Physiology Ii - Endocrinology

Front 1

How does glucagon increase blood glucose levels?
(what 3 processes?)

Back 1

1.Stimulation of hepatic glycogenolysis -> blood glucose levels can double within minutes
2.Stimulation of hepatic gluconeogenesis (via increased amino acid uptake)
3.Stimulation of lipolysis in fat tissue in very high concentrations

Front 2

Which type of diabetes is potentially reversible?

Back 2

Diabetes type 2

Front 3

Two types of hormones (in terms of where originate):

Back 3

1. Tissue hormones - produced by individual endocrine cells; not in large glands
2. Glandular hormones - e.g. cytokines

Front 4

Which 2 organ systems produce the most hormones?

Back 4

1. CNS (brain)
2. GI

Front 5

What are endocrines or hormones? functions?

Back 5

Produced in a gland and secreted directly into circulation w/o ducts

chemical messangers, regulators of homeostasis and metabolic pathways, etc.

Front 6

autocrine hormones

Back 6

affect cell of production

Front 7

Are endocrine hormones present in high concentrations?

Back 7

No, always in extremely low concentration (pg - ug/ ml), which why they are difficult to detect.

Front 8

4 Types of hormones in terms of chemical structure?
(e.g. peptide hormones, and ? )

Back 8

1. peptide hormones (like insulin)
2. steroid hormones (e.g. vit.D)
3. amines (e.g. dopamine, epinephrine)
4. eicosanoids (e.g. prostaglandins)

Front 9

which hormone type is most common?

Back 9

peptide hormones

Front 10

what hormones are hydrophilic?

Back 10

peptide hormones

Front 11

which hormones are lipophilic?

Back 11

steroid hormones

Front 12

What is term Dr. Zeigler uses for parts of hormone precursor which are cleaved off during protein/peptide synthesis? Are these cleaved off pieces ever active on their own?

Back 12

pre-pro sequences; can be active compounds also!

Front 13

What are differences between nervous and endocrine system?

Back 13

endocrine system is slower to react, much slower, because it relies on chemical messengers

also endocrine system responds to INTERNAL stimuli; while nervous system responds to external ones.

Front 14

How long (approx.) does it take protein hormone to be produced?

Back 14

~45-60 minutes

Front 15

How long does it take for protein hormone to be released?

How are hormones released so quickly, when protein synthesis takes so long?

Back 15

2-5 minutes

* b/c after prepro seq. cleaved off, hormone stored in secretory granule or vesicle where can secrete immediately upon stimulation via exocytosis

* also hydrophilic so dissolves easily in plasma

Front 16

What type of hormones made in adrenal cortex:
A. peptide hormones?
B. steroid hormones?
C. amines?
D. eicosanoids?

Back 16

* hormones made in adrenal cortex are steroid h's
e.g. mineralocorticoids (aldosterone) and glucocorticoids (cortisol).
* also a secondary site of androgen synthesis.

Front 17

True or false: Protein hormones generally have longer half-life then steroids.

Back 17

False, b/c proteases are found everywhere in tissues, esp. concentrated in blood flow of liver&kidney.

Front 18

Steroid Hormones are derived
from ? In one sentence, describe how made.

Back 18

Steroid Hormones are derived
from Cholesterol

* stimulus activates enzymes -> starts a series of 3 conversions to produce steroid hormones

Front 19

How are steroid transported in plasma?
What % of bound?

Back 19

* not hydrophilic, are lipophilic, so need to attach to carrier (like albumin) in plasma

1-10% are in free form=active; rest is bound=inactive (acts as a hormone reserve in plasma)

Front 20

Why is half life of steroids extended (last longer than peptide hormones)?

Back 20

* binding to albumin helps protect steroids from degradation and quick destruction in liver (longer half-lives -> hours to days)
* also makes "reservoir" in circulation

Front 21

How are most steroids metabolized?

Back 21

glucuronidation in liver

Front 22

How tissues get cholesterol?
Flows around body in what form?

Back 22

* from diet (although can be converted from Acetyl CoA)
* TriG and cholesterol all condensed into VLDL
* LPL off loads cholesterol in tissues making steroids

Front 23

Receptor location for hydrophilic hormones?
Describe these receptors; are they complex?

Back 23

* Cell membrane (cannot diffuse through); so receptor on surface of membrane
* most of these receptors are very large and complex w/external binding portion and internal transducing portion

Front 24

Receptor location for lipophilic hormones:

Back 24

* Cytoplasm or Nucleus; receptor inside target cell b/c lipophilic hormones have no problem entering cell to bind to it

Front 25

All hormones affect their target tissues by forming first a ________ , which alters the activity of their target cells.

Back 25

HORMONE - RECEPTOR complex

Front 26

We know number of particular receptor can increase and decrease; which is more common: up regulation or down regulation?

Back 26

down regulation

Front 27

What is example of up regulation of receptor number?

Back 27

Example: Aldosterone (steroid) initiates synthesis of enzyme ATPase in its target cells -> stimulates Na/K pumps

Front 28

True or false: Antagonist does opposite action of hormone.

Back 28

False, antagonist simply blocks binding of hormone to receptor.

Front 29

Lipophilic hormones induce protein synthesis, w/newly formed proteins being mostly enzymes, which now stimulate or inhibit certain metabolic pathways = ?

Back 29

= METABOLIC EFFECT

Front 30

In following example: which represents the secondary messanger?

Back 30

cAMP

Note: The first messenger (= hormone) remains outside of its target cell b/c cannot enter, but transmits its message via cAMP = second messenger

Front 31

phosphorylation is usually stimulatory or inhibitory event?

Back 31

stimulatory

Front 32

This an example of a _______feedback loop: effect of plasma glucose levels on glucagon secretion

Back 32

NEGATIVE FEEDBACK LOOP

Front 33

What is stimulated (to start) if glycogen stores are full?

Back 33

lipogenesis, creation of fat

Front 34

What cells are not affected by insulin? (examples)

Back 34

glucose independent cells

neurons, retina, lens, blood
cells, pancreatic B cells, kidney,
GI mucosa, placenta

Front 35

?% of body cells contain insulin
receptors

Back 35

80% of body cells contain insulin
receptors = insulin-sensitive tissues

Front 36

Where is insulin receptor located?
what type of mechanism?

Back 36

* its a protein, so on cell membrane
- called a tyrosine kinase
* 2nd messanger mechanism (these are usually G-coupled) but not sure
* insulin binds to external part alpha subunit, and stimulates beta subunits

Front 37

After insulin – receptor binding (= in
insulin-sensitive tissues): what happens?

Back 37

Beta parts of receptor become the
activated tyrosine kinase (= second messenger)
-> leads phosphorylation of various enzymes

Front 38

What is stimulated by insulin binding?

Back 38

* glucose uptake by GLUTs
* fat uptake and storage in fat tissue via lipoprotein lipase enzyme - extracts fat from VLDL or chylomicrons
* inhibits hormone specific lipase
* inhibits proteases / proteolytic enz. / protein brk.down
* stim. protein temporary storage and synthesis (organ function, growth, clotting factors & albumin in liver)

Front 39

What happens without w/o insulin, but with circulating chylomicrons?

Back 39

LDL not active, full of chylomicrons

Front 40

Glucagon opposes Insulin effects on _____ in the LIVER


Glucagon ____ blood glucose level

Back 40

Glucagon opposes Insulin effects on carbohydrate metabolism (which were storage, breakdown)

Glucagon INCREASES blood glucose level

Front 41

How does glucagon increase blood glucose levels?
(by stimulating what 3 processes?)

Back 41

1.Stimulation of hepatic glycogenolysis -> blood glucose levels can double within minutes
2.Stimulation of hepatic gluconeogenesis (via increased amino acid uptake)
3.Stimulation of lipolysis in fat tissue in very high concentrations

Front 42

What might stop glucagon from secreting?

What cells are involved?

Back 42

high blood glucose, like after high carb. meal

(pancreatic alpha cells are insulin-sensitive: high plasma glc -> high insulin ->
glc uptake into alpha cells -> glucagon secretion is inhibited!)

Front 43

Main signal for glucagon release

Back 43

HYPOGLYCEMIA -> stimulates glucagon secretion

Front 44

high plasma amino acid levels ___ glucagon secretion

Back 44

also stimulate glucagon secretion

but only when blood glc levels are low (A.A. are then channeled into gluconeogenesis)

Front 45

= IDDM

Back 45

Type I DM
circulating insulin levels are low

Front 46

What causes Type I DM?

Back 46

Causes: islet cell destruction b/o pancreatitis, senile degeneration, autoimmune disease -> hyperglycemia (b/c low insulin; cells can't take up glc.)

Front 47

Definition of Diabetes Mellitus:

Back 47

absolute or relative lack of insulin leading to impaired
carbohydrate, lipid and protein metabolism

Front 48

Non-insulin dependent DM =

Back 48

Type II DM

Front 49

Causes of Type II DM?

Insulin resistance?

Back 49

* something goes wrong with insulin receptors, not binding insulin right, or not enough of them
* insulin present but not responding to it; known as insulin resistance aka "relative" lack of insulin

Front 50

%2 of ___ suffer from diabetes m.

Back 50

%2 of burmese cats

Front 51

Are beta cells of pancreas intact in type 2 diabetes?

Back 51

yes at first, insulin still being made in excess as way to compensate blas
eventually the beta cells become "exhausted" and type I diabetes develop

Front 52

Secondary type diabetes or type 3 diabetes

Back 52

high levels of other hormones like cortisol
high glucagon

Front 53

Which type of diabetes has normal insulin levels?

Back 53

Type II DM

Front 54

Which hormone responds to high osmoregularity in plasma? causes what?

Back 54

ADH, causes incr. in thirst

Front 55

two initial clincal signs of diabetes?

Back 55

1a. rapid weight loss
(b/c of excess lipolysis, proteolysis), 1b. polyphagia (b/c body thinks it's hypoglycemic)
2. glucosuria

Front 56

What is consequence of excess lipolysis?

Back 56

Excessive Lipolysis -> FATTY LIVER and KETOACIDOSIS -> diabetic COMA

FYI: Ketones produced when FA broken down in liver. Before this FA are enz. broken down via β-oxidation to form acetyl-CoA. However, if conditions not right for TCA cycle (intermediates not present), A/CoA become ketones instead.. In high lvl. lower pH of blood, leading to 'ketosis'

Front 57

Glycated Proteins/Acidosis/Proteolysis/Swelling further lead to?

Back 57

* vascular damage -> microangiopathies / neuropathies
(e.g. glomerula, TIBIAL nerve/cat, retina/humans)

Front 58

What is consequence of weight loss and proteolysis?

Back 58

proteolysis -> WEIGHT LOSS, muscle weakness and reduction of organ functions

Front 59

At what glc. plasma level will glucose start appearing in urine?

Back 59

if over 180mg/dL

Front 60

what 2 clinical signs of diabetes usually appear as a result of glycosuria?

Back 60

1. polyuria
2. polydipsia (incr. thirst)

Front 61

Does polyphagia (as hypothalamic satiety centre is insulin-dependent) continue?

Back 61

initially only as hypothalamic satiety centre is insulin-dependent; later anorexia and vomiting following tissue damages a/o acidosis

Front 62

What tissues get too much glucose with diabetes?

Do do these tissues with excess glucose?

Back 62

insulin independent tissues (neurons, liver, RBC, etc.)

do not have a lot of glucogen storing ability, also cannot convert to FAs
~form complexes w/proteins -> glycated proteins

Front 63

Are glycated proteins functional?

Examples?

Back 63

No

glycated hemaglobin! (A chain more often that B chain), after ~6 wks. of hyperglycemia

Front 64

What are glycated proteins in plasma called (e.g. glucosa + albumin)?
Time frame? (like when does this start to happen?)

Back 64

fructose amines

2 weeks

Front 65

What glycated protein test is most frequently done in vet medicine?

Back 65

fructose amine test, for detecting glc. & albumin complexes

Front 66

In the tissues excess glucose is converted into ___ in the lens?
Eventual consequence of this?

Back 66

sorbitol

H2O acc. in lens, gets cloudy -> nerve damage and blindness

Front 67

What are animals with diabetes prone to UTI?

Back 67

tract has lots of sugar in it

Front 68

which type of diabetes most common in cats?

Back 68

DM type 2

Front 69

how would u treat DM type 1?

Back 69

give insulin

Front 70

Why do u have to inject insulin?

Back 70

have to inject all peptide hormones otherwise get degraded by the acid in stomach, etc.

Front 71

why are steroid able to taken as pills?

Back 71

lipophilic

Front 72

what maintenance diet wud you feed animal with diabetes?

Back 72

high in quality protein, low soluble carbs, low FA (b/c often obesity is cause, and leads to fatty liver), high in fiber

Front 73

Which type of diabetes is potentially reversible?

Back 73

diabetes type 2

Front 74

how would you treat T2 diabetes to begin recovery process and why?

Back 74

would give insulin along with exercise so BW reduced; this gives exhausted beta cells in pancreas (have churning out extra insulin) a chance to recover and make insulin again on own

Front 75

What must be functional in animal to recover?
(unanswered questions)

Back 75

* Beta cells can't be completely shot
* Need at least some insulin receptors on insulin dep. tissue
>But aren't receptors the source of problem with T2??

Front 76

What is course of action if animal recovers from T2 diabetes? (What would you watch for?)

Back 76

* animals blood glucose levels must monitered closely
* if beta cells making insulin again, must reduce or stop insulin supplements
* otherwise can become hypoglycemic

Front 77

Could you cure/reverse type 1 diabetes?

Back 77

Theoretically could do pancreas transplant, but normally only done in human medicine
(remember in type 1 is absolute of insulin, so beta cells not functional at all)

Front 78

How treat diabetes type 3?
(unanswered question)

Back 78

Secondary DM or Type III ( TRANSIENT DM)
* high levels of other hormones like cortisol, or glucagon
* caused by DM Type II; insulin resistance

Does it fix itself?
What is connection between cortisol and insulin/hyperglycemia?

Front 79

If glucagon levels really HIGH, which metabolic pathway favored?

Back 79

lipolysis (2.3.1)

Front 80

Where is glucagon made?

Back 80

secreted in pancreatic
α cells AND stomach <- gut glucagon

Front 81

Half life of glucagon?

Back 81

5 minutes (it's a peptide - shorter half life than steroid, b/c proteases are everywhere)

Front 82

How are pancreatic alpha cells and beta cells different aside from the hormones they make?

Back 82

* Beta cells are insulin independant (they just make it)
* alpha cells are insulin dependent

Front 83

What happens when insulin binds alpha cells?
(unanswered question)

Back 83

glucagon secretion stops being released
(remember peptide hormones stored, so inhibiting synthesis..i dont think)

Front 84

Name two most common health problems affects in ferrets:

Back 84

1. Adrenal disease - excess sex steroids

2. Insulinoma - tumor in beta cells of pancreas

Front 85

True or False: Regarding adrenal disease in ferrets, characterized by rise in cortisol & aldersterone.

Back 85

False!

Ferrets w/adrenal disease have excess sex steroids (estrogens > androgens); but cortisol & aldosterone are normal

Front 86

Symptoms of Adrenal disease in ferrets?

Back 86

Ferret with Adrenal Disease:
estrogens > androgens:

symptoms include alopecia, enlarged vulva, prostate hypertrophy, sexual aggression, bone marrow depression (anemia)

Front 87

True or False: Insulinoma in ferrets causes rapid increase in blood glucose

Back 87

False!!!

Insulinoma in ferrets causes rapid DROP in blood glucose

because more insulin secreted