The Endocrine Pancreas Flashcards Preview

Z OLD ESA 1- Metabolism > The Endocrine Pancreas > Flashcards

Flashcards in The Endocrine Pancreas Deck (146):
1

What is the pancreas?

A large gland

2

Where is the head of the pancreas?

Nestled in the curvature of duodenum

3

How does the pancreas develop embryologically?

As an outgrowth of the foregut

4

What are the functions of the pancreas?

- Produces digestive enzymes secreted directly into duodenum 
- Hormone production

5

What forms the bulk of the pancreas?

Exocrine function

6

Of what nature are the pancreas’ exocrine secretions?

Alkaline

7

Where do the pancreas’ exocrine secretions go?

Into the duodenum

8

How do the pancreas’ exocrine secretions get into the duodenum?

Through the pancreatic duct

9

Where does the pancreas produce hormones?

From Islets of Langerhans

10

How much of the pancreas is endocrine function?

~1%

11

How to the areas responsible for endocrine secretion appear on a micrograph of the pancreas?

As paler pink regions

12

What kind of hormones does the pancreas secrete?

Polypeptide

13

What hormones does the pancreas secrete?

- Insulin 
- Glucagon 
- Somatostatin
- Pancreatic polypeptide (PP)
- Ghrelin

14

What cells secrete insulin?

ß-cells

15

What cells secrete glucagon?

α-cells

16

What cells secrete somatostatin?

Delta cells

17

What cells secrete PP?

F cells

18

What are insulin and glucagon used in the regulation of?

Metabolism of carbohydrates, proteins and fats

19

What is somatostatin used in?

Islet cell secretion regulation

20

What is PP used in?

GI function

21

What does insulin do to blood glucose?

Lowers it

22

What detects high blood glucose?

The pancreas

23

What happens when the pancreas releases insulin?

Fat cells taken in glucose from the blood, achieving normal blood glucose levels

24

What effect does glucagon have on blood glucose?

Raises it

25

How does glucagon raise blood glucose?

Causes liver to release glucose into the blood, achieving normal blood glucose levels

26

What is insulin signalled by?

Feeding

27

What are the target tissues for insulin?

- Liver 
- Adipose
- Skeletal muscle

28

What kind of action does insulin cause?

Anabolic- building

29

What is glucagon signalled by?

Fasting

30

What are the target tissues for glucagon?

#NAME?

31

What kind of actions does glucagon have?

Catabolic

32

What uses glucose at the fastest rate in the body?

Brain

33

What does the brain rely on for its glucose?

Blood

34

What is the brain sensitive to?

Rises or falls in plasma glucose level

35

What does a rise in plasma glucose level cause that the brain is sensitive to?

Increased osmolarity

36

Why does the circulation of glucose in the blood need to be controlled?

The brain doesn’t have it’s own supply of glucose, and so relies on the circulatory system to supply and steady and regular amount

37

What are the normal plasma glucose concentrations?

- Normally 3.3-6mmol/L
- After a meal 7-8mmol/L

38

What is the plasma glucose renal threshold?

10mmol/L

39

What is glucosuria?

When glucose is excreted in urine

40

When is the renal threshold decreased?

In pregnancy

41

When is the renal threshold increased?

In the elderly

42

Are insulin and glucagon water or lipid soluble?

Water

43

How are insulin and glucagon carried?

Dissolved in the plasma

44

Do insulin and glucagon require special transport proteins?

No

45

How long is the half life of insulin and glucagon?

5 mins

46

What happens to insulin and glucagon at target cells?

They interact with cell surface receptors

47

How can a receptor with a hormone bound be inactivated?

It can be internalised

48

What is insulin important in the storage of?

- Carbohydrates
- Protein 
- Fat

49

What does insulin act against?

- Gluconeogenesis 
- Lipolysis 
- Ketone formation

50

Is insulin glycogenic?

Yes

51

What does insulin consist of?

Two unbranched polypeptide chains, connected by 2 disulphide bridges

52

What do the disulphide bridges in insulin ensure?

Stability

53

How many amino acids are there in insulin?

51; 21 α, 30 ß

54

What does insulin start as?

Preproinsulin

55

Why does insulin start as preproinsulin?

Because insulin mRNA is translated as a single chain precursor

56

How is proinsulin generated?

Removal of it’s signal peptide during insertion into the ER

57

What happens to proinsulin within the Golgi?

It is exposed to several specific endopeptidases, which excise the C peptide

58

What does the excision of the C peptide from insulin generate?

Mature form of insulin, and a C peptide

59

What happens to the newly generated insulin and C peptide?

It’s packaged in the Golgi into secretory granules, which accumulate in the cytoplasm. They are now packaged ready for exocytosis

60

What is margination?

When granules move to the cell surface

61

What is the purpose of margination?

The granules are held in preparation within pancreatic ß-cells ready for need of secretion

62

What happens in exocytosis?

Fusion of vesicle membrane with plasma membrane to release the vesicle contents

63

How much of the insulin stored in the pancreas is secreted in a day?

15%

64

Why is the half life of insulin only 5 minutes?

Because there is no carrier

65

What is the stimulus for insulin release?

Increase in glucose in the extracellular fluid

66

How is glucose transported into the ß-cell?

Facilitated diffusion through GLUT2

67

What does an increase in [glucose ecf ] mean?

Increased concentrations of glucose within the ß-cell

68

What happens to glucose once it’s inside the pancreatic ß-cell?

It is phosphorylated by glucokinase

69

What happens once glucose has been phosphorylated?

It goes through glycolysis respiration

70

What is the result of the phosphorylated glucose going through glycolysis respiration?

Increase in ATP:ADP ratio

71

What does the increase in ATP:ADP ratio in the pancreatic ß-cell lead to?

Depolarisation the membrane

72

Why does an increase in ATP:ADP ratio lead to depolarisation of the membrane?

As ATP-sensitive potassium channel (K ATP channels) open, allowing influx of K +

73

What does the K + influx lead to?

Influx of extracellular calcium

74

Why does K + influx lead to an influx of extracellular calcium?

Voltage-gated calcium channels open

75

What does an increase in ECF calcium in the ß-cell trigger?

Exocytosis of insulin-containg secretory granules

76

What are the metabolic insulin effects?

- Increases glucose uptake in target cells and glycogen synthesis 
- Inhibits breakdown of fatty acids

77

How does insulin increase glucose uptake?

Insertion of GLUT4 channel

78

What is the effect of insulin in the liver?

- Increases glycogen synthesis by stimulating glycogen formation and by inhibiting breakdown 
- Inhibits breakdown of amino acids

79

What is the effect of insulin in muscles?

It increases uptake of amino acids, promoting protein synthesis

80

What is the effect of insulin in adipose tissue?

Increases storage of triglycerides

81

Where does insulin bind?

To the insulin receptor on the cell surface

82

What kind of molecule is the insulin receptor?

A dimer

83

What is the structure of the insulin receptor?

Two identical sub-units spanning the cell membrane

84

What are the insulin receptor sub units made up of?

1 α chain and one ß chain, connected by a single disulphide bond

85

Where is the α chain of the insulin receptor?

On the exterior of the cell membrane

86

Where is the ß chain of the insulin receptor?

Spans the cell membrane in a single segment

87

How is the insulin receptor activated?

- α chains move together when insulin is detected, and fold around the insulin 
- Moves the ß chains together
- This makes the ß chains an active tyrosine kinase
- Initiates a phosphorylation cascade, resulting in increase in GLUT4 expression

88

What does the increase in GLUT4 expression mean?

Means cell can take up more glucose

89

What does glucagon do?

Acts to raise blood glucose

90

How does glucagon act to raise blood glucose?

- Glycogenolytic
- Gluconeogenesis 
- Lipolytic
- Ketogenic

91

What does glucagon mobalise?

Energy release

92

What secretes glucagon?

α cells

93

What is glucagon secreted in response to?

Low glucagon levels in α cells

94

Where is glucagon synthesised?

Rough ER

95

What happens to glucagon once it has been synthesised?

It’s transported to Golgi

96

How is glucagon packaged?

In granules

97

Where does glucagon have its main effect?

In the liver

98

What happens following margination of glucagon granules?

They are held at the cell surface until stimulus of low blood glucose is detected by pancreatic α cells

99

What happens once the pancreatic α cells have detected the stimulus of low blood glucose?

The vesicle membrane fuses with the plasma membrane with the release of the vesicle contents, in a process called exocytosis

100

How many amino acids does glucagon have?

29

101

How many polypeptide chains does glucagon have?

1

102

Does glucagon have disulphide bonds?

No

103

What is the result of glucagon having no disulphide bonds?

It’s flexible

104

How does the synthesis of glucagon differ from that of insulin?

It’s simpler

105

What are the effects of glucagon?

- In the liver, it increases the rate of glycogen breakdown
- Stimulates gluconeogenesis pathways 
- Stimulates lipolysis

106

What is the result of glucagon stimulating lipolysis?

Increases plasma fatty acids

107

What is the net effect of glucagon?

Rise in blood glucose levels

108

What effect does an increase in amino acids have?

Increase in insulin and glucagon

109

What effect does an increase in fatty acids have?

Increases insulin

110

What is the effect of an increase in GI tract hormones?

Increase in insulin

111

What is the effect of an increase in adrenaline and noradrenaline?

Decrease in insulin, increase in glucagon

112

How quickly does insulin and glucagon affect glucose uptake in muscle and adipose tissue?

Rapidly

113

How quickly do hormones affect gluconeogenesis and glycogenesis?

Intermediate- in minutes

114

What effect do insulin and glucagon have on lipogenesis?

#NAME?

115

What effect do insulin and glucagon have on ketogenesis?

#NAME?

116

How quickly do hormones affect lipogenesis?

Delayed- takes hours

117

What effect does insulin and glucagon have on amino acid uptake?

#NAME?

118

How quickly do hormones affect amino acid uptake?

Rapidly- seconds

119

What effect does insulin and glucagon have on protein synthesis?

- Increased by insulin 
- Decreased by glucagon

120

How quickly do hormones affect rates of protein synthesis?

Intermediate- minutes

121

What happens if insulin is excessively high?

Hypoglycaemia

122

What happens if insulin is deficient?

Hyperglycaemia

123

What happens if glucagon is excessively high?

Makes diabetes worse

124

What happens if glucagon is deficient?

May contribute to hypoglycaemia

125

What is type 1 diabetes caused by?

An absolute insulin deficiency caused by autoimmune destruction of pancreatic ß-cells

126

What is a relative insulin deficiency?

When the secretory response of ß-cells abnormally slow/small

127

What are the potential aetiologies of type 2 diabetes?

#NAME?

128

How could the insulin receptor mechanism be defective?

Change in receptor number and/or affinity

129

What is meant by defective post-receptor events?

Insulin resistance

130

What happens in insulin resistance?

The tissues become de-sensitive to insulin

131

What is diabetes insipidus?

An uncommon condition that occurs when the kidneys are unable to conserve water as they perform their function of filtering blood

132

What are the main sites of glucose utilisation?

#NAME?

133

What do the main sites of glucose utilisation show in insulin resistance?

Decreased response to normal circulating concentrations of insulin

134

What % of the population does insulin resistance affect?

- ~25% of general population
- ~92% of patients with type 2 diabetes

135

What does insulin result from?

#NAME?

136

What environmental factors can cause diabetes?

- Obesity 
- Sedentary lifestyle

137

Relative to hyperglycaemia and development of type 2 diabetes, when is insulin resistance present?

12+ years before

138

How does insulin resistance develop?

- Initially, ß-cells compensate by increasing insulin production, maintaining normal blood glucose
- Eventually, ß-cells are unable to maintain increased insulin production, leading to impaired glucose tolerance 
- Finally, ß-cell dysfunction leads to relative insulin deficiency, using overt type 2 diabetes

139

Why does insulin deficiency/resistance cause chronic hyperglycaemia?

- In the muscles, insulin decreases the uptake of glucose and glycogenesis 
- In the adipose tissue, insulin decreases uptake of glucose and decreases lipogenesis and esterification 
- In the liver, insulin decreases glycogenesis and glycolysis, and increases gluconeogenesis
If there is no insulin, these things do not happen, causing hyperglycaemia

140

What are the long term complications of hyperglycaemia in the muscle?

The decreased uptake of amino acids and protein synthesis causes an increase in proteolysis, causing muscle wastage

141

What are the long term complications of hyperglycaemia in the adipose?

Decreased esterification leads to increased lipolysis, leading to weight loss

142

What are the long term complications of hyperglycaemia in the liver?

Gluconeogenesis from muscle amino acids, leading to muscle wastage. 
Ketogenesis from adipose tissue fatty acids, leading to ketosis

143

What are the acute metabolic consequences of hyperglycaemia?

- Glucosuria 
- Polyuria 
- Polydipsia

144

What are the chronic consequences of diabetes?

#NAME?

145

What are the microvascular diseases caused by chronic hyperglycaemia?

- Eye disease, including retinopathy 
- Nephropathy in kidneys)
- Neuropathy in peripheral nervous system

146

What macrovascular disease is caused by chronic hyperglycaemia?

- Coronary artery disease
- Stroke 
- Poor peripheral circulation