Diabetes mellitus and glucose homeostasis

Question 1

What is the definition of diabetes mellitus? [3]

Answer 1

a condition characterised by hyperglycaemia / due to lack of insulin (insulin deficiency) / or reduced effectiveness of endogenous insulin (insulin resistance)

Question 2

What are some complications of hyperglycaemia? [7]

Answer 2

microvascular -

1. retinopathy
2. nephropathy
3. neuropathy

macrovascular -

1. stroke
2. MI/heart disease
3. renovascular disease
4. limb ischaemia

Question 3

What should normal blood glucose levels be? [1]

Answer 3

between 3.5 - 8.0mmol/L

Question 4

How much glucose is produced and utilised each day? [1]

Answer 4

~200g of glucose

more than 90% derived from liver glycogen and hepatic gluconeogenesis, remainder from renal gluconeogenesis

Question 5

What organ is the major consumer of glucose? [3]

Answer 5

1. the brain is dependent on glucose to function
2. glucose uptake is obligatory so not dependent on insulin
3. the brain cannot use free fatty acids (FFA) for Kreb’s cycle as FFA cannot cross the blood brain barrier

Question 6

How is glucose used in muscles? [2]

Answer 6

1. glucose is stored as glycogen

2. or metabolised to lactate or CO2 and H2O

Question 7

How is glucose used in adipose tissue? [2]

Answer 7

1. glucose is used as a substrate for triglyceride synthesis

2. lipolysis of triglyceride releases FFA and glycerol, with glycerol then being used for hepatic gluconeogenesis

Question 8

What cells produce insulin and how is it produced? [4]

Answer 8

1. insulin is produced by pancreatic beta cells
2. proinsulin is the precursor of insulin and contains alpha and beta chains of insulin joined together by C peptide
3. when insulin is produced, proinsulin is cleaved from its C peptide to make insulin which is then packaged into insulin secretory granules
4. synthetic insulin does not have C peptide

Question 9

What are the actions of insulin? [6]

Answer 9

1. increase glucose uptake into muscle and fat cells
2. increase glycogenesis
3. decrease glycogenolysis
4. decrease gluconeogenesis
5. decrease lipolysis
   6, decrease breakdown of muscle (ketogenesis)

Question 10

What is biphasic insulin release? [3]

Answer 10

1. pancreatic beta cells can sense rising glucose levels and aim to metabolise it by releasing insulin
2. first phase response is the rapid release of stored insulin
3. if the glucose levels remain high, the second phase is initiated, however it takes longer as more insulin must be synthesised

Question 11

What cells produce glucagon? [1]

Answer 11

pancreatic alpha cells

Question 12

What is the action of glucagon? [6]

Answer 12

1. increase glycogenolysis
2. increase gluconeogenesis
3. increase lipolysis
4. increase breakdown of muscle (ketogenesis)
5. decrease peripheral glucose uptake
6. decrease glycogenesis

Question 13

Where are GLUT-2 transporters found and what is their action? [2]

Answer 13

1. GLUT-2 transporters are found in pancreatic beta cells
2. they transport glucose into the beta cell and allow beta cells to detect high blood glucose levels and release insulin in response

Question 14

How is insulin released? [5]

Answer 14

1. high glucose concentrations so glucose enters the beta cell via GLUT-2 transporter
2. glucose metabolised and ADP –> ATP
3. closing of K+ channels and depolarisation of membrane
4. opening of Ca2+ channels and Ca2+ influx which bind to insulin secretory granules
5. granules fuse with cell surface membrane and release insulin from vesicles by exocytosis

Question 15

What is the action of GLUT-4 transporters? [2]

Answer 15

mediates the peripheral action of insulin / and allows uptake of glucose into muscle and adipose tissue cells

Question 16

How are GLUT-4 transporters inserted into the cell membrane of target cells? [2]

Answer 16

1. binding of insulin to insulin receptors results in activation of tyrosine kinase and initiation of cascade response
2. migration of GLUT-4 transporters to the cell surface membrane and increased glucose uptake into the cell