. Rats in group 4 and group 5 showed a non significant (P>0.05) difference whereas rats in group 2 and group 3 showed a significant decrease in GLUT 1 levels when compared to group 1 rats. There was no significant (P>0.05) difference in AMPK levels of all the groups. The results obtained show that unripe plantain possesses anti-diabetic properties and may be effective as a dietary management option for diabetics.
TABLE OF CONTENTS
Title Page i
Declaration ii
Certification iii
Dedication iv
Acknowledgments v
Table of Contents vi
List of Tables x
List of Figures xi
Abstract xii
CHAPTER
1: INTRODUCTION
1.1
Definition Of Diabetes Mellitus (DM) 1
1.2 Complications of Diabetes Mellitus 2
1.3 Effect of Diabetes Mellitus on Glucose
Transporters 2
1.4 Prevalence of Diabetes Mellitus in the
World 3
1.5 Orthodox
medicines Used in Management of Diabetes 4
1.5.1 Limitations of orthodox medicines in
management of diabetes mellitus 5
1.6 Therapeutic Plants Employed in the Management
of Diabetes Mellitus 5
1.6.1 Challenges linked to the use of medicinal
plants 7
1.7 Dietary Management of Diabetes Mellitus 8
1.7.1 Use of unripe plantain 8
1.8 Aim of
the Study 9
1.9 Objectives of the Study 10
1.9.1 Specific objectives of the study 10
1.10 Justification of the Study 11
CHAPTER
2: LITERATURE REVIEW
2.1 Definition of Diabetes Mellitus 12
2.1.1 Classification
of diabetes mellitus 13
2.1.1.1 Type 1
diabetes mellitus 13
2.1.1.2 Type 2 diabetes mellitus 14
2.1.1.3 Gestational diabetes mellitus (GDM) 15
2.2 Glucose
metabolism 16
2.2.1 Hormonal regulation of glucose metabolism 17
2.3 Glucose
Transport in Diabetes Mellitus 17
2.3.1 GLUT4 glucose transporters 18
2.3.2 GLUT1 glucose transporters 20
2.3.3 Regulation
of glucose transport 21
2.3.4 Disorders
in glucose transport in diabetes 21
2.3.5 Problems of glucose transport in diabetes
mellitus 22
2.4 Roles
of AMP-kinase in the Regulation of Glucose Transport 24
2.4.1 Roles of
AMPK in glucose metabolism 25
2.5 Roles
of Intestinal Amylase and Lipoprotein Lipase in Carbohydrate
Metabolism 26
2.5.1 Intestinal
amylase in diabetes 27
2.5.2 Lipoprotein
lipase in diabetes 27
2.6 Complications
of Diabetes 28
2.6.1 Nephropathy 29
2.6.2 Retinopathy 30
2.6.3 Neuropathy 31
2.6.4 Cardiovascular
diseases 32 2.7 Management
of Diabetes 33
2.7.1 Exercise
and diet 33
2.7.2 Drugs 34
2.8 Induction
of Diabetes 35
2.8.1
Streptozotocin 35
2.8.2 Handling of streptozotocin during induction 37
CHAPTER 3: MATERIALS AND METHODS
3.1 Materials 38
3.2 Reagents
and Chemicals 38
3.3 Collection
and Preparation of Plant 39
3.4 Formulation
of Test Feed 39
3.5 Animal
Experiments 40
3.5.1 Selection
of animals 40
3.5.2 Animal grouping 40
3.6 Induction
of Diabetes Mellitus 41
3.7 Experimental
Procedure 41
3.7.1 Assessment
of body weights of the rats 42
3.7.2 Determination
of fasting blood glucose concentration 42
3.7.3 Assessment
of feed intake 42
3.7.4 Collection
of blood 43
3.7.5 Determination
of glycated hemoglobin 43
3.7.6 Determination
of serum lipoprotein lipase activity 44
3.7.7 Determination of intestinal
amylase activty 45
3.7.8 Preparation of tissue homogenate for GLUT1,
GLUT4 and AMP-kinase
analysis 46
3.7.9 Determination of glucose transporter 4
(GLUT4) concentration 46
3.7.10 Determination of glucose transporter 1 (GLUT1)
concentration 47
3.7.11 Determination of AMP-kinase concentration 48
3.7.12 Determination
of serum total protein 48
3.8 Statistical
Analysis 49
CHAPTER 4: RESULTS AND DISCUSSION
4.1 Results 50
4.1.1 Effect
of unripe plantain incorporated feed on body weights of treated
rats 50
4.1.2 Effect
of unripe plantain incorporated feed on fasting blood glucose
levels
of treated rats 51
4.1.3 Effect
of unripe plantain incorporated feed on feed intake 52
4.1.4 Effect
of unripe plantain incorporated feed on glycated hemoglobin
levels 53
4.1.5 Effect
of unripe plantain incorporated feed on serum lipoprotein lipase
activity 54
4.1.6 Effect
of unripe plantain incorporated feed on intestinal amylase
activity 55
4.1.7 Effect
of unripe plantain incorporated feed on GLUT 4 concentration 56
4.1.8 Effect
of unripe plantain incorporated feed on GLUT 1 concentration 57
4.1.9 Effect
of unripe plantain incorporated feed on levels of AMP-kinase 58
4.1.10 Effect of
unripe plantain incorporated feed on levels of serum total
protein 59
4.1.11 Proximate
composition of test and animal feeds 60
4.2 Discussion 61
CHAPTER 5: CONCLUSION
5.1 Conclusion 66
References 67
Appendices 79
LIST
OF TABLES
PAGE
3.1 Composition of the test feeds
40
4.1 Body weights of treated rats 50
4.2 Fasting
blood glucose levels of treated rats 51
4.3 Feed intake
of treated rats 52
4.4 Glycated
hemoglobin levels of treated rats 53
4.5 Lipoprotein
lipase activity of treated rats 54
4.6 Intestinal
amylase activity of treated rats 55
4.7 GLUT 4
concentration of treated rats 56
4.8 GLUT 1
concentration of treated rats 57
4.9 AMP-Kinase
levels of treated rats 58
4.10 Serum
total protein levels of treated rats 59
4.11 Proximate composition of test and animal
feeds 60
LIST
OF FIGURES
PAGE
2.1
Structure of the Insulin-Regulated GLUT4 Glucose
Transporter
Protein 19
2.0 Structure of streptozotocin 35
1
CHAPTER 1
INTRODUCTION
1.1
DEFINITION OF DIABETES MELLITUS (DM)
Diabetes Mellitus is a global metabolic disease
characterized by hyperglycaemia and affects essential biochemical pathways in
the body resulting to complications such as; renal disorders, neuropathy,
retinopathy, ketoacidosis, and cardiovascular diseases. It is caused by
impaired regulation of the metabolism of carbohydrate and lipids where although
there is sufficient supply of glucose, the body still behaves as if it is
starved; hence glucose produced by the liver is not utilized by other tissues
(Horton et al., 2006). Its symptoms include an upsurge in the need to
urinate, raised thirst, and a surge in feelings of hunger (Cooke and Plotnick,
2008). It is classified into three types: Type 1 diabetes mellitus which can be
distinguished by damage to the insulin-producing beta-cells of the pancreatic
islets of Langerhans, which results in insulin deficiency. Type 1 diabetes is
divided into two types namely immune-mediated or idiopathic. The majority of
type 1 diabetes results from immune-mediated type, whereby a T-cell-mediated autoimmune attack results in damage
to the beta-cells and consequently insulin (Rother, 2007). It occurs at an
early age though it also affects adults. Type 2 diabetes mellitus is typified
by gradual development of resistance to insulin and beta-cell dysfunction, in
addition to decreased insulin secretion in some cases (Zimmet et al.,
2001; Gardner, 2011). The inability of body tissues to act in response insulin
appears to result from the insulin receptor. The risk for type 2 diabetes rises
with an increase in age and body weight as well as a sedentary lifestyle
(Zimmet, 1992). It is the most occurring of diabetes and usually occurs in
adults. Gestational diabetes is the third principal type and arises after
pregnant women who have not had diabetes before develop high blood-sugar levels (WHO, 2013). This type of
diabetes typically fades away once the child is born.
1.2
COMPLICATIONS OF DIABETES MELLITUS
The problems identifiable with diabetes mellitus
comprise retinopathy, nephropathy, and neuropathy. Diabetic patients suffering
from any kind diabetes for some time are susceptible to the above-mentioned
problems (Nathan, 1993).
1.3 EFFECT OF DIABETES MELLITUS ON GLUCOSE TRANSPORTERS
Glucose movement across the cell membrane is the rate limiting
step of glucose utilization and is regulated by a family of membrane proteins
known as Glucose Transporters (GLUTs) (Mueckler and Thorens, 2013).
Notwithstanding whether there is translation or
transcription, insulin and also physical activity causes acute stimulation and
recruitment of GLUT4 to the surfaces of the cells of skeletal muscle and fat
tissues (Herman and Kahn, 2006). Insulin also stimulates GLUT1 which is
expressed in the blood. Insulin appears to be the main hormone affected in diabetes
since the pancreas is involved in insulin production. Ryder et al in
2000 showed that GLUT4 translocation, in response to insulin, in the skeletal
muscle of people suffering from type 2 diabetes is usually decreased by approximately
90%. The main cellular mechanism for clearance of glucose taken from foods is
insulin-mediated glucose transport into the cells of skeletal muscle. Following
the transport step, skeletal muscle accumulates glucose in the form of glycogen
and breaks it down to produce energy when required. The main glucose transport
protein which facilitates the movement of glucose into cells is GLUT4 a member
of the sugar transport proteins family that contain 12-transmembrane domains.
The GLUT4 glucose transporter is an important facilitator of glucose clearance
out of the blood and is therefore a core controller of glucose homeostasis
(Huang and Czech, 2007). Studies have proven that although glucose transporters
move from their intracellular membrane compartment to the
surface of the cells in response to insulin, the affinity of the transporters
for glucose binding is not affected by insulin (Cushman and Wardzala, 1980;
Suzuki and Kono, 1980). There is a reduced GLUT4 protein content in
intracellular and plasma membranes of skeletal muscles of STZ-induced diabetic
rats. In STZ-treated rats, insulin caused the mobilization of GLUT4 out of the
vesicles, but the fusion of GLUT4 with the plasma membrane was diminished.
Conversely, the GLUT1 transporter protein increased in the cell membrane of the
diabetic rats (Klip et al.,1992).
1.4
PREVALENCE OF DIABETES MELLITUS IN THE WORLD
The World Health Organization estimates that,
globally, 422 million adults aged over 18 years were living with diabetes in
2014 (WHO, 2016). South-East Asia and Western Pacific Regions have the highest
occurrence of diabetes as estimated for the WHO, thus, this accounts for about
half the cases of diabetes on earth. The people with diabetes (defined in
surveys as those with a fasting blood glucose value of ≥7.0mmol/L or on
medication for diabetes/hyperglycaemia) progressively rose within the last
decades following growth in population, rise in the normal age of people in the
population, and the rise in prevalence of diabetes at each age. Worldwide,
between 1980 and 2014, people with diabetes have increased tremendously from
108 million to current numbers that are around four times higher. Forty percent
of this rise is thought to be from increase in population, twenty eight percent
from an increase in age, and thirty two percent from both increase in
population and age (WHO, 2016). The occurrence of diabetes around the universe
has increased from 4.7 percent to 8.5 percent between 1980 and 2014. This
implies that occurrence has either been on the increase or has remained
unchanged in every country (WHO, 2016). In the last decade, the incidence of
diabetes has increased in both developing and under-developed countries than in high income countries (WHO, 2016). There are
about 22 million diabetics resident in sub-Saharan Africa only. Nigeria, the
most populated country in Africa has about 4 million diabetics out of the
entire diabetics in sub-Saharan Africa. The problem with the issue of diabetes
in Nigeria is that a significant number of diabetic cases are yet to be
diagnosed and hence remain untreated (about 70%-80% of the 4 million)
(Fasanmade and Dagogo-Jack, 2015).
Nigeria
has a high occurrence of diabetes across the country. In the non-urban areas,
diabetes occurs in 0-2% of the population, but in the urban areas the numbers
higher at 5-10% (Fasanmade and Dagogo-Jack, 2015). In Nigeria, diabetes is
uncommon in children, but reports from local medical facilities posit that
there is a gradual increase in number of adolescents and children suffering
from diabetes (Fasanmade and Dagogo-Jack, 2015).
1.5
ORTHODOX MEDICINES USED IN MANAGEMENT OF DIABETES
The therapy for type-1 diabetics is administration of
exogenous insulin. Some type-2 diabetics also require exogenous insulin if they
do not respond satisfactorily to oral hypoglycaemic drugs. Drugs used for the
treatment of diabetes can be grouped into three. Drugs in group 1 boost the
amount of endogenous insulin. They include the sulphonylureas which comprise
the glinides, glibenclamide, glucagon-like peptide 1 (GLP-1) agonists, insulin
analogs, and dipeptidyl peptidase-IV (DPP-IV) inhibitors. The glibenclamide and
the glinides enhance insulin secretion by acting on the sulphonylurea receptor
found in the pancreas. Dipeptidyl peptidase-IV (DPP-IV) inhibitors and glucagon-like
peptide 1 (GLP-1) agonists effect their action on the ileal cells of the small
intestine. Drugs in group 2 enhance insulin sensitivity. They include the
thiazolidinediones, which are peroxisome proliferator-activated receptor gamma (PPARγ)agonists and
metformin, a biguanide.
Thiazolidinediones act by reducing insulin resistance in the liver, fat cells and muscle
while metformin inhibits gluconeogenesis in the liver. Drugs in group 3
comprise of α-glucosidase inhibitors like acarbose that lowers the breakdown of
carbohydrates hence their bioavailability (Chehade and Mooradian, 2000).
1.5.1
Limitations of orthodox medicines in management of
diabetes mellitus
All known treatment have shown inadequate
effectiveness, tolerance and adverse effects based on their mode of action (Moller, 2001; Rotenstein et al., 2012).
One of the adverse effects of sulphonylureas is hypoglycaemia which if not well
managed, leads to death (Erasmus et al., 1999). Thus the use of these
drugs for the treatment of diabetes has resulted in severe adverse effects.
Ongoing researches aimed at developing drugs with lower adverse effects have
yielded little success (Levey, 2002). Notwithstanding the existing treatments
available, attaining optimum glucose control continues to elude diabetics
because of retrogression in β-cell function (Wallace and Matthews, 2000). There
is also increase in complications from diabetes and hyperglycaemic emergencies
(Gill et al., 2009;
Ogbera et al., 2007;
Ogbera et al., 2009). In the light of these, the volume of drugs
administered has risen to tremendously (Enwere et al., 2006). The high
cost of these drugs and the need to take them continuously, even with the
associated adverse effects has been identified as the reason why diabetics do
not adhere to treatment schedule. Besides the above mentioned, there is the
problem of inadequate accessibility to these orthodox medicine to treat
diabetes in middle and low income countries.
1.6 THERAPEUTIC PLANTS EMPLOYED IN THE
MANAGEMENT OF DIABETES MELLITUS
Following the side effects and high cost of diabetic
drugs, patients usually turn to other forms of therapy like the medicinal
plants (Yusuf et al., 2008). Many plant remedies known in folkloric medicine are being employed in
treatment of hyperglycemia in diabetics. Some of these plant preparations have
been substantiated by research studies and found to exert biological actions
against the complications of diabetes and diabetes itself (Ezuruike and Prieto,
2014). Several mechanisms have been adduced for the hypoglycaemic action of
medicinal plants. These include reabsorption of glucose by the kidneys,
improved insulin secretion by beta-cells, improved glucose uptake by tissues
following improved insulin sensitivity, rejuvenation/repair of beta cells,
accelaration of glycogenesis and hepatic glycolysis, rise in size and quantity
of cells of the islets of Langerhans, protective effects on the destruction of
the beta-cells and/or prevention of oxidative stress that is possibly involved
in damage to pancreatic beta-calls (Ismail-Beigi, 1993). In Nigeria, it is
common to use plants (herbs or food plants) in isolation or along with
medicines in diabetes management. The diets/medicinal plants frequently
employed in treatment of diabetes in Nigeria include: sweet potato (Ipomoea
batatas), acha (Digitaria exillis), okro (Abelmoschus
esculentus), breadfruit (Treculia africana), bitterleaf (Vernonia
amygdalina), beans (Phaseolus vulgaris), Aloe vera, garlic (Allium
sativum), Momordica charantia,alligator pepper (Aframomum melegueta),
(Eleazu and Okafor, 2012; Ezuruike and Prieto, 2014; Nwaoguikpe, 2010).
The hypoglycaemic effect of these plants stems from the presence of certain
biochemicals present in them. Lupenyl cinnamate, lupenyl - and cetate-amyrin β cinnamates and isolated α
from the combined root and stems of locally obtained samples of Gongronema
latifolium, otherwise known-masro’‘utazi’inIgbor
and‘maduYoruba is commonly used as a food vegetable and is widely recognized
for its traditional use in diabetes management) have recently been identified as
the bioactive compounds, possessing both anti-hyperglycaemic effects in
glucose-fasted rats in addition to its ability to stimulate insulin in INS-1
cells (Adebajo et al., 2013). Kolaviron is a biflavonoid isolated from
extracts of the edible nuts of Garcinia kola Heckel (bitter kola), which is of significant importance in many
regions of West Africa. It reduced blood glucose concentration in non-diabetic
and alloxan-induced diabetic mice at a dose of 100 mg/kg, besides inhibiting
rat lens aldose reductase (RLAR) activity (Iwu et al., 1990).
Some methoxy phenyl derivatives present in the rhizomes of Zingiber
officinale Roscoe have been identified as aldose reductase
inhibitors. They repress accumulation of sorbitol in human red blood cells and
also reduce accumulation of lens galactitol in 30% of galactose-fed rats (Kato et
al., 2006). Fractionating the bark of Cassia fistula L. showed that
the plant contains catechin as its active compound. Catechin reduced blood
glucose levels in STZ-induced diabetic rats by acting directly on enzymes
involved in glucose breakdown and also on GLUT4 expression (Daisy et al., 2010).
Quercetin and epicatechin are both able to inhibit the development of advanced
glycated end products (AGEs) as well as other complications of diabetes that
result from oxidative stress conditions like erectile dysfunction, artherosclerosis,
neuropathy, nephropathy and retinopathy (Rahimi et al., 2005). Bush
mango (Irvingia gabonensis), mahogany (Khaya senegalensis), mango
(Mangifera indica), and scent leaf (Ocimum gratissimum) all
contribute to an all round treatment of diabetes as well as the prevention of
diabetic complications because they contain quercetin, epicatechin and other
effective flavonoids (Ezuruike and Prieto, 2014).
1.6.1
Challenges linked to the use of medicinal plants
The major challenges of traditional medicine are overall
quality, safety and effectiveness of the medicines. Preservation and dosage
measurements of the medicines are serious problems too. However, despite their
challenges, herbal medicines afford research in science great prospect for
development (Erah, 2002).
1.7
DIETARY MANAGEMENT OF DIABETES MELLITUS
Before the 1920s when insulin was introduced, the sole
treatment for diabetes was dietary (Chandalia et al., 2000). After the
coming of insulin and other drugs there exist quite a number of limitations in
their use even though they have been useful for managing the disease. These
limitations include their side effects and high cost as well as lack of
accessibility to low income countries. Another important limitation is the need
to combine two or more of these drugs for better effects. These reasons have
made it preferable to embrace and adopt alternatives which include dietary
management. Chandalia et al., 2000 showed that increasing consumption of
soluble fiber is one effective dietary treatment. Its benefits in terms of
serum cholesterol concentrations and colonic function are well established
(Bruce et al., 2000). Another concept is the incorporation of foods with
low glycaemic index in the diet. Miller, 1994 determined that diets that
incorporate low glycaemic index foods reduce hyperglycemia in type 2 diabetes.
In addition, the production of free fatty acids is usually lower after a meal
that has a low glycaemic index. This is good for diabetics since insulin
resistance is promoted by fatty acids. Lower insulin resistance after a meal
translates into lower blood glucose concentrations. Results from various
studies indicate that dietary manipulation produces dividends in diabetics.
Combining a high fiber diet in addition to other foods with low glycaemic index
successfully lowers blood glucose levels synergistically (Chandalia et al.,
2000; Bruce et al., 2000). It is necessary to note that although
carbohydrates that have low glycaemic index appear to be desirable, elimination
of carbohydrates is not beneficial.
1.7.1
Use of unripe plantain
Plantain (Musa paradisiaca) is a major food
crop in the tropical and sub-tropical regions of Africa and the staple supply
of energy for many people dwelling in these regions (Adepoju et al.,
2012). In Nigeria, roughly 2.4 million metric tonnes of plantain is produced from a state in the southern region
(Folayan and Bifarin, 2011). In Nigeria, plantain is widely used in an array of
ways and hence it is placed among the staple foods in this country. Musa
paradisiaca (plantain) is a member of the Musaceae family, the perennial
tropical giant plant. Plantain fruits can be consumed in any form (Nwokocha and
William, 2009). It has been shown that unripe plantain contains 83.40%
carbohydrate, 8.10% protein, 1.10% fat, 1.50% fiber, 0.46% moisture, and 1.10%
ash. It is also abundant in vitamin K, provitamin A, and vitamin C. Saponins, alkaloids,
tannins and flavonoids are also present in substantial amounts (Eleazu et
al., 2011). Other studies have recorded the presence of vitamin C, vitamin A, vitamin B
complex, vitamin E, as well as high potassium in addition to low sodium in
plantains (Marriott and Robinson, 1981). Plantain is also known to be rich in
iron, fibre, vitamins, minerals, and serotonin (Jimmy and Okon, 2012). Unripe
plantain is employed in traditional medical practice for the management of
diabetes, treatment of anemia and treatment of ulcers (Ekpo et al.,
2011). In Nigeria, meals made using unripe plantain have been adduced to lower
postprandial glucose levels in diabetics (Willet et al., 2002). The
ability of unripe plantain to reduce the prevalence of diabetes has been
reported in experimental animals. Previous studies show that unripe plantain
can ameliorate glomerular complications, liver hypertrophy and kidney
hypertrophy in Streptozotocin-induced diabetic rats (Eleazu et al.,
2010; Eleazu and Okafor, 2015). Its anti-hyperglycaemic effect has also been
established (Iroaganachi et al., 2015).
1.8
AIM OF THE STUDY
The use of unripe plantain as a source of dietary
management of diabetes has been established (Eleazu and Okafor, 2015;
Iroaganachi et al., 2015). However, the mechanism by which unripe plantain
exerts this function is not clear. Thus the possible effect of formulated
unripe plantain diet in regulation of GLUT4 and GLUT1 (principal transporters
of glucose) forms the basis of this work.
Based on above, the purpose of this study is to investigate
the possible effect of formulated unripe plantain diet in the regulation of
GLUT4 and GLUT1 transporters.
1.9
OBJECTIVES OF THE STUDY
The overall objective of this work is to determine the
possible effect of a formulated unripe plantain diet on regulation of GLUT4 and
GLUT1 and on other biochemical parameters such as AMPK, glycated haemoglobin
levels, intestinal amylase, and lipoprotein lipase activity.
1.9.1
Specific objectives of the study
·
To investigate the possible effect of
formulated meal of unripe plantain on the concentrations of GLUT4 and GLUT1
glucose transporters because a low concentration of the transporters indicates
a low level or insensitivity of insulin.
·
To
determine the AMPK activity as their effect is diminished in diabetic rats.
·
To investigate serum amylase and lipase
activities as it indicates the existence of acute pancreatitis in the diabetic
rats.
·
To ascertain the effect of the meal on
body weights and feed intake because alteration in cellular metabolism manifest
in body and organ dysfunction and weight alteration.
·
To determine the level of glycation of
haemoglobin because levels of HbA1c is a very good indicator of diabetic state
in rats.
·
To ascertain the effect of the meal on
blood glucose levels because blood glucose levels are indicators of diabetes in
the STZ-treated rats.
·
To determine the proximate analysis of the
test feeds since components of food determine their impact on hyperglycemia
1.10
JUSTIFICATION OF THE STUDY
Following the alarming rate at which the incidence of
diabetes is snowballing and in the light of the potentials that unripe plantain
has in its management, there is need for studies that could help in our
understanding of the biochemical basis for such dietary management of the
disease. No doubt many studies have corroborated that unripe plantain is
effective in diabetes management, this study however seeks to delve into the
effect that unripe plantain has on regulation of GLUT4 and GLUT1 glucose
transport proteins in the skeletal muscle and blood respectively in a bid to
tackle hyperglycemia.
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