Control of Blood Glucose

Why is glucose homeostasis important?

CNS almost entirely dependent on glucose as source of energy (also for erythrocytes). Blood glucose concentrations fluctuate in fed and fasting state. Too low and too high concentrations are harmful

1 of 60

Where does glycolysis take place in a cell?

In the cytosol

2 of 60

Why do erythrocytes not use fats as a source of energy?

No mitochondria present in erythrocyte for lipid metabolism

3 of 60

What is the physiological circulating glucose concentration?

3.9-6.1 mM (precise value - plot of fasting blood glucose and insulin complications - see changes/complications after 6.2 mM) - important to avoid long term complications of diabetes

4 of 60

What are the glucose concentration during average fasting in most adults?

4.4-5 mM (able to maintain blood glucose levels despite fasting for a long time)

5 of 60

What happens if the glucose concentration drops to 2.5 mM or less?

Results in coma or death (hypoglycaemia - medical emergency)

6 of 60

What happens if the glucose concentration rises for an extended time?

Can also result in coma and death (hyperglycaemia - not as serious as hypoglycaemia)

7 of 60

Describe features of hypoglycaemia

Harmful to the CNS, insufficient fuel, causes dizziness and drowsiness, can lead to a coma. Insufficient fuel in erythrocytes can lead to membrane rupture which compromises the delivery of oxygen to tissues (give sugar/food to a diabetic patient)

8 of 60

Describe features of hyperglycaemia (1)

Harmful to CNS, osmotic loss of cell water, leads to dehydration, hypersmolar coma. Hyperglycaemia causes malfunction of several tissues (glycosylation of proteins)

9 of 60

Describe features of hyperglycaemia (2)

Above certain level, kidney cannot reabsorb glucose (dissolved in extracellular fluid and excreted, symptoms of thirst and frequent urination)

10 of 60

Do all reactions of glucose involve enzymes?

No. Glucose can bind to proteins (HbA1c - monitor glucose levels over long period, 2-3 months, normal level <7%, depends on baseline))

11 of 60

What is the average lifespan of an erythrocyte?

120 days

12 of 60

What are the units for plasma glucose?

mmol (10^-3)

13 of 60

Describe the trend for glucose, insulin and glucagon in a normal person over 24 hours of normal eating behaviour (mixed meals) (1)

Glucose levels increases after having meals (returns to normal levels within 2 hours). Glucagon has an opposite trend to plasma glucose levels. As glucose levels increase, insulin levels increases, when glucose levels decreases, insulin decreases

14 of 60

Describe the trend for glucose, insulin and glucagon in a normal person over 24 hours of normal eating behaviour (mixed meals) (2)

Concentration of hormone is lower than the metabolite (10^-9)

15 of 60

What are the general trends for glucose, insulin and glucagon after a high carbohydrate meal?

Glucose increases then returns to normal levels within 2 hours. Insulin secretion increases. Glucagon secretion decreases

16 of 60

Describe the role of the liver and pancreas

Location of pancreatic islets reflects their functional role. Pancreas sends response to liver. Liver can break down glucose or synthesis glycogen. Quick responses

17 of 60

Insulin is released from which cells?

Beta cells (insulin - glucose lowering hormone)

18 of 60

Glucagon is released from which cells?

Alpha cells (lack of glucagon should lead to hypoglycaemia)

19 of 60

Which hormones are the prime regulators of blood glucose concentrations?

Insulin and glucagon

20 of 60

What is the effect of adrenaline (from the adrenal medulla) on glucose levels?

Adrenaline inhibits insulin secretion which results in glucose levels increases

21 of 60

What is the effect of cortisol (from the adrenal cortex) on glucose levels?

The stress hormone increases glucose levels (patients on corticosteroids have higher glucose levels)

22 of 60

What is the effect of growth hormone (from the anterior pituitary) on glucose levels?

Excessive levels result in high blood glucose levels

23 of 60

What is an exocrine organ?

Secretes digestive juices/enzymes via a duct (e.g. pancreas)

24 of 60

What is an endocrine organ?

Secretes hormones into the bloodstream (response through hormone receptors)

25 of 60

Which cells in the body has an insulin receptor?

Every cell in the body as an insulin receptor

26 of 60

Describe features of the Islets of Langerhans

Endocrine part of pancreas. 2% of total pancreatic mass. Adult pancreas contains about 1 million islets. Beta cells (60-70%) secrete insulin, alpha cells (30-40%) secrete glucagon, delta cells secrete somatostatin

27 of 60

Describe features of insulin synthesis (1)

Nucleus (transcription of pre-pro-insulin mRNA). RER (translation of pre-pro-insulin and cleavage to proinsulin). Golgi (package into secretory granules with processing enzymes). Secretory granules (conversion of proinsulin into insulin, C-peptide)

28 of 60

Describe features of insulin synthesis (2)

Insulin in crystals with Zn2+ until secretion

29 of 60

Outline the processing of pro-insulin into insulin and C-peptide (1)

Pro-insulin is one long polypeptide chain. Disulphide bridges in insulin prohormone. In mature insulin there are 2 polypeptide chains, 1 intrachain and 2 disulphide bridges. Insulin is not active in the presence of C-peptide

30 of 60

Outline the processing of pro-insulin into insulin and C-peptide (2)

C-peptide has no physiological function. Measure C-peptide - know level of endogenous production of insulin

31 of 60

Describe the control of insulin secretion from the pancreatic beta cell

Insulin secreted when glucose is high, glucose into beta cell, metabolised, produces ATP, causes K+ channels to close on the cell membrane, causes depolarisation of the membrane, Ca channels open, Ca influx, triggers exocytosis of insulin (secretion)

32 of 60

What could be the issues with the control of insulin secretion?

Not secreting enough insulin. Secretion of insulin but with no effect/response with receptor (possible to close K+ channel artificially to cause Ca influx and insulin secretion)

33 of 60

Which factors stimulate insulin secretion?

A rise in blood glucose, rise in amino acid concentration in blood. Gut hormones (secretin/other GI hormones released after food intake before blood glucose is elevated). Glucagon (providing fine tuning of blood glucose homeostasis)

34 of 60

Insulin secretion is inhibited by which hormone?

Adrenaline

35 of 60

Which factors stimulate glucagon secretion?

Low blood glucose. High concentration of amino acids in the blood (prevents hypoglycaemia after protein meal). Adrenaline (in periods of stress, glucagon secretion is stimulated regardless of blood glucose, insulin secretion suppressed)

36 of 60

What are the sites of insulin action and metabolism? (1)

Glucose converted to fatty acids (store in adipocyte). Glucose converted into glycogen (stored in muscle). Glucose converted into glycogen in liver (store - can convert to lipids in adipocyte). Amino acids stored in muscle/liver cells

37 of 60

What are the sites of insulin action and metabolism? (2)

Conversion of glucose to fatty acids when glucose levels are high. Cannot convert fatty acids to glucose. Insulin activated fatty acid synthesis activation pathway. Fatty acids stored in periphery. Insulin inhibits fat breakdown

38 of 60

What are the sites of glucagon action and metabolism? (1)

Glucagon converts glycogen to glucose, no fatty acid conversion, no store f muscle protein (but store for fat)

39 of 60

Outline the biochemical pathway for glucose (brain: fed or fasting)

Glucose, glc-6-p, pyruvate, ace CoA, TCA, OX PHOS, ATP

40 of 60

Outline the biochemical pathway for glucose (erythrocyte: fed or fasting)

Glucose, glc-6-p, pyruvate, lactate

41 of 60

What are the metabolic effects of insulin the liver?

Inhibition of gluconeogenesis. Activation of glycogen synthesis (glycogen synthase activated). Increased fatty acid synthesis and lipid assembly. Increased amino acid uptake and protein synthesis

42 of 60

What are the metabolic effects of insulin the muscle?

Increases glucose uptake by increasing glucose transporters. Increased amino acid uptake and protein synthesis. Activation of glycogen synthesis (glycogen synthetase activated)

43 of 60

Outline the biochemical pathway for glucose (muscle: fed or fasting)

Glucose, glc-6-p, glc-1P, glycogen

44 of 60

What are the metabolic effects of insulin adipose tissue?

Uptake of fatty acids and storage as TAG (lipoprotein lipase activated). Inhibition of lipolysis by adipose tissue (hormone sensitive lipase inhibited). Increased uptake of glucose into adipocytes to provide glycerol phosphate for TAG assembly

45 of 60

What are the metabolic effects of glucagon? (1)

Increase in blood glucose (increased glycogenolysis and gluconeogenesis in liver). Increase in circulating fatty acids and ketone bodies (increase adipose tissue lipolysis increased fatty acid oxidation in liver and ketone body formation)

46 of 60

What are the metabolic effects of glucagon? (2)

Decrease in plasma amino acids (increased uptake by liver for gluconeogenesis)

47 of 60

What are the metabolic effects of glucagon? (3)

(Graph). Stop eating - first use liver glycogen (24 hours), start gluconeogenesis (stop eating, only drink water - last for 40 days)

48 of 60

Describe features of adrenaline

Mobilises fuel during stress. Stimulates glycogenolysis (muscle and liver). Stimulates fatty acid release from adipose tissue

49 of 60

Describe features of cortisol

Provided for long term requirements. Stimulates amino acid mobilisation from muscle. Stimulate gluconeogenesis. Stimulates fatty acid release from adipose tissue

50 of 60

Describe features of diabetes mellitus

Affects 6% of UK population - 4 million, continues to increase. 90% of all endocrine disorders. Major cause of blindness, amputations, premature deaths. 5-10% of total health care budget (2.5 billion)

51 of 60

What are the types of diabetes?

Type 1 and type 2 (10% of diabetics in the UK are type 1)

52 of 60

Describe features of glucose tolerance curves of normal and diabetic subjects

Obesity related to type 2 diabetes. DM increases beyond renal threshold of 10 mmol (kidneys unable to reabsorb glucose, excreted in urine). Female patients on the pill may have impaired glucose intolerance

53 of 60

Describe features of type 1 diabetes

Autoimmune destruction of beta cells. Early onset. Polyuria, polydipsia, polyphagia, fatigue, weight loss, muscle wasting, weakness. Hyperglycaemia and ketoacidosis. Need insulin treatment

54 of 60

Describe features of type 2 diabetes (1)

Usually later onset. Insulin resistance (target tissues non-response). Usually milder than type 1. Association with diet and lifestyle e.g. obesity. Major increase in incidence (children). Hyperglycaemia but no ketoacidosis

55 of 60

Describe features of type 2 diabetes (2)

Often responds to diet and oral hypoglycaemic agents

56 of 60

What are the chronic complications of diabetes mellitus? (1)

Microangiopathy (changes in walls of small blood vessels seen as thickening of basement membrane). Retinopathy (blindness is 25 more common in diabetic patients). Nephropathy (renal failure 17x more common)

57 of 60

What are the chronic complications of diabetes mellitus? (2)

Neuropathy (postural hypotension, impotence, foot ulcers

58 of 60

What is the treatment for type 1 diabetes?

Exogenous insulin by injection. Important to balance dosage with amount of food to avoid hypoglycaemia incidents (most common complication of insulin therapy)

59 of 60

What is the treatment for type 2 diabetes?

Weight reduction, dietary modification, oral hypoglycaemic agents. Biguanides (increase number of GLUT4). Sulphonylureas (act on beta cell to improve insulin secretion)

60 of 60

Get Revising

Control of Blood Glucose

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Similar Pharmacy resources:

Other cards in this set

Card 2

Front

Back

Card 3

Front

Back

Card 4

Front

Back

Card 5

Front

Back

Comments

Related discussions on The Student Room

Similar Pharmacy resources: