Glucose Homeostasis Flashcards
(113 cards)
1
Q
What are the purposes of glucose homeostasis?
A
Controls glucose metabolism
Maintains normal blood glucose levels in the body
2
Q
What does severe HYPOglycemia cause? Why?
A
Can lead to coma and death, because glucose is the main source of energy for the brain
3
Q
What does chronic HYPERglycemia lead to?
A
Endothelial dysfunction and DM
4
Q
What are the sources of glucose in the body? (3)
A
- Intestinal Absorption
- Glycogen Breakdown
- Gluconeogenesis
5
Q
What is intestinal absorption of glucose?
A
Derived from dietary carbohydrates consumed through food
6
Q
What is glycogen breakdown that is a source of glucose?
A
Occurs in the liver, which stores between 25 to 138g of glycogen
7
Q
How long does the glycogen in the liver provide an energy source for?
A
Lasts approximately 3 to 8 hours
8
Q
What is gluconeogensis?
A
The synthesis of glucose from non-carbohydrate precursors
9
Q
What are the key substrates of gluconeogensis?
A
Lactate and pyruvate
Amino acids such as alanine and glutamine
10
Q
What % of carbohydrates does our body turn into glucose?
A
100% of the carbohydrates we eat
It affects our blood sugar levels quickly, within an hour or two after
11
Q
What % of protein consumed is broken down into glucose?
A
58%
12
Q
What % of fat consumed is broken down into glucose?
A
10%
13
Q
What is the normal range of fasting state glucose?
A
60 to 100mg/dl
14
Q
What is the normal range of postprandial glucose?
A
100 to 160mg/dl
15
Q
Why is maintaining the blood glucose levels within normal range very important?
A
- Nervous tissues use glucose as a major energy substrate (especially the brain)
- The brain requires glucose during prolonged fasting
- Mature RBCs do not contain mitochondria, thus energy is obtained via ANAEROBIC GLYCOLYSIS
- During heavy exercise, skeletal muscle utilizes glycogen and blood glucose for energy production
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16
Q
What are the control systems of glucose? (5)
A
- Glucose transportes (GLUT 1 to1 4)
- Controlling hormones (Insulin, Glucagon, Cortisol, Epinephrine)
- Insulin signaling sequence (Glucagon sequencing)
- Effector cells (Muscle, liver, and adipose tissue)
- Feedback loops (Positive and negative feedback)
17
Q
What is the purpose of the glucose control systems?
A
To control the range of glycose within normal limits
18
Q
How many Islet cells are there in the endocrine pancreas?
A
1 million Islets, 1 to 2% of pancreas mass
19
Q
What are the different types of cells of the pancreas?
A
Alpha (15 to 20%)
Beta (65 to 80%)
Delta
F
20
Q
What do beta cells produce?
A
Insulin
21
Q
What do alpha cells produce?
A
Glucagon
22
Q
What do delta cells produce?
A
Somatostatin
23
Q
What do F cells produce?
A
Pancreatic polypeptide
24
Q
What is insulin?
A
A protein hormone consisting of two amino acid chains linked by disulfide bonds
25
What are the components of insulin?
A chain (21 amino acids)
B chain (30 amino acids)
3 disulfide binds
26
What is the half-life of insulin and why?
5 minutes, because of its fast-acting effect, it cannot be circulating in the blood for long as it will lead to HYPOglycemia
27
What are factors affecting the release of insulin?
The main stimulus is glucose, amino acids also influence its release because they convert to glucose
28
What are the main glucose transporters?
GLUT1
GLUT2
GLUT3
GLUT4
GLUT5
29
Where is GLUT1 found?
Blood
BBB
Heart
30
Is GLUT1 insulin-dependent or independent?
Insulin independent
31
Where is GLUT2 found?
Liver
Pancreas
Small Intestine
32
What are the characteristics of GLUT2?
Insulin-Independent
High bioavailability
Low affinity
33
Where is GLUT3 found?
Brain
Neurons
Sperm
34
What are the characteristics of GLUT3?
Insulin Independent
Low bioavailability
High affinity
35
What does high affinity mean?
That it can sense and bind glucose even when the concentrations are really low
36
Where is GLUT4 found?
Skeletal Muscle
Adipose Tissue
Heart
37
Is GLUT4 insulin-dependent or insulin - independent?
Insulin-dependent (insulin-sensitive)
38
What does high bioavailability mean?
A high bioavailability means that a greater concentration of substrate is required in order to reach 1/2 of the maximum rate
39
What is the process of insulin secretion when there is a decrease of glucose in the blood?
Decreased glucose in blood, which slows down the metabolism, which lowers the levels of ATP, and because the K+ channels are ATP sensitive, they would open and let K+ out --> the leakage of K+ makes the cell more negative.
The cell is at resting membrane potential, the voltage-gated Ca2+ channels close, calcium does not enter the cell and there is no insulin secretion.
Insulin remains in secretory vesicles
40
What is the process of insulin secretion where there is an increase of glucose in the blood?
An increase in glucose in the blood leads to increased glycolysis and citric acid cycle --> Increase in ATP, which causes the K+ channels to close, K+ does not leave the cell, and the cell remains positive (depolarizes), calcium channels open and allow for calcium to come into the cell. Ca2+ entry triggers exocytosis and insulin is secreted.
41
What is the insulin secretion process like? Why?
Biphasic, the first phase uses the already synthesized insulin whilst the second one produces newly synthesized insulin
42
When is there no insulin being produced?
When plasma glucose is below 50mg/dl
43
When does the half-maximal insulin response occur?
At 150mg/dl
44
When does the maximum isnulin response occur?
At 300mg/dl
45
What is the isnulin secretion process like?
Upon glucose stimulation - an initial burst of secretion
Then, a second phase of gradual increment that lasts as long as blood glucose is high
46
What is the main regulator of insulin secretion?
Stimulator: increase in serum glucose
Inhibitor: decrease in glucose
47
What is the purpose of insulin signaling?
To activate the uptake of insulin
48
What is the Insulin receptor?
A tyrosine kinase consists of 2 units
49
What happens to the insulin receptor when bound to insulin?
It dimerizes
50
What happens inside the cell when an insulin receptor binds to insulin?
Autophosphorylation occurs, increasing the tyrosine kinase activity
51
What is the GLUT4 like when insulin levels are low?
They are present in cytoplasmic vesicles, swimming in the cytoplasm, where they are useless fir transporting glucose
52
What happens to the GLUT4 when there is binding of insulin to insulin receptors?
Rapid fusion of the cytoplasmic vesicle with the membrane and insertion of glucose transporter and take up the glucose
53
What are the effects of the insulin signal pathway?
Effects on lipid metabolism
Effects on growth
Effects on protein metabolism
54
What are the metabolic effects of insulin on the liver?
Stimulates glucose oxidation
Promotes glucose storage as glycogen
Decreases the production of glucose: inhibits glycogenolysis and gluconeogenesis
55
What are the metabolic effects of insulin on the muscle?
Stimulates glucose uptake (GLUT4)
Promotes glucose storage as glycogen
56
What are the metabolic effects of insulin on the adipose tissue?
Stimulates glucose transport into adipocytes
Promotes the conversion of glucose into triglycerides and fatty acids
57
What is the effect of glycogen phosphorylase b?
Removes phosphate and activates glycogen phosphorylase a, which then leads to glycogen degradation
58
What is the effect of protein phosphatase 1?
Removes the phosphate group off of glycogen synthase b into glycogen synthase a and cause glycogen synthesis
59
What is the definition of Brain-Islet Axis?
Refers to the communication pathways between the CNS and pancreatic islets
60
What is the function of the Brain-Islet Axis?
It helps regulate insulin secretion and overall glucose homeostasis
61
What are the innervations of the pancreas?
Both parasympathetic and sympathetic nerve fibers
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63
What is the mechanism of Brain-Islet Axis?
Vagal Nerve stimulation: parasympathetic signals through the vagus nerve play a crucial role in stimulating insulin secretion, especially in response to food intake.
Sympathetic regulation: the sympathetic nervous system can inhibit insulin secretion during stress or hypoglycemia to prioritize glucose supply for essential organs like the brain.
64
What is the role of ventromedial hypothalamus?
Significant role in regulating glucose metabolism and energy homeostasis. It acts as an inhibitory control center over the endocrine function of pancreatic beta cells
65
What is the result of destruction or dysfunction of the VMH?
Can lead to hyper-secretion of insulin secretion
66
What are the roles of the VMH?
Inhibitory Influence
Energy Balance Regulation
67
What is the inhibitory influence of the VMH?
The VMH exerts an inhibitory effect on pancreatic beta-cells, helping to regulate insulin secretion and prevent excessive insulin release
68
What is the Energy Balance Regulation effect of VMH?
The VMH integrates neural and hormonal signals related to feeding, energy expenditure, and glucose metabolism
69
What are the clinical implications of destruction of the VMH?
Hyperinsulinemia: persistent insulin hypersecretion --> may increase the risk of developing insulin resistance over time
Energy Storage & Weight Gain: excessive insulin promotes glucose uptake and storage
70
What is the liver-islet axis?
The liver has a key role in glucose homeostasis by storing or releasing glucose
71
What is the storing of glucose known as?
Glycogenesis
72
What is the process of releasing glucose known as?
Glycogenolysis or gluconeogenesis
73
What is the role of the liver-islet axis?
Vital bidirectional communication pathway between the liver and pancreatic islets is essential for maintaining glucose homeostasis and regulating insulin secretion.
74
What are the key functions of the liver-islet axis?
1. Glucose sensing and insulin regulation
2. Insulin clearance
75
What is the glucose sensing and insulin regulation function of the liver-islet axis?
When the blood glucose levels rise, the liver metabolizes glucose and releases signals to promote insulin secretion from the pancreatic islets.
Metabolites produced by the delivery of hormones, such as glucagon-like peptides can modulate insulin secretion and sensitivity.
76
When do blood glucose levels rise?
After a meal for instance
77
What is the insulin clearance function of the liver-islet axis?
The liver is responsible for clearing a significant portion of insulin from the bloodstream. This action helps maintain appropriate insulin levels and prevents prolonged hyperinsulinemia
78
What is the gut-islet axis?
The gut releases various hormones upon nutrient ingestion, including GLP-1 and GIP, that bind to their receptors on pancreatic beta cells to initiate insulin secretion
79
What is the role of the gut-islet axis?
The axis is essential for coordinating digestive and metabolic responses
80
What is the role of GLP-1?
Stimulates insulin gene expression, induces suppression of endogenous glucose glucose production
81
What is the role of GIP?
Mediate insulin secretion
82
When are Limostatin and Neuromedin U secreted and what is their function?
Secreted during fasting and their action is to suppress insulin release
83
When are GLP-1 and GIP released?
In response to food intake and enhance insulin release
84
What are the MOA of GLP-1?
Stimulates insulin gene expression
Suppression of glucose production
Slows gastric emptying, contributes to a gradual rise in blood glucose, promoting efficient insulin response
85
What is the MOA of GIP?
Mediates insulin secretion, has a lesser impact n gastric emptying compared to GLP-1
86
What is the adipocytes/myocytes - islet axis?
Adipocytes and myokines secreted from the adipose and muscle tissue
87
What is Leptin?
The most famous adipokine mainly acts on its receptors in the hypothalamic arcuate nucleus to inhibit food intake.
88
What is leptin like in fat people?
There is increased leptin because of the fact that it is produced from adipocytes and they have more adipocytes compared to lean people but their receptors are insensitive to it
89
What are the interaction between leptin and insulin?
1. Leptin-induced insulin secretion due to the opening of K+ ATP channels, decrease in calcium, insulin remains in vessels
2. Leptin can also act directly on pancreatic beta cells, suppressing insulin gene expression, which helps prevent excessive insulin release
90
What is the function of glucagon?
Increases concentration of glucose
91
What is Glucagon?
A potent hyperglycemic agent
92
What is the half-life of glucagon?
4 to 6 minutes
93
What are the factors affecting glucagon release?
Blood amino acids, glucose
94
What is the glucose-dependent glucagon secretion like?
If low levels of glucose are detected, then the ATP is low, which leads to the ATP-sensitive K+ channels to close, Ca2+ enters, depolarization, and glucagon release through exocytosis
95
WHere is glucagon secreted from?
Alpha cells of the pancreas
96
What are the stimuli for glucagon secretion? (5)
1. Decreased blood glucose levels
2. Increased serum amino acids (arginine and alanine)
3. Sympathetic nervous system stimulation
4. Stress
5. Excercise
97
What are inhibitors of glucagon secretion? (3)
1. Somatostatin
2. Insulin
3. Increased blood glucose levels
98
What is diabetes mellitus?
A serious disorder of carbohydrate metabolism, which results from hypo-secretion or hypoactivity of insulin
99
What are the three cardinal signs of DM?
1. Polyuria
2. Polydipsia
3. Polyphagia
100
What is type 1 diabetes?
Characterized by an autoimmune attack on the beta cells of the pancreas, leading to decreased or no insulin production
101
What is the main population that type 1 diabetes affects?
It typically has a younger onset and often affects individuals who are thin
102
What are people with type 1 diabetes prone to?
Prone to ketosis, a condition where ketone bodies are produced due to fat breakdown
103
What is type 2 diabetes?
Results from a combination of insulin resistance and insulin deficiency, the most common type (90%)
104
Is type 2 diabetes usually familial or sporadic?
Familial (genetic link)
105
What is the population that type 2 diabetes usually affects?
Older onset and is commonly associated with obesity
106
What are examples of hyperglycemic hormones? (6)
1. Growth hormone
2. ACTH
3. TSH
4. Epinephrine or adrenaline
5. Glucocorticoids
6. Thyroxine
107
Why are there so many HYPERglycemic hormones?
Due to how dangerous HYPOglycemia is
108
What is the only HYPOglycemic hormone?
Insulin
109
110
What is the effect of thyroxine as a hyperglycemic hormone?
1. Increases the rate of absorption of glucose from the intestines
2. Stimulating gluconeogenesis and glycogenolysis
3. Inhibit glycogenesis
111
What is the effect of epinephrine as a hyperglycemic hormone? (5)
1. Causes glycogen breakdown, stimulates gluconeogenesis, and promotes glucose release from the liver
2. Simulates glycolysis in muscle tissue
3. Promotes lipolysis in adipose tissue
4. Decreases insulin secretion
5. Increases glucagon secretion
112
What is the effect of cortisol as a hyperglycemic hormone? (3)
1. Stimulates gluconeogenesis in the liver and promotes the formation of glycogen in the liver
2. Reduces glucose uptake into muscle and adipose tissue
3. Promotes protein and lipid breakdown into products that can be used for gluconeogenesis
113
