3: Insulin production, secretion and action Flashcards

1
Q

Insulin helps with homeostasis of what?

A

Blood glucose concentration

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2
Q

What is the normal blood glucose concentration?

A

5mmol/L

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3
Q

What cells in the pancreas produce insulin?

A

Beta cells

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4
Q

What cells in the pancreas produce glucagon?

A

Alpha cells

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5
Q

The majority of pancreatic cells are acinar cells which secrete ___ enzymes.

A

digestive enzymes

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6
Q

Where specifically in a beta cell is insulin produced?

A

Rough ER

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7
Q

The precursor of insulin is a large chain polypeptide called ___.

A

preproinsulin

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8
Q

What activates insulin?

A

Cleavage of C peptide which is found in the middle of preproinsulin

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9
Q

Which bonds connect the two polypeptide chains of activated insulin?

A

Disulphide bonds

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10
Q

Which structure connect the two polypeptide chains for inactive proinsulin?

A

C peptide

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11
Q

Depending on the position of amino acids, insulin can be ___-acting or ___-acting.

A

short acting

long acting

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12
Q

Which type of insulin acts ultra-quickly and is injected by T1 diabetics 15 minutes before meals?

A

Lispro

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13
Q

Which type of insulin acts over an ultra-long period and is injected by diabetics at bedtime to maintain their blood glucose level overnight?

A

Glargine

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14
Q

What activates the secretion of insulin by beta cells?

A

Presence of glucose

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15
Q

By which transporter do glucose molecules enter beta cells?

A

GLUT2

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16
Q

Within beta cells, glucose is phosphorylated by ___ to form what?

A

glucokinase

Glucose-6-phosphate

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17
Q

In Type 1 diabetes, what happens to beta cells?

A

Destroyed by immune system

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18
Q

In Type 2 diabetes, why does insulin resistance develop?

A

Beta cells fail to sense glucose because they are constantly surrounded by it (hyperglycaemia), no longer produce insulin

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19
Q

What is produced by the metabolism of one molecule of glucose?

A

36 ATP molecules

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20
Q

When ATP is produced in a beta cell, what happens to

a) Potassium channels
b) Calcium channels

A

K+ channels close

Beta cell depolarises

Ca2+ channels open

Triggers secretion of insulin by exocytosis

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21
Q

Beta cells release insulin in response to blood glucose concentration rising above __ mM.

A

5 mM

22
Q

In hyperglycaemia, the blood glucose concentration is (below / above) the KM of glucokinase.

What does this cause?

A

above KM of glucokinase

Over time, Type 2 diabetes:

hyperglycaemia > hyperinsulinaemia > insulin resistance > hyperglycaemia causing complications via Poyol pathway in a vicious cycle

23
Q

Release of insulin occurs in ___ phases.

A

two phases

24
Q

What percentage of insulin vesicles are immediately available for release from beta cells?

A

About 5%

25
Q

The other 95% of insulin is released in the (first / second) phase of insulin release.

A

second phase

26
Q

What type of drug mimics ATP to depolarise beta cells and trigger insulin release?

A

Sulphonylureas

-amides and -azides

27
Q

What channel do suphonylurea drugs bind to?

A

Potassium channels

cause them to close - depolarisation due to lack of K efflux - Ca influx - insulin release

28
Q

What drug has the opposite effect on potassium channels to sulphonylamides and is used to treat functional tumours like insulinomas?

A

Diazoxide

29
Q

Mutations in the genes for the potassium channels of beta cells can lead to what type of diabetes?

What drug is used to treat this?

A

Neonatal / congenital diabetes

Sulphonylureas

30
Q

What disease is caused by mutations affecting beta cell function and presents like T2 diabetes i.e problems with insulin secretion in young people?

A

MODY

maturity-onset diabetes of the young

31
Q

In type 2 diabetes and MODY, what enzyme’s function is rubbish?

A

Glucokinase

32
Q

What test allows you to tell MODY apart from Type 1 diabetes?

What is the difference?

How is each treated?

A

Genetic testing

MODY resembles T2 in that mutation affects K channels and glucokinase doesn’t work due to hyperglycaemia, T1 diabetes is an autoimmune disease destroying beta cells

MODY - sulphonylureas

T1 DM - insulin injections

33
Q

By what process is insulin’s hormonal signal carried into a cell?

A

Signal transduction

34
Q

What type of hormone receptor does insulin bind to?

A

Receptor tyrosine kinases

35
Q

What is insulin resistance?

A

Change in cell sensitivity to insulin

can be caused by hyperinsulinaemia secondary to hyperglycaemia - cells are surrounded by insulin constantly so they stop responding to it

36
Q

Insulin resistance is a result of problems with insulin ___ and ___.

A

insulin SENSING and SIGNALLING

37
Q

What are the two main weight-related causes of insulin resistance?

A

Obesity (loads of adipose tissue)

Little/no adipose tissue

38
Q

T2 DM has a multifactorial basis - what are these factors?

A

Genetic mutations

Obesity

Insulin resistance

39
Q

What rare, autosomal recessive disease causes growth retardation, a strange facial appearance and absence of subcutaneous fat?

What causes it?

A

Leprechaunism / Donohue syndrome

Mutations in gene for insulin receptors, causing insulin resistance

40
Q

What autosomal recessive condition has a stupid name and features acanthosis nigricans (hyperpigmentation)?

A

Rabson Mendenhall syndrome

Caused again by mutations for insulin receptors, causes insulin resistance

41
Q

What is a fatal condition caused by uncontrolled diabetes?

A

Diabetic ketoacidosis

42
Q

What are the symptoms of diabetic ketoacidosis?

A

Vomiting

Dehydration

Tachycardia

Sweet-smelling breath

43
Q

Diabetic ketoacidosis is usually a complication of (Type 1 / Type 2) diabetes.

A

Type 1 diabetes

44
Q

What are ketones produced by?

A

Fatty acid oxidation

45
Q

What inhibits the oxidation of fat and prevents overload of ketone bodies?

A

Insulin

46
Q

Ketones change the ___ of the blood.

A

pH

47
Q

Fatty acids are converted into ___ ___.

If cells are “starved” of glucose, this chemical is then converted into ___ ___.

A

Acetyl CoA > Ketone bodies

48
Q

Diabetic ketoacidosis usually occurs in Type (1 / 2) diabetes.

A

Type 1 diabetes

49
Q

Untreated diabetic ketoacidosis leads to ___ and death.

A

coma

50
Q

How is DKA treated?

A

Insulin

Rehydration