The Endocrine Pancreas Flashcards
1
Q
Energy (food) intake is determined by the balance of activity in which two hypothalamic centres?
A
Feeding centre
Satiety centre
2
Q
What does the feeding centre promote?
A
Feelings of hunger and drive to eat
3
Q
What does the satiety centre promote?
A
Feelings of fullness by suppressing feeding centre
4
Q
Two theories about how we control feeding and satiety centres
A
Glucostatic theory
Lipostatic theory
5
Q
What is the Glucostatic theory?
A
Food intake is determined by blood glucose; as [BG] increases, the drive to eat decreases (- feeding centre, + satiety centre)
6
Q
What is the lipostatic theory?
A
Foot intake is determined by fat stores; as fat stores increase, the drive to eat decreases (- feeding centre, + satiety centre).
7
Q
What is a hormone released by fat stores/adipose tissue and what does it do?
A
Leptin
Depresses feeding activity
8
Q
3 categories of energy output
A
Cellular work
Mechanical work
Heat loss
9
Q
What counts as mechanical work?
A
Movement either on large scale using muscle or intracellularly
10
Q
What counts as cellular work?
A
Transporting molecules across membranes
growth and repair
storage of energy (e.g. fat, glycogen, ATP synthesis)
11
Q
What is metabolism?
A
Integration of all biochemical reactions in the body
12
Q
3 elements of metabolism
A
- extracting energy from nutrients in food
- storing that energy
- utilising that energy for work
13
Q
What is an anabolic pathway?
A
Build up - net effect of synthesis of large molecules from molecules of smaller size, usually for storage purposes
14
Q
What is a catabolic pathway?
A
Break down - net effect is degradation of large molecules into smaller ones, releasing energy for work
15
Q
Example of a catabolic pathway
A
Glucocorticoid pathway
16
Q
What state do we enter into after eating and what happens during this?
A
Absorptive state
Ingested nutrients supply the energy needs of the body and the excess is stored.
17
Q
What type of pathway is the absorptive state?
A
Anabolic
18
Q
What dominates the anabolic phase?
A
Insulin
19
Q
When do we enter the post-absorptive state / fasted state?
A
Between meals
Overnight
20
Q
What happens during the post absorptive / fasted state?
A
The pool of nutrients in the plasma decreases
We rely on body stores to provide energy, releasing this energy
21
Q
What kind of phase is the post absorptive / fasted state?
A
Catabolic phase
22
Q
What dominates the post absorptive / fasted phase?
A
Glucagon
23
Q
What is the brains only energy supply?
A
Glucose
24
Q
How is the concentration of blood glucose maintained?
A
From glycogen (glucogenolysis) or amino acids (gluconeogenesis)
25
What effects does hypoglycaemia lead to in the brain?
Coma
| Death
26
What is the only organ in the body which has access to blood glucose when the concentration of blood glucose falls below normal range?
The brain
27
What can be stored as fat?
Glycerol as fatty acids
| Glucose if excess glucose
28
What is fat broken down into?
Free fatty acids
29
What are carbohydrates broken down into?
Glucose
30
How Is excess glucose stored in normal circumstances?
Glycogen in muscle or liver
| Triacylglycerols (TAG) in liver and adipose tissue
31
What is lipogenesis and glycogenesis stimulated by?
Insulin
32
What is gluconeogenesis and glycogenosis stimulated by?
Glucagon
33
What happens if we become short of glucose?
Glycogen stores are broken down and new glucose is created from amino acids - glucogenosis and glyconeogenesis
34
What is required to metabolise glucose?
Insulin
35
Normal range of [BG]
4.2 - 6.3mM (80-120mg/dl) / 5 mM
36
What [BG] is classified as hypoglycaemia?
< 3 mM
37
What two hormones produced in the pancreas are key to the maintenance of a tight range of [BG]?
Insulin
| Glucagon
38
How much of the pancreas works as an exocrine gland and how much as an endocrine gland?
99% as exocrine - releasing enzymes and NaHCO3 via ducts into alimentary canal to support digestion
1% has endocrine function
39
Where are the hormones produced in the pancreas?
Islets of Langerhans
40
What are the 4 types of islet cells in the pancreas?
A cells
B cells
Gamma cells
F cels
41
What do A islet cells produce?
Glucagon
42
What do B islet cells produce?
Insulin
43
What do gamma islet cells produce?
Somatostatin
44
What do F islet cells produce?
Pancreatic polypeptide
45
What type of hormone is insulin?
Peptide hormone
46
Function of insulin
Stimulates glucose uptake by cells
47
What is insulin originally synthesised as and what is this converted into?
A large preprohormone - preproinsulin which is then converted to proinsulin in the ER
48
How is proinsulin stored?
Packaged as granules in secretory vesicles.
| When cleaved stored as insulin and C peptide until activation and secretion occurs
49
What is proinsulin cleaved into?
Insulin and C peptide
50
What is the only hormone which lowers the [BG]?
Insulin
51
What do most cells use as their energy source during the absorptive state?
Glucose
52
What are excess amino acids converted into?
Fat
53
How are fatty acids stored?
In the form of triglycerides in adipose tissue and liver
54
What type of hormone is glucagon?
Peptide hormone
55
What is the main function of glucagon?
To raise blood glucose
56
What does glucagon mainly act on?
The liver
57
Control of blood glucose depends on the balance between what two hormones?
Insulin
| Glucagon
58
What processes happen in blood when insulin dominates in the fed state?
Increased glucose oxidation
Increased glycogen synthesis
Increased fat synthesis
Increased protein synthesis
59
What processes happen in the blood in the fasted state where glucagon dominates?
Increased glycogenolysis
Increased gluconeogenesis
Increased ketogensis
60
When glucagon dominates, what happens to glucose levels in the blood?
increased glucose levels in plasma as it is released into plasma
61
How is insulin released into the plasma from the islet cells?
When glucose is abundant it enters cells through glucose transport proteins (GLUT) and metabolism increases
This increases [ATP] within the cell causing the KATP channel to close.
Intracellular [K+] rises, depolarising the cell
Voltage dependent Ca2+ channels open and trigger insulin vesicle exocytosis into the circulation
62
What occurs in the blood and the cells for insulin not to be secreted?
When [BG] is low, [ATP] is low and so KATP channels are open so K+ ions flow out removing the +ve charge from the cell and hyperpolarising it
So the voltage gated Ca2+ channels remain closed
so insulin is not secreted
63
What does insulin bind to on the cells?
Tyrosine kinase receptors on the cell membrane of insulin sensitive tissues
64
What are the two insulin sensitive tissues?
Muscle
| Adipose tissue
65
What does insulin stimulate to happen to the cells?
Stimulates mobilisation of specific glucose transporters (GLUT-4)
66
Where does GLUT 4 reside usually?
In the cytoplasm of unstimulated muscle and adipose cells
67
What does GLUT 4 do once stimulated by insulin?
Migrates to the membrane and then transports glucose into the cell
68
What happens to GLUT 4 transporters when the insulin stimulation stops?
They return to the cytoplasmic pool
69
What is the glucose taken up by cells primarily used for?
Energy
70
How much of total body weight does muscle make up?
40%
71
How much of total body weight does fat make up?
20-25%
72
What are other NON-insulin dependent GLUT-transporters and where are they found?
```
GLUT-1 = many tissues e.g. brain, kidney, RBCs
GLUT-3 = similar
GLUT-2 = B cells of pancreas and liver
```
73
How does glucose enter the liver?
Down a concentration gradient through GLUT-2 transporters (NON-insulin dependent)
74
Insulin relationship to liver
Insulin has no direct effect on liver
| Although glucose transport into hepatocytes is affected by insulin status
75
Actions of insulin
Move glucose into cells
Increases glycogen synthesis in muscle and liver (stimulates glycogen synthase and inhibits glycogen phosphorylase)
Increases amino acid uptake into muscle, promoting protein synthesis (anabolic)
Increases protein synthesis and inhibits proteolysis
Increases triacylglycerol synthesis in adipocytes and liver i.e. stimulates lipogenesis and inhibits lipolysis
Inhibits the enzymes of gluconeogenesis in the liver
Has permissive effect on growth hormone
Promotes K+ ion entry into cells by stimulating Na/K ATPase.
76
Approx. half life of insulin and what is it principally degraded by?
5 mins
| Liver and kidneys
77
What happens to insulin bound receptors once insulin action is complete?
They are internalised by endocytosis and destroyed by insulin protease, some recycled
78
What stimuli cause increased insulin release?
```
Increased [BG]
Increased [amino acids] in plasma
Glucagon
Other (incretin) hormones controlling GI secretion and motility e.g. gastrin, secretin, CCK - insulin prevents glucose surge when absorption occurs
Vagal nerve activity
```
79
Stimuli which inhibit insulin release
Low [BG]
Somatostatin (GHIH)
Sympathetic a2 effects
Stress e.g. hypoxia
80
What does oral loading of same amount of glucose compared to IV lead to? Why?
Leads to increased insulin by both direct effect on B cells and vagal stimulation of B cells, plus incretin effects
Because vagal activity stimulates release of major GI hormones as well as insulin release
81
What hormones are part of the glucose counter-regulatory control system?
Glucagon
Epinephrine
Cortisol
GH
82
What are glucagon receptors?
G-protein coupled receptors linked to adenylate cyclase/cAMP system
83
Effects of glucagon
Increased glycogenolysis
Increased gluconeogenesis (substrates amino acids and glycerol)
Formation of ketones from fatty acids (lipolysis)
84
Where do all the processes as a result of glucagon occur?
The liver
85
Secretion of glucagon
Relatively constant
| Increases dramatically when [BG] <5.6mM so doesn't wait until levels are dangerously low
86
What are amino acids a potent stimulus for?
Glucagon secretion
87
What do amino acids in the plasma release?
Both insulin and glucagon
88
What is the brain also known as in endocrine?
Obligatory glucose user
89
What can most other tissues readily use to produce energy?
FFAs
| Ketones
90
Stimuli that promote glucagon release
```
Low [BG]
High [amino acids]
Sympathetic innervation and epinephrine, B2 effects
Cortisol
Stress e.g. exercise, infection
```
91
Stimuli that inhibit glucagon release
Glucose
Free fatty acids (FFAs) and ketones
Insulin (fails in diabetes so glucagon levels rise despite high [BG])
Somatostatin
92
Effect of an increase in parasympathetic activity (vagus) of islet cells
Increase in insulin and to a lesser extent decrease in glucagon, in association with the anticipatory phase of digestion
93
Effect of an increase in sympathetic activation of islet cells
promotes glucose mobilisation -> increase in glucagon, increase in epinephrine and inhibition of insulin, all appropriate for a fight or flight response
94
What type of hormone is somatostatin?
Peptide hormone
95
Where is somatostatin (GHIH) secreted from?
D cells of pancreas
| Hypothalamus
96
What is the main action of the pancreatic somatostatin?
Inhibit activity in the GI tract
97
What does somatostatin suppress the release of in a paracrine fashion?
Both insulin and glucagon
98
What does GHIH inhibit the secretion of from the anterior pituitary?
Growth hormone
99
What happens to the entry of glucose into muscle during exercise?
It is increased during exercise, even in the absence of insulin
100
Effect of exercise on insulin
Increases insulin sensitivity of muscle and causes an insulin-independent increases in the number of GLUT-4 transporters incorporated into the muscle membrane
101
Effects of prolonged exercise on insulin sensitivity
Increases it
102
What are excess fatty acids converted into and by what?
Ketone bodies
| By the liver
103
What do ketone bodies provide as an additional energy source?
Muscle
| Brain
104
After a period of starvation, what does the brain adapt to use?
Ketones
105
How are ketones produced?
Through beta oxidation in the liver from free fatty acids
106
DM involves the loss of control of what?
Blood glucose levels
107
Two types of DM
Type I
| Type II
108
Pathology of Type I DM
Autoimmune destruction of the pancreatic B-cells
| Destroys the ability to produce insulin and seriously compromises the patients ability to absorb glucose from the plasma
109
What % of diabetic patients are insulin dependent?
10%
110
What is T1DM also known as?
Insulin dependent diabetes mellitus (IDDM)
111
What is T2DM also known as?
Non insulin dependent diabetes mellitus (NIDDM)
112
Pathology of type II diabetes
Peripheral tissues become insensitive to insulin = insulin resistance
Muscle and fat no longer respond to normal levels of insulin
Either due to an abnormal response to insulin receptors in these tissues or a reduction in their number
B cells remain intact and appear normal, there may even be hyperinsulinaemia
113
What % of diabetic patients are insulin resistant? (NIDDM)
90%
114
What is T2DM typically associated with?
Obesity
115
What age does T2DM usually appear?
> 40 y/o but age decreasing
116
What are major contributors to T2DM?
High sugar and animal fat diet
| Little exercise
117
Treatment of T2DM
Initial - exercise and dietary changes
If fails - oral hypoglycaemic drugs (metformin)
Sulphonylureas
Eventually may end up taking insulin
118
What is the diagnostic criterion for diabetes?
Hyperglycaemia (elevated [BG])
119
Describe the glucose tolerance test
Patient ingests glucose load after fasting [BG] measured
| [BG] will normally return to fasting levels within an hour, elevation after 2 hours is indicative of diabetes
120
Does the glucose tolerance test distinguish between T1DM and T2DM?
No
121
Pathology of ketoacidosis in T1DM
FFAs can be converted to ketones for additional energy source for muscle and brain when energy sources are scarce
In poorly controlled IDDM a lack of insulin depresses ketone body uptake.
They build up rapidly in plasma and because they are acidic create life threatening acidosis (ketoacidosis) with plasma pH < 7.1
122
How are ketones detectable?
Urine
| Produce distinctive acetone smell to breath
123
What are hyperglycaemic long term diabetic complications?
Retinopathy
Neuropathy
Nephropathy
Cardiovascular disease
