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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
Q

Where are the blood supplies centrally located?

A

In the b-cells, insulin detects glucose levels then blood travels to more peripheral A and D cells

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26
Q

What is glucagon also produced as?

A

Preproglucagon processed to proglucagon to glucagon

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27
Q

How does the body response to an increase in blood glucose?

A
  • a-cells will decrease glucagon
  • b-cells will increase insulin
  • both processed will decrease blood glucose levels to normal
28
Q

What is the vagus nerve?

A

Longest nerve in the body

acts as a sensory neuron and a motor neuron

29
Q

What is the function of the vagus nerve?

A

Main neuronal coordinator of appetite control, digestion and metabolism
Release of acetylcholine in the pancreas stimulates insulin release

30
Q

What does an increase in blood glucose concentration trigger?

A
  • 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
Q

How is insulin released from B cells?

A
  • 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
Q

What does GLP-1 stimulate?

A

GLP-1 binds to receptors and trigger cAMP production. It potentiates the amplification pathway, ion channels and exocytosis

33
Q

What is the fasting glucose level?

A

3 -5 mmol/L

34
Q

What are the anabolic effects of insulin?

A
  • protein synthesis
  • lipid and glycogen synthesis
  • inhibition of their degradation
35
Q

Where are the key target cells of insulin?

A

Liver, muscle, adipose tissue

36
Q

What does insulin promote?

A

Insulin is essential for normal growth and development, insulin promotes cell growth

37
Q

What does glucagon increase?

A

Glucagon increases many catabolic processes particularly in the liver - production of glucose

38
Q

Why is insulin always secreted?

A

Insulin is continuosly secreted to enable peripheral tissues to uptake glucose

39
Q

What does glucose suppress?

A

Glucose suppresses GH secretion - and increases lipolysis

40
Q

Where are the major sites of expression of GLUT 2?

A

B cells of islets, liver, epithelial cells of small intestine, kidneys

41
Q

What is the function of GLUT2?

A

B cell glucose sensor, transport out of intestinal and renal epithelial cells

42
Q

What is the function of GLUT 4?

A

Insulin-stimulated glucose uptake

43
Q

What are the major sites of expression of GLUT4?

A

Skeletal and cardiac muscle, adipose tissue, other tissues

44
Q

How does insulin stimulate the uptake of glucose?

A

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
Q

Can insulin bind to other receptors?

A

Insulin can bind to insulin receptors, IGF-1 and IGF-II receptors

46
Q

What does of insulin trigger?

A

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
Q

How many membrane domain does GLUT 4 span through?

A

12 membrane spanning domains

48
Q

How is glucagon signaling initiated?

A
  • 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
Q

What is the influence of insulin and glucagon on glucose metabolism?

A

Insulin: increases triacylglycerol synthesis
Glucagon: increase FA mobilization

50
Q

What are the endocrine effects of insulin on the liver?

A
  • reversal of catabolic features of insulin deficiency
  • inhibits glycogenolysis
  • inhibits conversion of FA and AA to keto acids
  • promotes glucose storage as glycogen
51
Q

What are the endocrine effects of insulin on muscles?

A
  • increased protein synthesis
  • increased AA transport
  • increases ribosomal protein synthesis
  • increases glucose transport
  • induces glycogen synthetase and inhibits phosphorylase
52
Q

What are the endocrine effects of insulin on adipose tissue?

A
  • increases TG storage
  • glucose tranport into cell provides glycerol phosphate to permit esterification of FA supplied by lipoprotein transport
53
Q

What effect does GLP-1 have on the brain?

A

inhibits appetite

54
Q

What does glucagon affect in the islet cells and liver?

A

Islet: stimulates insulin secretion
Liver: stimulates glucogenolysis, glucogenesis, FA oxidation and ketogenesis
inhibits glucogen synthesis and FA synthesis

55
Q

What are the effects of insulin on ion transport?

A

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
Q

What are the four most common weight loss surgery procedures?

A
  • adjustable gastric band
  • roux-en-Y gastric bypass
  • duodenal switch
  • vertical sleeve gastrectomy
57
Q

What is somatostatin?

A

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
Q

What is the function of pancreatic polypeptide?

A
  • reduces appetite
  • inhibits the secretion of digestive enzymes of the pancreas
  • blocks contraction of the gall bladder: inhibitor of bile secretion
59
Q

What regulates pancreatic polypeptide?

A

It may increase by vagus nerve and CCK in response to a meal
not dependent on glucose levels

60
Q

When does pancreatic polypeptide increase/

A

increases after meals and remains high for several hours

61
Q

Which hormones does the stomach release?

A
  • ghrelin: stimulates hunger and GH release

- gastrin: acid secretion

62
Q

Which hormones does the pancrease secrete?

A
  • insulin and glucagon: glucose homeostasis
  • pancreatic polypeptide: gastric motility and satiation
  • amylin: glucose homeostasis and gastric motility
63
Q

What is ghrelin important for?

A

ghrelin is an important meal initiation signal

64
Q

What is prader-willi syndrome caused by?

A

excessive ghrelin secretion - cannot stop eating and do not feel satiated

65
Q

Where are GLP-1 made?

A

In L cells in the ileum and colon

66
Q

How long is the half life of GLP-1?

A

90 seconds

67
Q

What is an incretin?

A

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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