Pancreatic Endocrinology - Essay

1.

A 24-year-old female is investigated for recurrent loss of consciousness, palpitation,

and sweating. The following investigations are done and a diagnosis of an insulin-
secreting tumor in the pancreas is made

Fasting blood glucose – 45mg/dl (70-110mg/dl)

C peptide level – 15ng/ml (0.6-3.2ng/dl)

Magnetic Resonance Imaging (MRI) of the pancreas shows a tumor in the tail of the
pancreas which was surgically removed.

1.3 Briefly explain the reason for the C-peptide level observed in this patient. (20
marks)

1.4 Briefly explain the reasons for her palpitations and sweating. (20 marks)

• The patient has an insulin secreting tumour or an insulinoma.

• Insulin reduces the blood glucose level by increasing the peripheral utilization
and reducing hepatic glucose output.
• Since insulin is in excess the patient becomes hypoglycaemic.
• Carbohydrate reserves of neural tissues are limited.
• Therefore normal functioning of the brain depends on continuous glucose
supply.
• Palpitations and sweating due to the autonomic discharge.

1.5 List four hormones that act to overcome her symptoms. (10 marks)

1.6 Briefly explain the mode of action of insulin. (20 marks)

2.
A 55-year-old man presents with severe thirst and polyuria. He has lost weight over
the past five months.

The following are his investigation findings.

Urine glucose +++

Blood glucose 400mg/Dl

4.1 Give the physiological basis for his

4.1.1 Glycosuria (20marks)

• Glycosuria is passing glucose in urine.

• It is due to hyperglycaemia exceeding renal threshold.
• Diabetes mellitus is associated with high blood glucose levels.
• Lack of insulin in diabetes mellitus gives rise to wide spread biochemical
abnormalities due to reduce entry of glucose into peripheral tissues and
increased hepatic glucose output.
• The peripheral utilization of glucose is reduced as the insulin dependent
glucoseuptake by GLUT4 to muscles and adipose is impaired due to lack of
insulin.
• Intracellular glucose deficit causes a lack of the major source of energy.
• As a result (1) glycogenolysis and (2) gluconeogenesis get activated and
increase therelease of hepatic glucose.
• Both the factors contribute towards extracellular hyperglycaemia.
• When the blood glucose levels exceed the renal threshold (180mg/dl of
venousblood) and transport maximum, glucose appears in urine causing
glycosuria.
• Transport maximum is the maximal rate at which renal active transport systems
cantransport glucose 100% reabsorbed.
 • Renal threshold is the concentration of a substance at which it first appears in
urine.

4.1.2 Thirst (15 marks)

• When the blood glucose levels exceed the renal threshold (180mg/dl of venous
blood) and transport maximum, glucose appears in urine causing glycosuria.
• Glucose is osmotically active and drags water into the renal tubules. This is
called osmotic diuresis.
• Osmotic diuresis causes total body water to reduce.
• Due to osmotic diuresis lot of water is lost from the body leading to
dehydration.
• When water is lost ECF volume reduces.
• Plasma volume reduces.
• Osmolality increases.
• Increased osmolality is sensed by osmoreceptors in the hypothalamus.
• Then the thirst center is stimulated and ADH is released.
• This causes polydipsia.

4.1.3 Polyuria (15 marks)

• Polyuria means the excretion of excess water in urine.

• In DM glucose concentration in blood is high.
• When it exceeds the transport maximum and the renal threshold, glucose
appears in urine.
• Glucose is osmotically active.
 • It creates an osmotic gradient for water and drags water into the renal tubules.
• Ultimately a lot of water is excreted in urine.
• This process is called osmotic diuresis.

3.

5.2 Outline the mechanism by which insulin mediates the uptake of glucose in skeletal

muscle. (20 marks)

5.3 A 23-year-old man presents with severe polyuria and polydipsia. On examination,

He is thin and wasted. On inquiry he states that he has lost weight over the past one

year. His investigation results are as follows:

Urine glucose +++

Ketone bodies +

Blood pH 7.31

Blood glucose 380mg/dL

Briefly explain the physiological basis for the following.

5.3.1 Glycosuria (25 marks)

5.3.2 Blood pH level (15 marks)

5.3.3 Weight loss (10 marks)

• 1g of glucose= 4.1kcal.
• When glucose is lost in urine, energy is also lost.
• Inside cells, glucose is lacking due to reduced peripheral utilization.
• Therefore the muscle proteins are catabolized.
• Amino acids enter liver and used as raw materials for GNG.
 • As muscles are wasted, weight is lost.
• In adipose tissues fat is broken down and FFAs are used for energy generation.
• Again the weight is lost.
• Due to glycosuria, glucose is present in urine.
• Glucose is osmotically active and drags water into the renal tubules. This is
called osmotic diuresis.
• Osmotic diuresis causes total body water to reduce.
• It also contributes to weight loss.

4.

5.2 A 60-year-old female has been on oral corticosteroids for her rheumatoid arthritis
for the past 10 years. She has now developed diabetes mellitus and hypertension. Her
General Practitioner attributes this to the side effects of the drug.

5.2.2 State the action of cortisol on carbohydrate metabolism and give reasons for
diabetes mellitus in this patient. (25 marks)

5.

5.3 A 60 years old unconscious female was seen in the emergency unit. Her
respiratory rate was 40/minute. The random blood glucose level was 430mg/dl.

Arterial blood gas findings

pH - 7.3

HCO3- - 14mmol/L

PaO2 - 105mmHg

PaCO2 - 35mmHg

5.3.1 State the likely diagnosis. (10 marks)

5.3.2 Explain the reasons for her random blood glucose level. (25 marks)
5.3.3 List three other hormones elevated in her. (15 marks)

5.4 Briefly describe the structure of the insulin receptor and its role in the mechanism
of action of insulin. (20 marks)

6.

5.3 A man with recurrent syncopal episodes had following findings.

Random glucose level 35 mg/dL

Fasting Insulin level High

Fasting C-peptide level Low

a) State the likely cause for his syncopal episodes. (05 marks)

b) State the likely cause for his random blood glucose level. (05 marks)

c) Outline the mechanism of insulin secretion by beta cells in a healthy individual. (30
marks)

d) List four (4) other hormones likely to be secreted when random blood glucose is 35
mg/dL. (10 marks)

e) Explain the mechanism by which insulin mediates the uptake of glucose in insulin
sensitive. (20 marks)

7.
8.

9.
5. A 25-year-old female had a routine 2 hours oral glucose tolerance test at the 24th
week of gestation. The following were the results.
• Fasting glucose - 105 mg/dl (normal <92 mg /dl)
• One hour after - 200 mg/dl (normal <180 mg /dl)
• Two hours after- 240 mg/dl (normal<153 mg/dl)
5.1 What is the most likely diagnosis?
5.2 Explain the metabolic effect you would expect in the liver, adipose tissue, and
muscle due to her current condition?
After the delivery, FBG was 85 mg/dl.
5.3 State the basis for the normalization of her blood glucose level?
 Pancreatic Endocrinology - MCQ
1. Insulin.

A. It is a glycoprotein.

B. It is secreted in equimolar amount with peptide.

C. Secreted as pre hormone.

D. Needs ca2+ for its secretion.

E. Secretion is increased with hyperpolarization of β cell membrane.

2. Insulin excess results in (immediate response)

A. Catabolism of proteins

B. Increased appetite

C. Hypoglycemic episodes

D. Reduction of Serum K+ increased ketogenesis

E. Increased ketogenesis

3. Which of the following statements regarding insulin are true

A. It is synthesized by the B cells in the pancreas

B. Insulin and C peptide are present in equal amounts

C. It increases protein catabolism

D. It increases plasma protein level

E. Its secretion is inhibited by alpha adrenergic receptor stimulation

4. Insulin secreted by beta cells,

A. Stimulated by reduced plasma glucose

B. Depends on ATP generation

C. Triggered by closure of potassium channels

D. Limited by the rate of glucokinase activity

E. Increase by sympathetic stimulation

5. Regarding insulin,

A. Secreted as a preprohormone by RER

B. Pancreatic beta cells secrete equal amounts of insulin and C proteins

C. Stimulate entry of glucose to skeletal muscle cells by facilitated transport

D. Sgl2 transporters are seen in DCT

E. Glycogen inhibits insulin secretion

6. Regarding insulin,

A. Its secretion is associated with equal amounts of C peptide.

B. Facilitates GLUT 4 translocation to the cell membrane of adipose tissue.

C. It stimulates protein degradation.

D. It increases fatty acid synthesis in adipose tissue.

E. It decreases hepatic glycolysis.

7. What are the effects of insulin resistance ?

A. Decreased glucose utilisation.

B. Inhibition of the RAS / MAPK pathway.

C. Elevated hepatic glycogen.

D. Reduction of endothelial Nitric oxide synthase (eNOS).

E. Activation of glycogenic pathway.

8. What are the true statements regarding insulin?

A. Peptide C is secreted in equimolar concentrations

B. Causes GLUT 4 translocation on skeletal muscles

C. Decrease lipoprotein lipase activity in adipose tissues

D. Increase protein degradation

E. Decrease glycogenolysis in liver

9. Which of the following effects take place in IP3 kinase pathway

A. Activation of serine kinase activity on receptor

B. Cross phosphorylation of the receptor

C. Activation of MAP kinase

D. Phosphorylation of IRS 1

E. Conversations of PIP2 to PIP3 in cell membrane

10. Regarding the hormone Insulin,

A. Synthesized as a preprohormone in Rough Endoplasmic reticulum

B. Secretion is stimulated by intestinal peptides

C. Stimulates protein degradation

D. Increase fatty acid synthesis in adipose tissue.

E. Decrease glycolysis in liver.

11.A 90-year-old women with a history of diabetes mellitus for 3 years presented to
the diabetic clinic for follow up treatment. Upon examination following were her
Laboratory results:

Fasting plasma glucose 205mg/dl

Hba1c 9.4%

Lipid profile:

Total cholesterol 225 mg/dl

HDLC 32 mg/dl

LDLC 187 mg/dl

Triglycerides 280 mg/dl

(All the reference values were given except Fasting plasma glucose level)

Which of the following reasons are true regarding dyslipidemia of the above patient,

A. Insulin resistance

B. Increased VLDL secretion by the liver.

C. Increased lipolysis in adipose tissue.

D. Decreased lipoprotein lipase activity.

E. Decreased catabolism of liver.

12. Regarding Insulin resistance,

A. Increased VLDL synthesis in Liver.

B. Increased actions of enzymes of gluconeogenesis.

C. Increased lipolysis in adipose tissue.

D. Increased glucose uptake through GLUT 2 transporters in the liver.

E. Increased Amino acid uptake by skeletal muscles.

Pancreatic Endocrinology - SBA

1. Which of the following metabolic activity will increase in a person with
uncontrolled DM?

A. Glucose entry into skeletal muscle.

B. Protein synthesis.

C. KB formation.

D. Glycogen synthesis.

E. K+ entry into cell entry.

2. A 35-year-old woman presented to the clinic with confusion and her blood glucose
level revealed to be 50 mg/dL. What is the most probable finding in her?

A. Hypotension

B. Dehydration

C. Sweating

D. Constricted pupils

E. Polyuria
3. C-peptides use to estimate B cell function in human. What is the rationale for
measuring C peptide rather than Insulin?

A. C-peptide is a part of the insulin molecule in the circulation

B. C-peptide measurement reflect insulin secretion also in subjects treated with insulin

C. Can measured small amount of plasma than insulin

D. Sensitivity and specificity higher than insulin

E. Is degraded less easily than insulin

4. A 40 year old man with recurrent syncope,

Blood glucose = low during each episodes

C-peptide = low

Best explanation;

A. Prolonged fasting

B. Insulin secreting tumor in pancreas

C. Insulin overdose

D. Dumping syndrome due to gastrectomy

E. Reduced glucagon secretion

5. A person presented with

Peptide C - 4.2

Glycosylated HbA1c - 7.3

A. Down regulation of insulin receptors.

B. Insulin deficiency

C. Insulin resistance

D. Insulin secreting tumor

E. Over stimulation of receptor tyrosine kinase

6. A 52 year old female presented with recurrent hypoglycaemic attacks. Investigation

results are as follows.

• Fasting Blood Glucose levels : 45 mg/dL

• Insulin : 55 mIU/L (<25 mIU/L)

• C peptide level : 3 nmol/mL (0.5 - 2 nmol/mL)

• Urine Sulphonylurea : Negative

What would be the most likely diagnosis?

A. Prolonged fasting

B. Excess hypoglycaemic drug usage

C. Exogenous insulin administration

D. Hepatoma causing IGF 2 secretion

E. Insulinoma

7. A 40yr old man had a recurrent hypoglycaemic attack. He was a diabetic patient.

· Blood glucose level 45mg/dL

· Serum insulin 55μU/L (5- 25 uU/L )

· C peptide 0.01uU/L (0.2-0.34 uU/L)

What is the diagnosis?

A. Hypothalamic damage

B. Oral hypoglycaemic drugs

C. Exogenous insulin administration

D. Hepatoma causing IGF 2 factor

E. Insulinoma

8.A 12-year-old girl is admitted with recent onset of loss of weight and polydipsia for
2 weeks. Her random blood glucose level is 430mg/dl, Which of this test indicates
pancreatic beta cell reserve?

A. Insulin autoantibodies

B. Pancreatic cell biopsy

C. Plasma glucose level

D. Serum C peptide level

E. Serum glucagon level

9.Type 1 Diabetes mellitus characteristics is?

A. Insulin resistance

B. Absolute insulin deficiency

C. Relative insulin deficiency

D. Decreased beta cell mass

E. Decreased beta cell function

10.A 25-year-old diabetic male was bought to emergency in semiconscious state.
Blood investigations revealed below results.

Random glucose level - 50mg/dL

Plasma C Protein - undetectable

What is likely cause for his presentation,

A. Diabetic ketoacidosis

B. insulin deficiency

C. Insulin overdose

D. Insulin resistance

E. Prolonged starvation

11.A 40 year old female was experiencing dizziness and nausea. her serum showed
glucose 45mg/dl and reduced c peptide, increased insulin levels. Her finding showed

A. reduced gluconeogenesis

B. exogenous insulin secretion

C. Exogenous insulin administration

D. IGF 2 secreting tumor

E. Insulin secreting tumor

 Pancreatic Endocrinology – OSPE