Endocrine functions of pancreas and diabetes mellitus Flashcards
Wk 8
1
Q
What does the Acini tissue secrete?
A
Digestive juices in the duodenum
2
Q
What are the two major tissue types of the pancreas?
A
Acini and islets of Langerhans
3
Q
What does the Islets of Langerhans secrte?
A
pancreatic hormones
4
Q
What hormones are secreted by the pancreas?
A
insulin, glucagon, somatostatin, pancreatic polypeptide, amylin and ghrelin
5
Q
What are the five cell types of the pancreas and how much of the pancreas do they make up?
A
Alpha cells – 25%
Beta cells – 70%
Delta cells – less than 5%
PP cells (F cells) - trace amounts
Epsilon cells
6
Q
What do alpha cells secrete?
A
Glucagon
7
Q
What do beta cells secrete?
A
isnulin and amylin
8
Q
What do delta cells secrete?
A
somatostatin
9
Q
What do PP or F cells secrete?
A
Pancreatic Polypeptide (PP)
10
Q
what does epsilon cells secrete?
A
Ghrelin
11
Q
Where are bet cells more abundant?
A
in the centre of the islet.
12
Q
Where are alpha and delta cells most abundant?
A
in the periphery of the pancreas
13
Q
can cels within an islet influence the secretion of other cells?
A
yes
14
Q
How does cells within an islet communicate?
A
Via gap junctions
15
Q
How does hormones produced by alpha, beta and delta cells regulate each-other’s secretion?
A
paracrine and cell-cell interactions
16
Q
What does insulin secreted from B cells inhibit?
A
glucagon secretion
17
Q
What does glucagon activate?
A
Insulin and somatostatin secretion
18
Q
what does somatostatin inhibit?
A
Glucagon secretion
19
Q
What does Ghrelin inhibit?
A
Insulin secretion
20
Q
What is the biosynthesis of insulin?
A
PrePro Insulin Proinsulin Insulin and C peptide
21
Q
What does the amount of C peptide give?
A
measure of Beta function
22
Q
What are the two polypeptide chains (A and B) of insulin linked by?
A
Disulfide linkages
23
Q
How is glucose transported into beta cells?
A
via facilitated diffusion using the GLUT 2
24
Q
What increases insulin secretion?
A
Increased blood glucose
Increased blood AA and FFA
GI hormones
Glucagon, GH and cortisol
Beta adrenergic stimulation
Sulfonyluera drugs
25
What decreases insulin secretion
Decreased blood glucose
Fasting
Somatostatin
Alpha adrenergic activity
Leptin
K + depletion
26
What is the structure of the insulin receptor?
glycoprotein
Heterotetramer with a a and beta subunit complex
27
What subunit of the glycoprotein binds to insulin?
a subunit
28
What is the mechanism of action for insulin?
Insulin binds to a subunit on outside of cell --> autophosphorylates portions of b sub units within the cell. --> activation of tyrosine kinase --> phosphorylates insulin-receptor substrates --> signal activates cascade of kinases (Ras-MAPK) to stimulate gene transcription, protein synthesis and mitotic activity.
29
What does the autophosphorylation of B subunits of in glyoprotein activate?
a local tyrosine kinase that phosphorylates enzymes
30
Where is the Glut 4 transporter mostly expressed?
Adipocytes and muscle cells
31
What is the Glut 4 transporter?
a glucose transporter that has a high affinity for glucose and transports it down the concentration gradient.
32
What are the actions of insulin on protein metabolism?
Increased amino acid uptake
Promotion of protein synthesis
Inhibition of protein degradation
33
What are the impacts of insulin on protein metabolism just in the liver?
inhibits the breakdown of amino acids to form glucose
34
How does insulin impact carbohydrate metabolism in adipocyte tissue and muscle cells?
Increases carrier mediated uptake of glucose into skeletal muscle and adipose tissue
increases glycolysis
35
How does insulin effect carbohydrate metabolsim?
Increased carrier mediated uptake of glucose into skeletal muscle and adipose tissue
Increased glycogenesis in muscle and liver
Increases glycolysis in adipose and muscle
Decreased gluconeogenesis
Decreased glycogenolysis
36
How does insulin impact fat metabolism in adipose tissue?
increases storage of triglycerides via inducing lipoprotein lipase
Increases storage of fatty acids
37
How does insulin impact fat metabolism in the liver?
Inhibits breakdown of fatty acids into ketones
Increases synthesis of triglycerides, cholesterol and very-low-density lipoproteins.
38
What are some other (non metabolic) actions of insulin?
Required for growth (with GH) (diabetes in children = failure to grow)
Direct effect on hypothalamic satiety
Increases K uptake = temporary relief of hyperkalaemia
Increases sodium retention by kidney
39
What are the consequences of glucagon in insulin deficiency?
insulin contributes signficantly to hyperglycaemia and ketosis
40
What is the origin of glucagon?
alpha cells of islets of langerhans
41
what is the structure of glucagon?
hyperglycaemic hormone, single polypeptide
42
what stimulates release of glucagon?
hypoglycaemia
43
What is the primary and lesser target for Glucagon?
Primary target= liver
Lesser target = adipose tissue
44
What are the main actions of insulin?
Acts to OPPOSE insulin
Increases blood glucose
increased glycogenolysis
increases gluconeogenesis
Increases lipolysis
45
what factors increase glucagon secretion?
Decreased BGL
Amino acids
Acetyl Choline
Catecholamines
46
What factors decrease glucagon secretion?
Fatty acids
Insulin
Somatostatin
47
What is the impact of glucagon on fat metabolism?
Inhibits storage of triglycerides
Activates adipose cell lipase
Increased fatty acids available for other tissues (ketogenic)
48
What is the impact of glucagon on carbohydrate metabolism?
Increases gluconeogenesis (increased uptake of amino acids)
Increased glycogenolysis
Breakdown of liver glycogen
49
What does a high concentration of Glucagon do?
enhances strength of heart
increases blood flow into some tissues
increased bile secretion
inhibits gastric secretion
50
What is the mechanism of action of Glucagon?
Glucagon activates G protein --> AC --> increased concentration of cAMP --> activates PKA --> phosphorylates multiple enzymes --> activates glycogen phosphorylase --> increased glycogenolysis
51
What happens when PKA deactivates glycogen synthase?
decreased glycogen synthesis
52
Where does somatostatin come from?
delta cells
53
What does somatostatin inhibit?
insulin, glucagon and pancreatic polypeptide secretion
54
what are some actions of somatostatin (apart from inhibition)
prolongation of gastric emptying time,
decreased exocrine pancreas secretion, gastric motility and gastric secretion
55
Where is pancreatic polypeptide secreted from?
F cells or PP cells
56
What does Pancreatic Polypeptide inhibit?
insulin and somatostatin secretion.
57
What is Amylin? (structure)
islet amyloid polypeptide
37 AA
co-secreted with insulin from pancretic beta cells
58
When co-secreted from beta cells with insulin, what does Amylin do?
decreases glucagon release, decreased body weight (inhibition of food intake) and decreases gastric emptying
59
How does Amylin affect blood glucose concentration?
decreases glucagon release (decreases blood glucose via inhibition of hepatic glucose production)
60
What are incretins?
Digestive tract hormones that increase insulin secretion from beta cells
61
What are the two major incretins?
Glucagon-like peptide and Glucose-dependant insulinotropic polypeptide (PIC).
62
What releases gastroinstetsinal peptides (GLP-1 and GIP), insulin and amylin?
ingestion of food
63
Where is GLP1 produced?
L cells of small intestine
64
What is the main action of GLP-1?
stimulation of glucose-dependant insulin release from pancreatic islets
65
What happens to GLP-1 in type 2 diabetes?
impaired insulin response to GLP-1 = reduction in postprandial GLP-1 secretion
66
What is the action of GIP in the fasting state (hypoglycemia)?
enhances glucagon activity
67
what is GIP stimulated by?
glucose, fat and protein ingestion
67
What is the action of GIP in hyperglycemia?
potentiates (increases) glucose-induced insulin secretion
68
what is the normal blood glucose range for fasting and random?
fasting = 3.0 - 6.9 mmol/L
random = 3.0-8.0mmol/L
69
When is Growth hormone in blood glucose regulation and what does it do?
Hypoglycaemic trigger
decreased glucose and increased fat use
70
When is cortisol triggered in BGL regulation and what does it do?
hypoglycaemic trigger
decreased glucose uses and increased fat use
increased gluconeogenesis, hepatic glycogenesis sand ketogenesis
71
what are the most common causes of diabetes?
defect insulin secretion, defect insulin action or both
72
Describe the physiology of how thirst and polyuria occurs in type 1 diabetes Mellitus.
Increased blood glucose --> Increased filtered load of
glucose --> The non-reabsorbed glucose acts as an osmotic
solute in urine, producing an osmotic diuresis, polyuria,
and thirst
73
What is insulin deficiency?
from the destruction of pancreatic-B cells
caused by 'organ specific' autoimmune disease
74
What does insulin deficiency (and glucagon excess) result in?
Decreased glucose uptake
increased protein catabolism
increased lipolysis
75
What is the consequence of decreased glucose uptake?
Hyperglycaemia, glycosuria, osmotic diuresis, electrolyte depletion
76
What does thyroid hormone do for BGL?
makes them raise because it increases glucose absorption
77
What is the consequence of increased protein catabolism in insulin deficiency?
increased plasma amino acids
nitrogen loss in urine
and all decreased glucose uptake consequences
(Hyperglycaemia, glycosuria, osmotic diuresis, electrolyte depletion)
78
What is the consequence of increased lipolysis (insulin deficiency)?
Increased plasma FFA, ketogenesis, ketouria and ketonemia
79
What is hyperglycaemia due to?
Decreased insulin action
–Increased insulin production
(Hyperinsulinemia)
* Leads to beta cell failure
80
what percent of diabetes are type 2?
90%
81
What is insulin resistance?
– impaired biological response to insulin
Insulin is secreted normally by the beta
cells
– But insulin can not activate its receptors in
the target cells
82
what is the primary defect for patients with type 2 diabetes?
insulin resistance
83
what are the main differences between type 1 and type 2 diabetes?
Type 1 = insulin dependant whilst type 2 is non insulin dependent
type 1 = severe symptoms of thirst and ketoacidosis whilst type 2 = insidious onset of symptoms
type 1. = spontaneous ketosis but type 2 = no ketoacidosis
Type 1= c-peptide absent, 2 = c-peptide present
84
When should we medically consider Type 1 Diabetes Mellitus?
If there is:
Ketonuria
polyuria
weight loss
young age
family history of autoimmune disease
rapid onset of symptoms
85
What is the difference between insulin deficiency and insulin resistance ?
deficiency = don't actually make it because beta cells are destroyed
resistance = make it but does not activate receptors in target cells
86
What is diabetes insidious vs mellitus
Insipidus= very diluted urine = ADH deficiency
Mellitus= sweet urine due to excess glucose secreted = insulin inactivity
87
What do GH, Corisol and Thyroid hormone all do?
Hyperglucemic hormones = incerased blood glucose levels
88
Describe the sequence of actions if there is Increased BG?
Alpha cell inhibited = decreased glucagon
Beta cell activated = increased insulin
= deceased to normal levels
89
Describe the sequence of actions if there is decreased BG?
alpha cell activated = increased glucagon
beta cell inhibited = decrased insulin
= raise to normal levels
