Questions on regulation of blood glucose and diabetes mellitus

Question 1

Describe how a rise in blood glucose concentration causes a beta cell in an islet of Langerhans to secrete insulin.

Accepted Answer

B1 more glucose enters the beta cell through its transporter protein and is phosphorylated and respired B1 the concentration of ATP in the cytoplasm therefore rises, in proportion to how much glucose the cell is respiring B1 ATP binds to the potassium channels in the cell surface membrane and closes them, so potassium ions can no longer diffuse out B1 positive charge builds up inside and the membrane depolarises, which opens voltage-gated calcium channels and calcium ions diffuse in A1 the calcium causes vesicles of insulin to fuse with the cell surface membrane and release their contents by exocytosis

Question 2

A person has a single fasting blood glucose reading of 7.3 mmol dm⁻³, just above the 7.0 mmol dm⁻³ diagnostic threshold, and no symptoms. Their doctor immediately diagnoses type 2 diabetes on this result alone. Evaluate this diagnosis.

Accepted Answer

B1 in support: 7.3 mmol dm⁻³ fasting is above the World Health Organization threshold of 7.0 mmol dm⁻³, the internationally used cut-off for a raised fasting glucose B1 in support: blood glucose is normally held within a narrow range by insulin and glucagon acting antagonistically, so a reading persistently above that range does suggest the control mechanism has failed B1 against: in a person without symptoms, diagnosis should rest on a repeat test on a different day rather than a single reading, because glucose concentration varies with recent food, illness, stress and timing B1 against: a reading only just above the threshold, with no symptoms such as thirst or weight loss reported, gives less certainty than a reading far above it or one accompanied by symptoms B1 judgement: the diagnosis is premature; the result is concerning enough to warrant repeating the test on another day before diabetes is confirmed, rather than diagnosing from one borderline reading alone

Question 3

Explain how insulin lowers the concentration of glucose in the blood, making clear why it is wrong to say that insulin converts glucose into glycogen.

Accepted Answer

B1 insulin binds to receptors on liver, muscle and adipose cells; it is a signal and never touches a glucose molecule, and the conversions are done by enzymes inside those cells B1 vesicles carrying glucose transporter proteins fuse with the cell surface membrane, so more glucose enters by facilitated diffusion B1 insulin activates the enzymes of glycogenesis, so glucose entering liver and muscle cells is stored as glycogen, and it also raises the rate of respiration of glucose and promotes its conversion into fat A1 it inhibits the alpha cells at the same time, so the opposing glucagon signal is switched off and less glucose is released from the liver

Question 4

Compare type 1 diabetes with type 2 diabetes, referring to the cause of each, the insulin present in the blood, how each is usually managed and why age at onset does not separate them.

Accepted Answer

B1 in type 1 the beta cells have been destroyed by the person's own immune system, whereas in type 2 the target cells respond poorly to insulin and secretion may fall later B1 in type 1 little or no insulin is produced, whereas in type 2 insulin is produced, sometimes in excess, but the receptors respond weakly to it B1 type 1 must be managed with insulin injections matched to meals and exercise, whereas type 2 is usually managed first by diet, weight loss and exercise, with drugs and sometimes insulin later B1 the two are separated by cause and not by age: type 2 is regularly diagnosed in teenagers and type 1 can begin at fifty

Question 5

In a glucose tolerance test a person's blood glucose concentration is 5.6 mmol dm⁻³ when fasting, rises to 9.8 mmol dm⁻³ at 30 minutes, and has returned to 5.6 mmol dm⁻³ at 120 minutes. Calculate the percentage increase in concentration between fasting and 30 minutes, and calculate the mean rate of fall between 30 and 120 minutes.

Accepted Answer

M1 the increase is 9.8 − 5.6 = 4.2 mmol dm⁻³ M1 percentage increase is the increase divided by the starting value and multiplied by 100, so 4.2 ÷ 5.6 × 100 A1 75 per cent A1 the fall of 4.2 mmol dm⁻³ takes 90 minutes, so the mean rate is 4.2 ÷ 90 = 0.047 mmol dm⁻³ min⁻¹

Question 6

Insulin has to be injected rather than swallowed. Suggest why, and suggest why a person with type 2 diabetes can often control their blood glucose by diet and exercise alone while a person with type 1 cannot.

Accepted Answer

B1 insulin is a protein, and a protein that is swallowed is hydrolysed by proteases in the stomach and small intestine B1 it would be broken down into amino acids, which are absorbed but have none of the effects of the hormone, so it must enter the blood without passing through the gut B1 in type 2 diabetes the beta cells still secrete insulin, so reducing the glucose load of meals and losing weight can improve how well the target cells respond and let the person's own insulin cope A1 in type 1 the beta cells have been destroyed, so there is no insulin to improve the response to, and the hormone itself has to be replaced

Question 7

Explain how a test strip carrying immobilised glucose oxidase and peroxidase measures the concentration of glucose in a drop of blood, and explain why the strip does not respond to other sugars.

Accepted Answer

B1 glucose oxidase catalyses the oxidation of glucose to gluconic acid, and hydrogen peroxide is also produced B1 peroxidase then catalyses a reaction between that hydrogen peroxide and a colourless chromogen, turning it into a coloured product B1 the more glucose there was, the more hydrogen peroxide is made and the deeper the colour, which is compared with a printed chart, so the reading is a range rather than an exact value A1 only glucose is complementary to the active site of glucose oxidase, so no other sugar in the sample is oxidised and none produces any colour

Question 8

Compare the two responses in the table, quoting figures, and explain what person B's results suggest about their control of blood glucose.

Accepted Answer

B1 person B starts at 8.2 mmol dm⁻³ against 4.8 for person A, so B's fasting concentration is already well above the normal range B1 B peaks higher and later, at 14.6 mmol dm⁻³ at 60 min against 7.6 at 30 min for A B1 A is back to its starting concentration by 150 min, whereas B is still at 11.4 mmol dm⁻³ and has fallen by only 3.2 from its peak A1 B's glucose is removed from the blood slowly, so B either secretes too little insulin or B's cells respond poorly to it; glucose values alone cannot tell type 1 from type 2

Question 9

Explain why a blood glucose concentration far below normal is dangerous within minutes, and explain why a blood glucose concentration far above normal is dangerous only over a longer period.

Accepted Answer

B1 nervous tissue respires almost exclusively on glucose and stores none of its own, so a severe fall quickly starves neurones of respiratory substrate B1 that danger develops within minutes because the brain has no store of its own to fall back on while blood glucose is being corrected B1 a very high concentration lowers the water potential of the blood, so water moves out of cells by osmosis, and once the kidney's reabsorption carriers are saturated glucose appears in the urine A1 that glucose in the urine drags water out with it by osmosis, so a persistently high concentration causes dehydration, thirst and copious urination over hours to days rather than minutes

Question 10

Describe how glucagon raises the concentration of glucose in the blood, and describe why a rise in muscle glycogen breakdown does not have the same effect.

Accepted Answer

B1 glucagon binds to receptors on hepatocytes and, through the same cyclic AMP cascade as adrenaline, activates glycogen phosphorylase, so glycogen is broken down to glucose B1 glucagon also activates the enzymes of gluconeogenesis in the liver, so glucose is made from non-carbohydrate sources as well as released from stores B1 muscle cells also break down glycogen when activated by adrenaline, but they lack the enzyme glucose-6-phosphatase A1 without that enzyme, muscle cells cannot convert the phosphorylated glucose produced back into free glucose able to leave the cell, so muscle glycogen supplies the muscle itself rather than raising blood glucose

Question 11

A person has fasted for three days. Suggest what has happened to their liver glycogen stores by this point, and suggest why their blood glucose concentration can still be close to normal.

Accepted Answer

B1 liver glycogen stores are largely depleted well before three days, since they are exhausted within about a day of fasting beginning B1 with little glycogen left, glycogenolysis can no longer supply much glucose to the blood B1 gluconeogenesis in the liver becomes the main source instead, converting amino acids from protein breakdown and glycerol from fat breakdown into glucose A1 glucagon secretion rises as blood glucose starts to fall, and it promotes both glycogenolysis while it lasts and gluconeogenesis, which is what keeps the concentration close to normal despite no food being eaten

Question 12

Name the cells that secrete insulin and the cells that secrete glucagon, and name the patches of tissue in the pancreas that contain both kinds of cell.

Accepted Answer

B1 beta cells secrete insulin B1 alpha cells secrete glucagon B1 both are found in the islets of Langerhans, the endocrine tissue scattered through the pancreas

Question 13

A biosensor for blood glucose gives a numerical reading rather than a colour to compare against a chart. Explain how the biosensor converts the concentration of glucose in a blood sample into that number.

Accepted Answer

B1 glucose oxidase immobilised on the electrode catalyses the oxidation of glucose, and this reaction releases electrons B1 the electrode collects those electrons, so an electric current flows that is proportional to the concentration of glucose in the sample A1 a processor built into the meter converts that current into a number displayed in millimoles per cubic decimetre

Question 14

Complete each statement below with the correct term from glycogenesis, glycogenolysis and gluconeogenesis: (a) the synthesis of glycogen from glucose is called ___; (b) the breakdown of glycogen to glucose is called ___; (c) the production of glucose from amino acids or glycerol is called ___.

Accepted Answer

B1 (a) glycogenesis, the synthesis of glycogen from glucose B1 (b) glycogenolysis, the breakdown of glycogen to glucose B1 (c) gluconeogenesis, the production of glucose from non-carbohydrate sources

Question 15

State the normal blood glucose concentration in mmol dm⁻³, and state one source, other than a meal, from which glucose can enter the blood.

Accepted Answer

B1 about 4 to 6 mmol dm⁻³, commonly quoted as roughly 5 mmol dm⁻³ B1 glycogenolysis in the liver, or gluconeogenesis from non-carbohydrate sources such as amino acids or glycerol