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Metabolic Endocrinology > Gut Hormones > Flashcards

Gut Hormones Flashcards

1
Q

What is central to many metabolic pathways?

A

Glucose

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2
Q

Which cells/organs are dependent on glucose?

A

Neurons, RBC and the brain

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3
Q

What is used as an energy source in a starvation state?

A

Fat will be converted to ketones by lipolysis as an alternative energy source to glucose

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4
Q

Between meals where is blood glucose from?

A

Hepatic glycogen

Depending on the frequency of snacking, glycogenolysis and gluconeogenesis may be more or less active

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5
Q

When is gluconeogenesis the main source of blood glucose?

A

Late at night or early in the morning (fasting state)

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6
Q

How are glucose levels maintained?

A

Glucose levels are regulated by hormones that affect appetite and cell metabolism

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7
Q

Which are the major hormones that control blood glucose?

A

Insulin and glucagon are the first responses to glucose

Insulin is the only hormone which acts to lower blood glucose

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8
Q

What are some other hormones that help regulate blood glucose?

A

Epinephrine, cortisol, GH, thyroid hormone, secretin, cholecytokinin
All of these hormones (including glucagon) act at the same time and form an integrated control system)

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9
Q

Which receptors are glucagon and epinephrine linked to?

A

Linked to G-proteins

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10
Q

Which receptor is insulin bind to?

A

Receptors with intrinsic tyrosine kinase activity

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11
Q

How is enzyme activity regulated?

A

Through phosphorylation (posphokinases) and dephosphorylation (phosphatases), switching between active and inactive state, activation cascade

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12
Q

What is the fucntion of GI tract hormones?

A

To regulate activity of the stomach, intestine and pancreas (in addition to the regulation of blood glucose)

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13
Q

Where else can GI hormones be found?

A

Central or peripheral nervous system

- somatostatin, gastrin, CCK, vasointestinal peptide, insulin ,calcitonin)

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14
Q

Where are the GI hormones produced?

A

Produced in the cell body of neurons

They may modulate signal transmission

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15
Q

What is the most common endocrine disorder?

A

Diabetes mellitus

- symptoms: loss of weight, polydipsea, polyuria, polyphagia

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16
Q

What did Minkowski discover?

A

The abnormalities of the islets of Langerhans

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17
Q

What did Banting and Best do?

A

They isolated insulin and show that it lowers blood glucose in dogs

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18
Q

How much do islets of Langerhans weigh?

A

1 -2 g

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19
Q

What does the exocrine pancreas secrete? and where do they secrete enzymes to?

A

They secrete a digestive juice composed of digestive enzymes secreted by the acinar cells and aqueous NaHCO3 secreted by the duct cells

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20
Q

What does the endocrine pancrease secrete?

A

Insulin and glucagon into the blood

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21
Q

What do acinar cells secrete?

A

Digestive enzymes: proteases, amylase, lipase

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22
Q

What do duct cells secrete?

A

NaHCO3

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23
Q

What cells do the Islet of Langerhans have?

A
  • a-cells: glucagon
  • b-cells: insulin
  • d-cells: somatostatin
  • f-cells: pancreatic polypeptide
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24
Q

Are islet cells vascularized?

A

islets are highly vascularized - 5 to 10x blood flow of exocrine pancreas

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25
Where are the blood supplies centrally located?
In the b-cells, insulin detects glucose levels then blood travels to more peripheral A and D cells
26
What is glucagon also produced as?
Preproglucagon processed to proglucagon to glucagon
27
How does the body response to an increase in blood glucose?
- a-cells will decrease glucagon - b-cells will increase insulin - both processed will decrease blood glucose levels to normal
28
What is the vagus nerve?
Longest nerve in the body | acts as a sensory neuron and a motor neuron
29
What is the function of the vagus nerve?
Main neuronal coordinator of appetite control, digestion and metabolism Release of acetylcholine in the pancreas stimulates insulin release
30
What does an increase in blood glucose concentration trigger?
- Islet b-cells will trigger an release of insulin to lower blood glucose, blood FA, blood AA - increase in protein synthesis and fuel storage - increase in GI hormones from food intake - parasympathetic stimulation of islet b cells
31
How is insulin released from B cells?
- Uptake of glucose by GLUT 2 - Aerobic glycolysis and increase of ATP/ADP ratio - Inhibition of K-ATP channels, reduction of K efflux, membrane depolarization - Opening of Ca2+ channels: exocytosis of insulin containing granules - Opening of Ca2+ activated K channels (repolarization of the membrane)
32
What does GLP-1 stimulate?
GLP-1 binds to receptors and trigger cAMP production. It potentiates the amplification pathway, ion channels and exocytosis
33
What is the fasting glucose level?
3 -5 mmol/L
34
What are the anabolic effects of insulin?
- protein synthesis - lipid and glycogen synthesis - inhibition of their degradation
35
Where are the key target cells of insulin?
Liver, muscle, adipose tissue
36
What does insulin promote?
Insulin is essential for normal growth and development, insulin promotes cell growth
37
What does glucagon increase?
Glucagon increases many catabolic processes particularly in the liver - production of glucose
38
Why is insulin always secreted?
Insulin is continuosly secreted to enable peripheral tissues to uptake glucose
39
What does glucose suppress?
Glucose suppresses GH secretion - and increases lipolysis
40
Where are the major sites of expression of GLUT 2?
B cells of islets, liver, epithelial cells of small intestine, kidneys
41
What is the function of GLUT2?
B cell glucose sensor, transport out of intestinal and renal epithelial cells
42
What is the function of GLUT 4?
Insulin-stimulated glucose uptake
43
What are the major sites of expression of GLUT4?
Skeletal and cardiac muscle, adipose tissue, other tissues
44
How does insulin stimulate the uptake of glucose?
By stimulating glucokinase and promote phosphorylation of glucose to form glucose-6-phosphate. The conc gradient of glucose is needed for faciliated uptake via GLU2
45
Can insulin bind to other receptors?
Insulin can bind to insulin receptors, IGF-1 and IGF-II receptors
46
What does of insulin trigger?
Activation of the insulin receptor causes activation of phosphoinositide 3 kinase, which speeds the translocation of the GLUT 4 containing endosomes into the cell membrane.
47
How many membrane domain does GLUT 4 span through?
12 membrane spanning domains
48
How is glucagon signaling initiated?
- glucagon binds to a G coupled protein receptor which results in a change in conformation of the receptor - allow GTP/GDP exchange - the free alpha subunit actiates adenylate cyclase - cAMP binds regulatory subunitsto increase PKA - increases glycogenolysis and gluconeogenesis - decrease glycogenesis and glycolysis
49
What is the influence of insulin and glucagon on glucose metabolism?
Insulin: increases triacylglycerol synthesis Glucagon: increase FA mobilization
50
What are the endocrine effects of insulin on the liver?
- reversal of catabolic features of insulin deficiency - inhibits glycogenolysis - inhibits conversion of FA and AA to keto acids - promotes glucose storage as glycogen
51
What are the endocrine effects of insulin on muscles?
- increased protein synthesis - increased AA transport - increases ribosomal protein synthesis - increases glucose transport - induces glycogen synthetase and inhibits phosphorylase
52
What are the endocrine effects of insulin on adipose tissue?
- increases TG storage - glucose tranport into cell provides glycerol phosphate to permit esterification of FA supplied by lipoprotein transport
53
What effect does GLP-1 have on the brain?
inhibits appetite
54
What does glucagon affect in the islet cells and liver?
Islet: stimulates insulin secretion Liver: stimulates glucogenolysis, glucogenesis, FA oxidation and ketogenesis inhibits glucogen synthesis and FA synthesis
55
What are the effects of insulin on ion transport?
insulin increases K intake into cells - possible mechanis: activation of the Na/K pump - glucose and insulin relieve hyperkalemia Changes in Ca flux - increase of Ca in mitochondria
56
What are the four most common weight loss surgery procedures?
- adjustable gastric band - roux-en-Y gastric bypass - duodenal switch - vertical sleeve gastrectomy
57
What is somatostatin?
An inhibitor of many hormones - pituatary: negative release of GH release - peripheral and CNS: neuromodulatory effects - GI tract: inhibitor of the release of many GI hormones - pancrease: inhibitor of insulin and glucagon secretion
58
What is the function of pancreatic polypeptide?
- reduces appetite - inhibits the secretion of digestive enzymes of the pancreas - blocks contraction of the gall bladder: inhibitor of bile secretion
59
What regulates pancreatic polypeptide?
It may increase by vagus nerve and CCK in response to a meal not dependent on glucose levels
60
When does pancreatic polypeptide increase/
increases after meals and remains high for several hours
61
Which hormones does the stomach release?
- ghrelin: stimulates hunger and GH release | - gastrin: acid secretion
62
Which hormones does the pancrease secrete?
- insulin and glucagon: glucose homeostasis - pancreatic polypeptide: gastric motility and satiation - amylin: glucose homeostasis and gastric motility
63
What is ghrelin important for?
ghrelin is an important meal initiation signal
64
What is prader-willi syndrome caused by?
excessive ghrelin secretion - cannot stop eating and do not feel satiated
65
Where are GLP-1 made?
In L cells in the ileum and colon
66
How long is the half life of GLP-1?
90 seconds
67
What is an incretin?
GLP-1 is an incretin - stimulates insulin secretion - absorbs glucose in circulation - incretins enhance glucose dependent insulin secretion

Metabolic Endocrinology (4 decks)

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