The Endocrine Pancreas Flashcards
(146 cards)
1
Q
What is the pancreas?
A
A large gland
2
Q
Where is the head of the pancreas?
A
Nestled in the curvature of duodenum
3
Q
How does the pancreas develop embryologically?
A
As an outgrowth of the foregut
4
Q
What are the functions of the pancreas?
A
- Produces digestive enzymes secreted directly into duodenum
- Hormone production
5
Q
What forms the bulk of the pancreas?
A
Exocrine function
6
Q
Of what nature are the pancreas’ exocrine secretions?
A
Alkaline
7
Q
Where do the pancreas’ exocrine secretions go?
A
Into the duodenum
8
Q
How do the pancreas’ exocrine secretions get into the duodenum?
A
Through the pancreatic duct
9
Q
Where does the pancreas produce hormones?
A
From Islets of Langerhans
10
Q
How much of the pancreas is endocrine function?
A
~1%
11
Q
How to the areas responsible for endocrine secretion appear on a micrograph of the pancreas?
A
As paler pink regions
12
Q
What kind of hormones does the pancreas secrete?
A
Polypeptide
13
Q
What hormones does the pancreas secrete?
A
- Insulin
- Glucagon
- Somatostatin
- Pancreatic polypeptide (PP)
- Ghrelin
14
Q
What cells secrete insulin?
A
ß-cells
15
Q
What cells secrete glucagon?
A
α-cells
16
Q
What cells secrete somatostatin?
A
Delta cells
17
Q
What cells secrete PP?
A
F cells
18
Q
What are insulin and glucagon used in the regulation of?
A
Metabolism of carbohydrates, proteins and fats
19
Q
What is somatostatin used in?
A
Islet cell secretion regulation
20
Q
What is PP used in?
A
GI function
21
Q
What does insulin do to blood glucose?
A
Lowers it
22
Q
What detects high blood glucose?
A
The pancreas
23
Q
What happens when the pancreas releases insulin?
A
Fat cells taken in glucose from the blood, achieving normal blood glucose levels
24
Q
What effect does glucagon have on blood glucose?
A
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
