The Endocrine Pancreas Flashcards
1
Q
What are the two theories that aim to explain what induces feelings of hunger / fullness? Brief explanation of each
A
- Glucostatic Theory: food intake is determined by blood glucose concentration, as BG increases, feelings of satiety increase
- Lipostatic Theory: food intake is determined by fat stores, as fat stores increase feelings of satiety increase
2
Q
What are the three categories of energy output?
A
- Cellular Work: transport / growth and repair / storage of energy
- Mechanical Work: movement
- Heat loss
3
Q
What are anabolic and catabolic pathways? When do each of them occur?
A
- Anabolic: build up, ingested nutrients supply body needs and rest is stored
- Catabolic: Break down, reliance on body stores to provide energy
4
Q
What does the brain need for energy?
A
- The brain needs glucose
- Can use ketone bodies in times of starvation
5
Q
How does the body restore low blood sugar to normal levels?
A
- Glycogenolysis: breakdown od glycogen
- Gluconeogenesis: synthesis of glucose from other energy sources
6
Q
What is the normal range for blood glucose?
When is a patient hypoglycaemic?
A
- Normal: 4.2-6.3 mM (80-120 mg/dl)
- Hypo: <3 mM
7
Q
What are the hormone producing cells of the pancreas? How much of the pancreas do they account for?
A
- Islets of Langerhans
- 1% of pancreas, other 99% does digestion
8
Q
What are the types of islet cells and what do they produce?
A
- Alpha cells: produce glucagon
- Beta cells: produce insulin
- Delta cells: produce somatostatin (aka GHIH)
- F cells: produce pancreatic polypeptide (function unknown)
9
Q
Which metabolic processes does insulin initiate?
A
- Glucose oxidation (so glucose can’t move back out of cells)
- Glycogen synthesis
- Fat synthesis
- Protein synthesis
10
Q
Which metabolic processes does glucagon initiate?
A
- Glycogenolysis
- Gluconeogenesis
- Ketogenesis
11
Q
Describe insulin synthesis and secretion from cells
A
- Synthesized as preproinsulin, converted to proinsulin in ER
- Proinsulin packaged into vesicles, where it gets cleaved to insulin + C peptide
- Stored in that form until Beta cell activation & secretion
12
Q
What stimulates insulin secretion?
A
- Blood glucose concentration
- AA’s and FA’s also do but predominantly glc
13
Q
How is excess glucose stored?
A
- As glycogen in the liver and muscle
- As triacylglycerols (TAGs) in liver and adipose tissue
14
Q
Describe the mechanism of insulin secretion by beta cells when blood glucose rises
A
- Abundant glucose enters beta cells via GLUT-2 and metabolism increases
- Beta cells have K channels that are sensitive to [ATP], K(ATP) channels, when glucose enters [ATP] increases
- K(ATP) channels close due to high [ATP], intracellular [K] rises and cell depolarizes
- Depolarization causes voltage dependent Ca channels to open, triggering insulin vesicle exocytosis into circulation
15
Q
Which way does most of the K flow through K(ATP) channels and how does this work in the insulin release mechanism?
A
- Net movement of K out of cell
- When gates close, intracellular K increases, making the charge in the cell more positive, supplying the voltage for depolarization and Ca channel opening
- When gates remain open the cell remains at a negative voltage due to outward flow of K
16
Q
What hormones other than insulin lower blood glucose?
A
None
Insulin is the only hormone that lowers blood glucose
17
Q
Explain how insulin causes insulin sensitive cells to take up more glucose?
A
- Insulin binds tyrosine kinase receptors on cell surface
- Causes mobilization of GLUT-4 transporters to cell membrane
- More GLUT-4 transporters allows more glucose uptake
- When insulin stimulation stops the GLUT-4 transporters return to the cytoplasmic pool
18
Q
Why are most types of tissue NOT insulin dependent? How significant is it that muscle and fat are?
A
- Because other tissues use different GLUT transporters that do not depend on insulin for recruitment to the cell membrane
- Fat 20-25% BW, muscle about 40% - it’s significant
19
Q
What types of GLUT transporters are found on different cell types?
A
- GLUT 1 & 3: basal glucose uptake in many tissues (eg. brain, kidneys and RBC)
- GLUT 2: Beta cells of pancreas and liver
- GLUT 4: muscle and adipose tissue
20
Q
Is glucose transport into the liver insulin dependent?
A
- No, uses GLUT 2 transporters so glucose moves with concentration gradient
Glucose transport in the liver is affected by insulin though………..
21
Q
How does insulin affect glucose transport in liver cells?
A
- If insulin is bound, hexokinase is activated, phosphorylates glucose so it can’t move out via GLUT 2 and creates a concentration gradient favouring glucose movement into the cell
- If insulin is not bound the liver synthesizes glucose via glycogenolysis and gluconeogenesis, creating a high intracellular [glc] so glucose moves out of the cell
22
Q
Additional mechanisms of insulin? (basically just list them all actually)
A
- Stimulates glycogen synthase, inhibits glycogen phosphorylase
- Increases AA uptake and therefore protein synthesis, inhibits proteolysis
- Increases TAG synthesis in fat & liver, inhibits lipolysis
- Inhibits gluconeogenesis
- Promotes K ion entry into cells by stimulating Na/K ATPase. important clinically
23
Q
What is the approximate half life of insulin?
What happens once insulin action is complete?
A
- 5 minutes
- Insulin bound receptors are internalized by endocytosis and destroyed by insulin protease (some recycled)
24
Q
List the stimuli that promote insulin secretion
A
- Increased blood glucose
- Increased [AA] in plasma
- Glucagon (insulin is required to uptake glucose synthesized by gluconeogenesis)
- Other hormones controlling GI secretion (gastrin / secretin / CCK / GLP-1 / GIP)
- Vagal tone
25
List the stimuli that inhibit insulin secretion
- Low blood glucose
- Somatostatin (GHIH)
- Sympathetic (alpha 2) effects
- Stress (eg. hypoxia)
26
Why is insulin response to IV glucose less than it is to orally consumed glucose?
- Because orally consuming glucose causes vagal stimulation of insulin release as well as the effect of raised blood glucose on insulin release
- Vagus also stimulates release of other GI hormones that can also stimulate insulin release
27
What is the main function of glucagon? What is its main target?
- Raise blood glucose concentration
| - Acts mainly on the liver
28
Plasma half life of glucagon? Where is it degraded?
- 5-10mins plasma half life
| - Mainly degraded by liver
29
What hormones are involved in the glucose counter-regulatory control system?
- Insulin
- Glucagon
- Epinephrine
- GH
- cortisol
30
What type of receptor does glucagon act on?
- G Protein Coupled Receptor linked to the adenylate cyclase / cAMP system
31
What processes are initiated in liver cells when glycogen is bound?
- Increased glycogenolysis
- Increased gluconeogenesis (substrates: AA's and glycerol - from lipolysis)
- Formation of ketones from Fatty Acids (lipolysis)
32
What effect do amino acids have on the secretion of insulin and glucagon?
Why is this?
- AA's stimulate both insulin and glucagon release
- Adaptation to maintain blood glucose in carnivores. If you eat a high protein, low carb meal and only insulin was released then blood glucose would drop very low. Since glucagon is also released blood glucose is maintained so there I available energy for the brain and other tissues
33
List the stimuli that promote glucagon release
- Low blood glucose
- AA's in plasma
- Sympathetic innervation and epinephrine
- Cortisol
- Stress / exercise / infection
34
List the stimuli that inhibit glucagon release
- High blood glucose
- Free Fatty Acids and Ketones
- Insulin
- Somatostatin
35
Effect of parasympathetic innervation on insulin and glucagon release? What nerve is this via?
- Vagus
- Increases insulin secretion
- Increases glucagon secretion to a lesser extent, in association with the anticipatory phase of digestion
36
Effect of sympathetic innervation on insulin and glucagon release?
- Increases glucagon and epinephrine secretion
- Inhibits insulin
Want mobilization of glucose for fight or flight response
37
Where is somatostatin secreted from? What is its main pancreatic action??
- D-cells of the pancreas and the hypothalamus (aka GHIH)
| - Main pancreatic action is to slow GI absorption of nutrients to prevent spikes in plasma concentrations
38
Actions of somatostatin?
- Inhibit insulin and glucagon release in a paracrine fashion
- Inhibit GI tract activity
- Inhibit secretion of GH from anterior pituitary
39
What promotes the release of somatostatin?
- Elevated plasma AA's
| - Elevated blood glucose
40
What is the effect of exercise on blood glucose and why?
- Exercise causes insulin independent recruitment of GLUT-4 transporters to the cell surfaces of skeletal muscle. It also increases insulin sensitivity of these cells
- Effects last for hours, and regular exercise can cause prolonged increases in insulin sensitivity
- Therefore would cause blood glucose to decrease
41
What happens when starvation is entered and glucagon stores are depleted?
- Adipose tissue broken down into Free Fatty Acids
- FFA's can be used by most of the body for energy
- Liver converts FFA's to ketone bodies that the brain can use in periods of starvation
42
When fat stores are depleted in starvation what is the last energy store to be used?
- Protein
- When adipose is used up protein can be broken down to provide substrates for gluconeogenesis
- Breaking down bodies own protein is very weakening, makes you vulnerable to infection
43
What is type 1 diabetes also known as?
| Describe the pathophysiology of type 1 diabetes mellitus
- Insulin Dependent Diabetes Mellitus (IDDM)
- Autoimmune destruction of pancreatic beta cells results in inability to produce insulin. Results in starvation, ketoacidosis and death if untreated
44
Treatment of type 1 diabetes?
- Injected insulin
Peptide hormones can't be taken orally
45
Describe how ketoacidosis occurs in diabetes. How does this lead to death?
- Diabetes means can't access nutrients being consumed, so body goes into starvation and begins to produce ketone bodies as a energy source for the brain
- Lack of insulin causes depression of ketone body uptake, results in buildup of ketone bodies in plasma
- ketones are acidic and cause pH < 7.1 in the plasma, which is fatal within hours if untreated
46
What is type 2 diabetes also known as?
| Describe the pathophysiology of type 2 diabetes mellitus
- Non-Insulin Dependent Diabetes Mellitus (NIDDM)
- Peripheral tissues become insensitive to insulin (insulin resistance), due to either abnormal receptor response or reduction in receptor number
- Beta cells remain in-tact and there may even be hyperinsulinaemia
47
Causes / risk factors for type 2 diabetes? When does it usually present?
- Obesity, high sugar and animal fat diets with low exercise are risk factors
- Usually presents at >40yrs, but age of onset decreasing
48
Why is blood glucose raised in type 1 and type 2 diabetes?
- Type 1: inadequate insulin production
| - Type 2: inadequate tissue response
49
How does a glucose tolerance test work? What does it diagnose?
1. Fasting blood glucose measured
2. Patient consumes some glucose
3. Glucose should be back to fasting baseline after an hour, if after 2 hours still elevated indicates diabetes
- Diagnoses diabetes, doesn't distinguish between type 1 and 2
50
How to convert mg/dl (US units) to mM?
Divide by 18
MW of glucose is 180 and mM is per litre
51
What is the effect of diabetes on blood glucose? Possible complications due to this?
- Hyperglycaemia
Leads to:
- Retinopathy
- Neuropathy
- Nephropathy
- CVS disease
