Session 7 ILOs - The endocrine pancreas and Diabetes mellitus

Question 1

Describe the actions of insulin and glucagon

Answer 1

Major actions of insulin:

• Stimulates glucose transport into adipose tissue and skeletal muscle
• Stimulates glycogenesis and inhibits glycogenolysis in liver and muscle
• Stimulates lipogenesis and esterification of fatty acids in liver and adipose tissue
• Stimulates lipoprotein lipase
• Stimulates amino acid uptake and proteinsynthesis in liver, muscle and adipose tissue
• Inhibits proteolysis in liver, skeletal muscle and heart muscle
• Inhibits gluconeogenesis in liver
• Inhibits lipolysis in adipose tissue
• Inhibits ketogenesis and stimulates cholesterol synthesis in liver

Major actions of glucagon:

• Stimulates glycogenolysis, gluconeogenesis and ketogenesis in liver
• Stimulates lipolysis in adipose tissue

Question 2

Describe how the ultrastructure of the β-cell relates to the synthesis and storage of insulin

Answer 2

Beta cell has:

Many mitochondria - active proteins synthesis, storage and secretion all require energy

Extensive rough ER – active synthesis of protein for export

Extensive Golgi apparatus - active formation of hormone storage vesicles

Many storage vesicles - storage of large amounts of hormone ready for secretion

Many microtubules & microfilaments - active secretory tissue (exocytosis)

Question 3

Describe the condition of Diabetes Mellitus

Answer 3

• Diabetes occurs when hyperglycaemia occurs, due to insulin deficiency, insulin resistance, or both.
• Over years this leads to damage of small and large blood vessels leading to premature death from cardiovascular diseases
• Two main types (type 1 and type 2)

Question 4

List the main differences between Type 1 and Type 2 Diabetes

Answer 4

The 2 types are clearly distinguished by their epidemiology and probable causation, but not always so easily separated clinically

• T2 has a more gradual onset, whereas T1 is more sudden
• T2 is caused by insulin resistance and/or defective insulin secretory response whereas T1 is due to an absolute insulin deficiency
• T2 is normally adult onset, often obese individuals whereas T1 is more in early adulthood
• T1 do not usually develop ketoacidosis, whereas T1 can develop ketoacidosis
• T2 is treated, at least initially with diet, drugs and exercise but T1 is treated with lifelong insulin

Question 5

Describe and explain the typical pattern of presentation of Type 1 and Type 2 Diabetes

Answer 5

T1:

• Presents in early adulthood (but can be at any age)
• Thin or normal body habitus
• Sudden disease onset
• Low or absent endogenous insulin
• Presence of ketones
• Elevated plasma glucose
• Polyuria, polydipsia and weight loss

T2:

• Presents later on in life (mostly adults)
• Generally obese
• Gradual disease onset
• Normal, decreased or increased insulin
• Can present with polyuria, polydipsia and weight loss but no urinary ketones (may be asymptomatic!)

Question 6

Explain the sequence of events leading to ketoacidosis in the uncontrolled diabetic

Answer 6

Absence of insulin has a number of effects including:

1. Increased rate of lipolysis in adipose tissue which releases large amounts of fatty acids, the substrate for ketone body formation
2. Activation of the ketogenic enzymes in the liver

Both of which lead to increased ketone body production

Question 7

Explain the causes and consequences of hypoglycaemia and hyperglycaemia

Answer 7

Hypoglycaemia (acute = emergency):

• Emergency as lack of glucose available to the vital organs
• Activation sympathetic nervous system can because trembling, palpitations, sweating, anxiety, hunger, nausea and tingling
• Decreased levels of glucose to the brain can because difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, dizziness and tiredness

Hyperglycaemia (prolonged = issue):
- If prolonged, can have microvascular and macrovascular complications

Microvascular complications
• Eye diseases, glaucoma, cataracts, retinopathy
• Nephropathy
• Neuropathy - loss of sensation, erectile dysfunction
• Diabetic feet - risk of ulceration and infection

Macrovascular complications
• Increased risk of stroke
• Increased risk of myocardial infarction
• Poor circulation to the periphery especially feet

Question 8

Describe, in broad outline, the principles of management of diabetes

Answer 8

Type 1 management:
- Lifelong insulin injections to replace missing endogenous insulin

Type 2 management:

• Diet – reduce glucose intake, reduce lipid intake
• Exercise – increase
• Drugs – lower blood glucose, lower blood lipids, insulin injections

Question 9

Explain the principle and practice of measuring glycation of haemoglobin as an index of blood glucose control in the diabetic

Answer 9

Glucose reacts with the terminal valine of haemoglobin and forms glycated haemoglobin (HbA1c - just haemoglobin with glucose attached).

Extent of glycation depends on blood glucose concentration and half- life of haemoglobin (~60days)

High blood glucose = high HbA1c
Normal blood glucose = normal HbA1c (~5%)

Can be used to monitor an individual’s glucose control over the past 3 months

Question 10

Discuss the aetiology of metabolic syndrome and its consequences for health

Answer 10

Metabolic syndrome is a cluster of the most dangerous risk factors for cardiovascular disease which include:

• Diabetes (raised plasma glucose)
• Abdominal obesity
• High cholesterol
• High BP

= together, these factors increase the likelihood of cardiovascular disease

Generally, metabolic syndrome is caused by:

• Insulin resistance and central obesity
• Genetics
• Physical inactivity
• Aging