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Flashcards in Diabetes Deck (50)
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1
Q

Describe the different cells making up the Islet of Langerhans and their function

A

A cells = glucagon

B cells = insulin

D cells = somatostatin

PP cells = pancreatic polypeptide

2
Q

What are the main modulators of blood glucose?

A

Insulin

Glucagon

3
Q

Describe the role of insulin in blood glucose control

A

Decreases blood glucose concentration

Metabolism of carbohydrates, fats and proteins

Synthesises enzymes involved in glucose metabolism

Activation of RAS -> activation of MAP kinases -> DNA transcription -> RNA production -> enzyme synthesis

4
Q

What activates insulin release?

A

Glucose

Increases ATP concentration inside B cells

5
Q

Describe the role of glucagon in glucose control

A

Increases concentration of glucose in the blood

6
Q

What processes do glucagon trigger that increase blood glucose concentration?

A

Glycogenolysis

Gluconeogenesis

Inhibition of glycogen synthesis

7
Q

What are the two types of diabetes?

A

Type I

Type II

8
Q

Pathogenesis of type I diabetes

A

B cells are destroyed in an autoimmune process

Insulin replacement therapy is essential

9
Q

Pathogenesis of type II diabetes

A

Individuals are resistant to insulin

Fails to secrete sufficient hormone

10
Q

Symptoms of type II diabetes

A

Wasting due to increased protein breakdown

Ketoacidosis due to increased fat metabolism

Osmotic diuresis due to decreased utilisation of glucose

Damage to blood vesels

Neuropathy

11
Q

Conditions caused by damage to blood vessels due to diabetes mellitus

A

Retinopathy

Nephropathy

12
Q

How does glycosuria and osmotic diuresis present?

A

Thirst

Polydypsia

13
Q

What causes death in diabetes?

A

Ketoacidosis

14
Q

How does ketoacidosis cause death?

A

Lipid metabolism causes the formation of ketones which decreases the pH

Leads to heart failure

15
Q

What is the half-life of insulin following intravenous injection?

A

10 minutes

16
Q

Why is the intravenous route of insulin administration inconvenient?

A

Short half-life

Constant injections are required to maintain a relatively high concentration in the body

17
Q

What are ways to prolong the half-life of insulin?

A

Subcutaneous injection

Insulin hexamer

Protamine

Insulin glargine

Insulin analogues

18
Q

Why can’t insulin be given by mouth?

A

Due to the proteolytic action of digestive enzymes

19
Q

How much longer is the half-life of insulin following subcutaneous injection instead of intravenous injection?

A

From 10 minutes to 2-4 hours

Travels into the blood slower

20
Q

How can an insulin hexamer be produced?

A

Bind insulin to zinc/other ionic metals

21
Q

Why does insulin hexamer have a longer half-life?

A

Cannot diffuse as easily into the bloodstream

The molecule has to break down into simpler monomers to allow for appropriate diffusion

The breakdown prolongs the half-life of insulin

22
Q

Who came up with the idea of using protamine to modify insulin’s half-life?

A

Hans

23
Q

What is protamine?

A

Postively charged nuclear protein

24
Q

How does protamine increase the half-life of insulin?

A

Clusters hexamers together

25
Q

How long is the half-life of insulin using protamine?

A

8-9 hours

26
Q

What is the name of protamine insulin?

A

NPH

Nuclear protamine Hans

27
Q

What was the importance of NPH?

A

Meant the patient would survive the night

28
Q

What technology allows for insulin glargine to be formed?

A

Recombinant technology

29
Q

What are the distinguishing features of insulin glargine?

A

Long acting form

Peak-less

30
Q

How does insulin glargine synthesis not lead to changes in insulin action?

A

Changing the amino acids in the insulin structure changes its activity

But insulin glargine is formed through changing the ends

31
Q

Describe the process of making insulin glargine

A

One aspargine and two arginine molecules are added to the ends

This makes it less soluble

32
Q

How does insulin glargine have a longer half-life?

A

Less soluble in physiologic pH

Through changing the pKa

The insulin therefore acts as a crystal in the body and does not dissolve

Injected once a day

33
Q

What are insulin analogues?

A

Changes the structure of insulin

34
Q

Two insulin analogues

A

Insulin detemir

Insulin lispro

35
Q

How is insulin determir formed?

A

Fatty acid is bound to the lysine amino acid at position B29

36
Q

How does insulin detemir increase the half-life of insulin?

A

B29 amino acid binds to albumin

Insulin slowly dissociates from this complex

37
Q

How is insulin lispro formed?

A

Lysine and proline residues on the C-terminal end of the B-chain are reversed

38
Q

When is insulin lispro used?

A

When insulin is required quickly

Through blocking the formation of insulin dimers and hexamers

Prevents hypoglycemia

39
Q

Insulin forms used for long-term action

A

Insulin glargine

Insulin detemir

40
Q

Insulin form used for quick effect

A

Insulin lispro

41
Q

What are the two main targets of therapy for diabetes?

A

Increasing insulin concentration

Increasing insulin secretion

42
Q

Drugs increasing insulin secretion

A

Sulphonylureas

Metformin

Acarbose

43
Q

On which patients are sulphonylureas effective?

A

Patients with some functioning B cells

44
Q

How do sulphonylureas work?

A

Mimics the action of glucose

  1. Glucose enters beta cells
  2. Converts into ATP
  3. ATP blocks K-ATP channels
  4. Calcium enters and causes insulin release

Blocks K-ATP channels

45
Q

How does metformin work?

A

Increases glucose uptake into tissues

Inhibits gluconeogenesis

46
Q

How does acarbose work?

A

Inhibits a-glucosidase

Delaying the carbohydrate absorption and reducing the rise in blood glucose that follows a meal

47
Q

What is the best treatment for type II diabetes?

A

Exercise

Reversible condition

48
Q

Why does ingestion of glucose cause increased insulin release than intravenous injection of glucose?

A

Autonomic system activation following smell and chewing activates neuroendocrine cells

Secrete peptide GLP1

GLP1 blocks K-ATP channels and increases insulin secretion

49
Q

What are newer hypoglycemic drugs like?

A

Oral forms

50
Q

Examples of newer oral hypoglycemic drugs

A

Meglitinides - block KATP

Thiozolidines - slow decrease in glucose by binding to transcription factor receptor