S7: the endocrine pancreas & diabetes mellitus

Question 1

Describe the actions of insulin and glucagon

Answer 1

Insulin: increase glucose transport into adipose tissue & skeletal muscle, increase glycogenesis & decrease glycogenolysis in liver and muscle, decrease gluconeogenesis in liver, increase glycolysis in liver and adipose tissue
Glucagon: increase glycogenolysis & decrease glycogenesis in liver, increased gluconeogenesis in liver, increase ketogenesis in liver, increase lipolysis in adipose tissue

Question 2

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

Answer 2

• synthesised as pre-proinsulin on ribosomes associated with the RER
• signal peptide removed once the molecule enters the ER & here the proinsulin folds
• proinsulin is transported to the trans-Golgi apparatus & packaged into storage vesicles
• storage vesicles contain the products of proteolysis (insulin & C-peptide)
• insulin is stored in the B-cell storage granules as a crystalline zinc-insulin complex (when released it circulates as a free hormone)

Question 3

Explain the roles of insulin and glucagon in the control of metabolism

Answer 3

Insulin: effects are largely anabolic, clears absorbed nutrients from the blood following a meal
Glucagon: effects are largely catabolic, increased blood glucose concentration when its low

Question 4

Describe the condition of Diabetes Mellitus

Answer 4

A group of metabolic disorders characterised by chronic hyperglycaemia, due to insulin deficiency, insulin resistance, or both

Question 5

List the main differences between Type 1 and Type 2 Diabetes

Answer 5

Type 1 diabetes: commonest type in young, autoimmune destruction of pancreatic B-cells, rapidly fatal if not treated, must be treated with insulin
Type 2 diabetes: large number of older individuals, slow progressive loss of B-cells along with tissue resistance to insulin, may be present for a long time before diagnosis, may not initially need treatment with insulin

Question 6

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

Answer 6

Type 1: lean, young person with a recent history of viral infection who presents with a triad of symptoms – polyuria, polydipsia, weight loss
Type 2: may present with the classical triad of symptoms but more likely to present with a variety of symptoms eg. persistent infections (especially thrush of the genitalia or infections of the feet), lack of energy, visual problems

Question 7

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

Answer 7

• blood glucose is elevated due to lack of insulin
• decreased uptake of glucose into adipose tissue & skeletal muscle
• high blood glucose in urine = glycosuria
• high rates of B-oxidation of fats in the liver coupled to the low insulin/anti-insulin ratio leads to the production of huge amounts of ketone bodies
• as the ketosis develops, the H+ associated with the ketones produce a metabolic acidosis
• symptoms: prostration, hypoventilation, vomiting, dehydration

Question 8

Explain the causes and consequences of hypoglycaemia and hyperglycaemia

Answer 8

• hyperglycaemia: abnormal metabolism of glucose to products that may be harmful to cells -> uptake of glucose into cells of tissues (eg. eyes, kidney) does not require insulin & determined by extracellular glucose concentration
• hypoglycaemia: taking too much insulin, skipping/delaying a meal; symptoms include sweating, feeling tired, dizziness, turning pale & feeling shaky

Question 9

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

Answer 9

Type 1: must be managed for the rest of the patient’s life; insulin is used to treat type 1 diabetes and must be injected
Patients must be educated about their medication, dietary management & regular exercise
Frequent blood glucose measurement by finger prick using a BM stick/reader
Type 2: sometimes managed by diet, oral hypoglycaemic drugs such as sulphonylureas & regular exercise

Question 10

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

Answer 10

Persistent hyperglycaemia is associated with increased glycation
% of haemoglobin that is glycated is a good indicator of how effective blood glucose control has been (normal individuals 4-6%, poor controlled diabetics this value can increase above 10%)
As red blood cells normally spend about 3 months in the circulation the % HbA1c is related to the average blood glucose concentration over the preceding 2-3 months

Question 11

List the common long term side effects of diabetes

Answer 11

Macrovascular: increased risk of stroke & MI, poor circulation to the periphery
Microvascular: diabetic eye disease, nephropathy, neuropathy, diabetic feet

Question 12

Discuss the aetiology of metabolic syndrome and its consequences for health

Answer 12

Defined as a group of symptoms including insulin resistance, dyslipidaemia, glucose intolerance and hypertension associated with central adiposity
Metabolic syndrome is present in approximately 80% of people with type 2 diabetes & increases the risk of type 2 diabetes 5 fold and heart disease by approximately 3 fold