Comprehensive Analysis of Type 2 Diabetes: Endocrinology Assignment

This assignment delves into the intricacies of Type 2 Diabetes, beginning with the diagnostic use of the oral glucose tolerance test and its interpretation. It explores the structure and function of insulin, including its synthesis, release, and mechanism of action in regulating blood glucose levels. The assignment further examines the insulin receptor and the signaling pathways activated upon insulin binding, leading to glucose uptake and storage. Additionally, it discusses the impact of insulin on hepatic glucose metabolism, including its effects on gluconeogenesis, glycogenolysis, and glycogen synthesis. Finally, the assignment highlights the importance of dietary modifications, exercise, and the use of antidiabetic medications in managing Type 2 Diabetes, emphasizing the need for a comprehensive approach to patient care and blood sugar regulation.

Diabetes 1
ENDOCRINOLOGY ASSIGNMENT ON TYPE 2 DIABETES
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Diabetes 2
Answer to question 1
An oral glucose tolerance test is used to detect and confirm diabetes in patients suspected
to have the disease. It measures one’s body response to sugar/glucose (D'Souza et al
(2016)). It’s usually used to screen for diabetes type 2. A modified version of the same
can be used to diagnose gestational diabetes. The tolerance test is taken for a period of
two hours after ingesting glucose. In the procedure, one takes a solution that contains a
defined amount of glucose and the levels in blood are tested before, within 1 hour and
after two hours of intake of the solution. Two hours later the blood glucose levels are
tested. The expected results for a healthy person would show a normal blood glucose
level of between 3.2mmol/l to 7.8mmol/l which is the normal standard range for a
random blood sugar test. As stated by Pedersen et al (2016). The blood sugar levels
should not exceed 7.8mmol/l after the 2 hour mark for a healthy person. The fasting
blood sugar levels of a healthy person should also range between 3.9 to 6.1mmol/l when
tested. However in a pre-diabetic state the blood sugar levels range between 7.8 and
11mmol/l after the two hour mark indicating impaired glucose tolerance. The expected
results from our patient would show a blood sugar level that exceed 126mg/dl in the
fasting state and a random blood sugar levels that exceed 200mg/dl after the two hour
mark which is diagnostic for diabetes. This is because of the characteristic symptoms that
the patient had such as blurred vison and frequent urination suggestive for diabetes and
the test would be a confirmation of the disease
Answer to question 2
Insulin is a protein in nature. It is made of a dimer composed of two chains of amino
acids which are held together by bonds of disulphide. It is made of 51 amino acids. It is
made and released from beta cells of the pancreas. As echoed by Craft et al (2016), the
levels of glucose in blood are kept within range by a loop mechanism (negative feedback)
in an attempt to keep the body systems in balance. The feedback mechanism operates in a
manner such that when the blood glucose levels are high, the body looks for ways of
reducing these levels to normal. When levels of blood glucose rise, either from the
digestion of a meal or from glycogen-glucose conversion, insulin hormone is released
from a glandular group of cells within the pancreas called Langerhans where the b cells
reside. The levels of glucose in blood are detected directly by beta cells of the pancreas.
There are other causes of increase in blood sugar levels. These include the hormone
adrenaline, steroids, infections and trauma (Shungin et al (2015)). GLUT 2 transporters
form the transport channels where glucose enters the beta cells. This glucose is then
phosphorylated by kinases and is converted to pyruvate in the cytoplasm. The breakdown
of glucose involves a series of steps in a process called glycolysis into two molecules of
pyruvate. The broken down glucose in form of pyruvate enters the mitochondria and is
further broken down to water and carbon (IV) dioxide whereby ATP is formed by

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addition of phosphate molecules. The ATP from the mitochondria migrates into the
cytoplasm, where it inhibits ATP sensitive potassium channels, reducing potassium
efflux. This causes increased positive charge as potassium molecules are cations. This
causes depolarization of the beta cell and calcium enters the cell via voltage gated
calcium channels (Fajans et al (2016)). The calcium entry causes the release of secretory
granules containing insulin hence triggering the release of insulin from b cells. The liver
has several functions in the body and is involved in glucose metabolism. There are
several processes that occur in the liver as pertains glucose and these include the
formation of glucose, (gluconeogenesis), the breakdown of glycogen, (glycogenolysis)
and glycogen synthesis. Insulin being a hormone involved with glucose regulation
therefore affects the liver. It causes the liver to convert excess glucose into glycogen and
most of the body cells mainly the muscle cells and those found in fat tissue to uptake the
glucose via GLUT 4 channels leading to low levels of glucose in blood. Insulin is also
involved in protein synthesis where it encourages conversion of circulating amino acids
into protein. Examples of such amino acids are leucine and arginine. A high level of these
compounds thereby stimulates secretion of insulin as they act in a similar manner to
glucose by generation of ATP once they are metabolized. This leads to closure of
potassium sensitive pumps in the beta cells causing insulin release. (Humphrey et al
(2015). Hypoglycemia (low blood sugar levels) on the other hand reduces insulin release.
According to Sandler et al (2017), low blood glucose levels at the same time triggers the
release of four hormones which counter the activities of insulin of which the principle
hormone that counteracts this effect is glucagon. These hormones work hand in hand to
ensure that glucose levels in blood are increased to normal hence homeostasis is achieved
Answer to question 3
The receptor pf insulin is a complex made of alpha and beta subunits. It is activated by
either insulin or insulin like growth factors. As stated by Canfora et al (2015), binding of
insulin or insulin like growth factors to the alpha subunit leads to a change in
arrangements resulting into down cascade where tyrosine molecules within the beta
subunit are phosphorylated. The resulting pathway causes a series of downward cascade
involving a number of enzymes and amplification sequences that lead to glucose storage.
Insulin stimulates glucose uptake by cells including myocytes and cells found in fat
tissues (Anhê et al (2015)). It does so by inducing changes that lead to the migration of a
transporter of glucose called GLUT 4 from the intracellular storage to the plasma
membrane. Enzymes involved in the process including P 13 and kinase and AKT are
known to play an essential role in GLUT 4 movement. According to Jung et al (2014),
the activation of the receptor complex leads to a series of downward activation of a gene
encoded protein (Cbl) through phosphorylation attached to second messenger CAP. The
complex formed between the two proteins then translocate to lipid layers in the cell
membrane. The former (Cbl) after this binds crk associated with an exchange factor C3G.
The exchange factor then activates components of a larger family specifically tc10 that

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enhances movement of GLUT 4 to the cell membrane by activating an anonymous
adaptor molecule.
Answer to question 4
Insulin signaling activation also inhibits the generation and release of glucose from the
liver by inhibiting the enzymatic dependent process of its synthesis (gluconeogenesis)
and the breakdown of glycogen which is stored by the organ (glycogenolysis). As stated
by Becker et al (2015), it does so by directly controlling a number of metabolic
regulatory enzymes involved in gluconeogenesis and glycogenolysis. This involves
enzymes causing phosphorylation and dephosphorylation cascades and also is involved in
regulating the expression of genes involved in gluconeogenesis. In gene transcription,
there are promoters and inhibitors of transcription all classified in a bigger family
referred to as transcription factors. The promoters that lead to increased expression of
enzymes that promote gluconeogenesis and glycogenolysis are down regulated leading to
a decrease in blood glucose levels. Transcription factors involved in insulin signaling
pathway play a role in hepatic enzyme regulation in enzymes involving glucose. The
process of gluconeogenesis contributes to increased blood glucose hence the action of
insulin to downregulate the process leads to low sugar levels. In addition to these
processes, insulin also stimulates glucose storage in the liver. This is done by stimulating
glycogen synthesis in the liver. This process involves a number of processes that regulate
liver enzymes including glycogen synthase. In one of this insulin signaling activation
cascades, inactivation of some enzymes promote glycogen synthesis
Answer to question 5
Changes in diet and exercise in a diabetic patient helps in the maintenance of the
condition and helps the body utilize the available insulin properly to regulate blood sugar
levels. As stated by Fang et al (2015), since diabetes is a result of increased blood
glucose levels, avoiding sugary foods is crucial in regulating these levels. This includes
foods rich in sodium, high cholesterol rich foods such as dairy products whose fat content
is high and organ meats such as liver. Such food types involving fats should be avoided
in diabetic patients. This is because increased circulating keto acids may worsen diabetes
leading to coma especially in diabetic keto acidosis in type 1 diabetes patients. In as
much as avoiding certain types of food is important, the intake of certain food types is
also encouraged. These include fiber rich foods such as vegetables, fruits, nuts and
legumes and good fats such as walnuts, olives and peanut oils. These kinds of foods help
lower blood sugar levels quickly and maintain them at a normal range. Antidiabetics are
also crucial elements in controlling diabetes since they promote increased secretion of
insulin. Others down regulate hepatic activity in the process of gluconeogenesis. Exercise
is as important as diet in the maintenance of diabetes. This is because muscles become
more sensitive to insulin and absorb more glucose from blood upon exercising.

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