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SUGER > Endocrine Pancreas > Flashcards

Endocrine Pancreas Flashcards

1
Q

What forms the pancreas

A

At junction of foregut and midgut 2 pancreatic buds (dorsal and ventral) are generated and eventually fuse to form the pancreas

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2
Q

When does the exocrine function of the pancreas start

A

After birth

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3
Q

When does endocrine function begin

A

10-15 weeks

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4
Q

Location of pancreas

A

Retroperitoneal
Posterior to greater curvature of stomach

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5
Q

Length of pancreas

A

12-15cm

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6
Q

Where does the head of the pancreas sit

A

Near C-portion of duodenum

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7
Q

Acini

A

98-99% of cells are clusters

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8
Q

Which cells form exocrine activity

A

Acinar cells

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9
Q

Which cells perform endocrine activity

A

Islet cells

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10
Q

Exocrine activity

A

Manufacture and secrete fluid and digestive enzymes (pancreatic juice) which is released into the gut

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11
Q

Endocrine activity

A

Manufacture and release several peptide hormones into portal vein

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12
Q

What is the site of insulin and glucagon secretion

A

Islet of Langerhan’s

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13
Q

Alpha cells

A

Secrete glucagon

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14
Q

Beta cells

A

Secrete insulin

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15
Q

Percentage total volume of pancreas that is made up of islets of langerhans

A

2-3%

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16
Q

Delta cells

A

Secrete somatostatin

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17
Q

Paracrine crosstalk

A

Between Alpha and beta cells is physiological
I.e. local insulin release inhibits glucagon

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18
Q

How many amino acids make up insulin

A

51

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19
Q

Functions of insulin

A

Reduces glucose output by liver
Increases storage of glucose, fatty acids and amino acids

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20
Q

How many amino acids form glucagon

A

29

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21
Q

Function of glucagon

A

Mobilises glucose, fatty acids and amino acids from stores

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22
Q

What hormone stimulates the release of glucagon

A

Ghrelin

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23
Q

What hormone inhibits gastric emptying

A

Pancreatic polypeptide

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24
Q

Function of somatostatin

A

Inhibitor

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25
Q

Counterregulatory hormes of insulin

A

Glucagon
Adrenaline
Cortisol
Growth hormone

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26
Q

What does insulin suppress

A

Hepatic glucose output
Decrease Glycogenolysis and gluconeogenesis
Lipolysis
Breakdown of muscle (decreased ketogenesis)

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27
Q

What does insulin increase

A

Glucose uptake by insulin sensitive tissue
Muscles- glycogen and protein synthesis
Fat- fatty acid synthesis

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28
Q

Glucagon increases

A

Hepatic glucose output- increases Glycogenolysis and gluconeogenesis
Stimulates peripheral release of gluconeogenic precursors (glycerol and amino acids)
-lipolysis
-muscle Glycogenolysis and breakdown

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29
Q

Glucagon reduces

A

Peripheral glucose uptake

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30
Q

Which hormone increase Glycogenolysis and gluconeogenesis

A

Glucagon

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31
Q

Which hormone decrease Glycogenolysis and gluconeogenesis

A

Insulin

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32
Q

Insulin secretion by the beta cell

A

Glucose enters by GLUT2 glucose transporter
Glucose is phosphorylated by glucokinase —> glucose-6-phosphate
Glucose metabolism —> increase ATP present
Closes K+ channel —> depolarises membrane
Voltage gated Ca2+ channels opens and Ca2+ influx
Mobilisation of insulin secretory granules and release of insulin by exocytosis

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33
Q

GLUT2

A

Low affinity transporter

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34
Q

Proinsulin

A

contains the A and B chains of insulin (21 and 30 amino acid residues respectively), joined by the C peptide.
Disulfide bridges link a and B chains
Presence of C peptide implies endogenous insulin production

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35
Q

What form is insulin secreted in

A

Proinsulin

36
Q

What type of bond links A and B insulin chains

A

Disulphide bridges

37
Q

Proinsulin is composed of

A

Insulin and C-peptide

38
Q

What does presence of C peptide imply

A

Endogenous insulin production

39
Q

Biphasic insulin release

A

B-cells sense rising glucose and aim to metabolise it
1st. Rapid release of stored product
2. Response is slower and it is the release of newly synthesised hormone

40
Q

Insulin action in muscle and fat cells

A

Insulin receptor
Intracellular signaling cascades
Intracellular GLUT4 vesicles
GLUT4 vesicle mobilisation to plasma membrane and integration into membrane
Glucose entry into cells via GLUT4

41
Q

What organ is a short-term glucose buffer

A

Liver

42
Q

Normal blood glucose

A

5 mmol/mol

43
Q

Blood glucose is too high

A

> 6 mmol/mol

44
Q

Short term response to high glucose

A

Glycogenesis

45
Q

Long term response to high blood glucose

A

Lipogenesis

46
Q

Low blood glucose

A

<4 mmol/mol

47
Q

Short term response to low blood glucose

A

Glycogenolysis

48
Q

Long term response to low blood glucose

A

Gluconeogenesis

49
Q

Where are primary glucose sensors

A

Pancreatic islets

50
Q

Glucose sensing- other than islets

A

Also in medulla, hypothalamus and carotid bodies
Inputs from eye, nose, taste buds, gut all involved in regulating food
Sensory cells in gut wall also stimulate insulin release from pancreas - incretins

51
Q

Incretins

A

Gut hormones stimulating insulin release are called incretins, glucagon-like peptide (GLP-1) and glucose-dependent insulinotrophic peptide(GIP)

52
Q

When is insulin response greater

A

Following oral glucose than intravenous glucose despite similar plasma glucose concentrations

53
Q

Mechanism of incretins

A

Increase insulin
Decrease glucagon
Delays gastric emptying

54
Q

GLP-1

A

Glucose dependent and short half life
Dipeptidyl peptidases IV cleaves GLP-1
Half-life of GLP-1 = 1-2 mins
DPP-IV prevents hypoglycaemia

55
Q

Half life of GLP-1

A

1-2 mins
- prevents hypoglycaemia

56
Q

In fasting state where does glucose come from

A

Liver-
Breakdown of glycogen
-gluconeogenesis

57
Q

What are the precursors for gluconeogenesis

A

Lactate
Alanine
Glycerol

58
Q

What do muscles use for fuel in fasting state

A

Free fatty acids

59
Q

Post prandial

A

After feeding

60
Q

What percentage of ingested glucose goes to liver

A

40%

61
Q

What percentage of ingested glucose goes to periphery (mostly muscle)

A

60%

62
Q

After feeding

A

physiological need to dispose of a nutrient load
Rising glucose (5-10 min after eating) stimulates 5-10 fold increase in insulin secretion and suppresses glucagon

63
Q

What is excess glucose converted into

A

Fats

64
Q

What does high insulin and glucose levels suppress

A

lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall

65
Q

What stimulates release of glucagon

A

Hypoglycaemia

66
Q

Action of glucagon on liver

A

Glycogenolysis
Gluconeogenesis from lactate and amino acids

67
Q

What inhibits release of glucagon

A

Hyperglycaemia

68
Q

What stimulates release of insulin

A

Hyperglycaemia

69
Q

Actions of insulin

A

Accelerate facilitated diffusion of glucose into cells
Speed conversion of glucose into glycogen
Increase uptake of amino acids and increase protein synthesis
Speed synthesis of fatty acids
Slow glycogenolysis
Slow gluconeogenesis

70
Q

What inhibits insulin release

A

Hypoglycaemia

71
Q

Diabetes mellitus

A

Disorder of carbohydrate metabolism characterised by hyperglycaemia

72
Q

Mechanism of diabetes mellitus type 2

A

Mutation in K+ (ATP activated) channels so remains open longer than it should —> need higher blood glucose in order for insulin secretion

73
Q

What can treat type 2 diabetes

A

Sulphonylureas
Synthetic incretins

74
Q

Synthetic incretins

A

Synthetic incretins
Stimulates insulin secretion which lowers blood glucose and decreases gastric emptying by acting as DDP-IV inhibitiors

75
Q

Action of sulphonylureas

A

Potassium channel closes and depolarises cell membranes

76
Q

Pathogenesis of diabetic ketoacidosis - no hepatic insulin effect

A

Unrestrained glucose and ketone production
- more glucose enters blood
- hyperglycaemia and raised plasma ketones
- glycosuria/ketonuria

77
Q

Pathogenesis of diabetic ketoacidosis- no muscle/fat insulin effect

A

Impaired glucose clearance and muscle/fat breakdown
- less glucose enters peripheral tissues
-hyperglycaemia and raised plasma ketones
- glycosuria/ketonuria

78
Q

Pathogenesis of diabetic ketoacidosis - absent insulin secretion

A

No hepatic insulin effect
No muscle/fat insulin effect

79
Q

A 13 year old boy is prescribed insulin as a treatment for his Type I diabetes mellitus. Which of the following metabolic processes is upregulated by insulin?

A

Expression of GLUT4 in muscle cells

80
Q

What stimulates release of incretins

A

Endothelial cells in gut in response to to eating

81
Q

Action of incretins

A

Amplifies insulin response to glucose

82
Q

Incretins examples

A

Glucagon-like peptide 1
Glucose dependent insulinotrophic peptide 1

83
Q

What binds to insulin secretory granules causing their release

A

Ca2+

84
Q

Mechanism of insulin release

A

GLUT2 on beta cells has low affinity for glucose
When glucose is HIGH, enters cell
Undergoes metabolism to produce glucose-6-phosphate
ATP then acts on KATP channels and inactivates them
Membrane depolarises
Ca2+ voltage gated channels open so influx of Ca2+
Binds to secretory granules causing release

85
Q

What does the conversion of glucose to glucose-6-phosphate require

A

ADP and hexokinase

SUGER (17 decks)

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