Lecture 16: Endocrine Pancreas Flashcards
1
Q
What are the four “musketeers” of glycemic control
A
Liver, adipose tissue, pancreas and muscle
2
Q
Islet of langerhans
A
Endocrine pancreatic cells
3
Q
What are the two main regulators of glucose- what cell type and hormone
A
- Beta cells-insulin
- Alpha cells- glucagon
4
Q
Insulin and glucagon are the dominant hormone regulators that shift the body between ____
A
Anabolism and catabolism/glucose sparing
5
Q
What cell type is activated during an increase of blood glucose and which is inhibited
A
Activated: Beta cell to release insulin and decrease BG
Inhibited: alpha cell, decrease glucagon
6
Q
What cell type is activated during a decrease in BG and which is inhibited
A
Activated: alpha cell to release glucagon and increase BG
Inhibited: beta cell, decrease insulin
7
Q
What two hormones do beta cells secrete
A
Insulin and amylin
8
Q
What hormone do alpha cells secrete
A
Glucagon
9
Q
What hormone do delta cells secrete
A
Somatostatin
10
Q
What hormone do gamma cells secrete
A
Pancreatic polypeptide
11
Q
What hormone do epsilon cells secrete
A
Ghrelin
12
Q
What does amylin do
A
Acts on CNS to suppress appetite
13
Q
Which hormone inhibits digestive function, inhibits alpha and beta cells
A
Somatostatin
14
Q
What do pancreatic polypeptides do
A
Putatively inhibit gastric juices, appetite and food intake
15
Q
What does ghrelin do
A
Stimulates Appetite
16
Q
Describe the flow chart of insulin regulation upon food intake
A
- Food intake causes—>
- Increase BG, increase GI hormones and increase AA which all act on—>
- Activate islet B cells
- Insulin secretion
- Decrease: BG, FA, and AA
Increase: protein synthesis and fuel storage
17
Q
What type of hormone is insulin
A
Peptide
18
Q
Describe the synthesis of insulin
A
- Preproinsulin in mRNA strand
- Enters ER with C peptide attached
- Enters golgiand trans Golgi to have cleavage of C-peptide from insulin
- C peptide and insulin put in secretory granules
19
Q
What are the secretory products in granules
A
1:1 insulin: C-peptide
5% pro insulin
20
Q
What is C-peptide a good marker for
A
Insulin production and B cell function
21
Q
What mechanism allows glucose to stimulate insulin secretion and in what cell type does this occur
A
Excitation-secretion coupling in Beta cells
22
Q
Describe the steps in how glucose stimulates insulin release
A
- Glucose enters via GLUT2
- Close K + channels which depolarizes cell
- VG Ca2+ channels open and enter Beta cell
- Ca2+ triggers exocytosis of insulin vesicles into circulation
23
Q
What are some other humoral factors that stimulate insulin release besides glucose
A
Sugars, amino acids, hormones, drugs, short chain fatty acids, ketone bodies
24
Q
How does insulin effect carbohydrate energy stores
A
Decrease BG, increase storage
Increase glucose uptake
Increase glycogenesis
Decrease glycogenolysis
Decrease gluconeogenesis
25
How does insulin effect lipid energy stores
Decrease blood FA, increase storage
Increase glucose uptake by adipocytes
Increase lipogenesis
Increase FA uptake
Decrease lipolysis
26
How does insulin effect protein energy stores
Decrease blood amino acids, increase storage
Increase amino acid uptake
Increase protein-synthesizing machinery
Decrease protein degradation
27
What is GLUT1 used for
Transports glucose across the BBB
28
What is GLUT2 used for
Transports glucose in kidney and intestine
29
What is GLUT3 used for
Transports glucose into neurons
30
What is GLUT 4 used for
Insulin dependent glucose transporter in most other cells of the body: adipose tissue and resting muscle cells
31
What is the consequence to low levels of insulin secretion
Hyperglycemia
32
What are some MAP kinase pathways that insulin regulates
1. Fuel storage
2. Alter gene expression pathways
3. Enhance cell growth and phenotypes
33
Glucagon is inhibited by___ and ____
High glucose
Somatostatin
34
Glucagon is stimulated by what 4 things
Low glucose, epinephrine (beta2), vagal stimulation, amino acids
35
Where is glucagon expressed
Pancreas alpha cells, liver, intestine and brain
36
Glucagon is produced as pro glucagon and proteolytically processed to yield glucagon and ____
Incretin (GLP1)
37
When/where is GLP1 released
Released from intestine in response to high glucose levels in intestinal lumen
38
GLP1 increases ____ release from B cells
Insulin
39
What is the main target of glucagon
Liver to stimulate hepatic glucose output: increase plasma glucose levels
40
What does glucagon oppose
Insulin and GLP1
41
Does glucagon increase or decrease glyconeogenesis and glycogenolysis
Increase glycogenolysis and decrease glyconeogenesis
42
What is the main factor that drives release of glucagon
Hypoglycemia
43
Does epinephrine, CCK, vagal stimulation, fasting, and exercise increase or decrease circulating glucagon
Increase
44
Does hyperglycemia, somatostatin, insulin, fatty acids, and keto acids increase of decrease glucagon
Decrease
45
In the absence of carbohydrates, does dietary protein increase or decrease glucagon
Increase
*if meal has carbs this doesn’t happen
46
What is glucagons effect on carbohydrate energy stores
Increase BG
Increase gluconeogesis and release from liver
Increase glyconeogenesis
Decrease glycogen synthesis
47
How does glucagon effect lipid energy stores
Increase blood FA and ketones
Decrease triglyceride synthesis
Increase lipolysis and release of FA
Increase Ketone production
48
What effects does glucagon have on protein energy stores
Minimal effect on blood amino acids
Decrease hepatic protein synthesis
Increase hepatic protein degradation and increase gluconeogenesis
49
When carbohydrates are the main fuel source what happens to insulin and glucagon levels
Insulin increases
Glucagon decreases
50
What happens to insulin and glucagon when proteins are the main fuel source
Insulin increases in response to blood AA
Glucagon increases in response to low blood sugar
51
What hormone is secreted in a high protein diet in order to avoid BG crash
Glucagon
52
What type of hormone is somatostain
Peptide
53
What stimulates release of somatostatin
High fat, carbs and protein rich meals
54
How does somatostatin inhibit release of glucagon and insulin
Hyper polarizing alpha and beta cells
55
What does pancreatic polypeptide inhibit
Secretion of pancreatic enzymes, hepatic glycogen, and the contraction of the gallbladder
56
What stimulates the release of pancreatic polypeptide
Fasting, intestinal hormones (cholecystokinin, secretin and gastrin), stimulation of vagus nerve, and ingestion of protein
57
does glucose and somatostain increase or decrease pancreatic polypeptide
decrease
58
What hormone affects weight regulation and obesity based on its rate of release
Pancreatic polypeptide
59
What diabetogenic hormones regulate glucose
Glucagon, epinephrine, cortisol, growth hormone and IGF-1, pancreatic polypeptide
60
How does the brain regulate glucose
Hypothalamic control of fuel management via autonomic control of hormone release
Senses nutrients and hormone levels
61
What hormones are sensed by the brain and drive appetite
Insulin, leptin, and GLP-1
62
Where are the receptors for glucose detection in the brain located
Arcuate nucleus
63
Neural control for glucose operate to control ___ and ____
Energy balance and regulate body composition
64
What disease results in high blood sugar levels over a prolonged period of time
Diabetes Mellitus
65
What is problem in type I DM
Lack of insulin secretion from pancreas
- insulin dependent
66
What are some potential causes of Type I DM
Autoimmune: T-lymphocytes destroy Beta cells
Idiopathic, environmental
Alloxan and streptozotocin are two drugs that selectively destroy Beta cells
67
What is the problem in type II DM
Tissue resistance to insulin
Non-insulin dependent
68
What type of DM is usually a result of diet/activity
Type II
69
What are the acute symptoms of DM
Elevated BG
70
What are some chronic effects of DM
Retinopathy (dogs)
Pancreatic amyloidiosis (cats)
Neuropathy
Nephropathy
CVD
Ketoacidosis
71
Type I is common in what species
Dogs
72
Type II is common in what species
II
73
Insulin deficiency results in hyperglycemia as a result of what 2 things
1. Decrease glucose uptake into cells
2. Increase hepatic output of glucose
74
How does hyperglycemia cause glucosuria, dehydration, and PD
Hyperglycemia overwhelms tubular system so can’t reabsorb all of it, results in it being excreted in urine
Osmotic effect of glucose draws water out into filtrate resulting in excess fluid loss=dehydration and then PD
75
Dehydration results in decreased blood volume and therefore circulatory failure to several vital organs, what happens to brain
Brain function declines due to failure to oxygenate resulting in death
76
What happens to shape of cells in chronic DM
Cells shrink due to osmotic shift of water into ECF and blood
77
What is the effect of chronic DM on nerve cells
Lose their ability to maintain correct membrane potential and form AP
78
Due to decreased insulin and therefore decreased uptake of glucose into tissues what happens to pH
FA are mobilizes and used by liver resulting in ketosis, ketone bodies cause metabolic acidosis
79
What happens to respiratory ventilation in response to metabolic acidosis in DM
Respiratory ventilation increases to vent off CO2 and shift pH up
80
Does lack of insulin cause protein catabolism or anabolism
Catabolism
81
Protein catabolism causes muscles to atrophy and cause amino acids to do what
Amino acids shift towards greater glucogenesis and contribute to existing hyperglycemia
82
Clinical case: 9yr, SF, DLH presents with 5 months progressive weight loss, muscle weakness, matted fur and moderate periodontal disease. Note plantigrade stance on exam. Owner mentions low energy, occasional tremors and PU. USG=1.034. What is most probable diagnosis
Type II DM
83
Clinical case: suspect type II DM cat, what additional tests can be run
Serum fructosamine
84
What can insulin excess cause
Hypoglycemia
85
What are some dangerous effects/symptoms of hypoglycemia
Loss of consciousness, depressed brain function, weakness, fatigue, ataxia
86
What is insulin overdose and what can be given to alleviate
Injection of too much insulin, resulting in shock (decrease BG)
Give carbs to alleviate
87
What is reactive hypoglycemia and what can be done to alleviate it
Extreme response to glucose, beta cells release too much insulin
Limit carb diet to alleviate
88
What can cause reactive hyperglycemia
Islet hyperplasia or lack of somatostatin counterbalance
89
What do islet tumors in dogs cause and what can help alleviate insulin excess
Excessive insulin release give carbs to alleviate
90
What is the most common cause of hypoglycemia in dogs
Islet tumors
