Lecture 16: Endocrine Pancreas Flashcards
what are the 4 musketeers of glycemic control
- Liver
- Adipose tissue
- pancreas
- muscle
all work together to regulate blood glucose levels
islands of endocrine cells in a sea of exocrine tissue
Islets of langerhans
main endocrine cell types
- β cells (60%)
- α cells (25%)
- δ (10%)
- gamma
- epsilon
Beta cells secrete what hormones
insulin and Amylin
alpha cells secrete what hormone
glucagon
increased blood glucose casuses a decrease in __________ and an increase in ___________
decreased glucagon
increased insulin
decreased blood glucose levels cause a ________ in glucagon and a ______ in insulin
increased glucagon
decreased insulin
amylin is a hormone secreted by _____ that acts on the CNS to ……
B cells, suppresses appetite
delta cells secrete what hormone and what does it do
Somatostatin, it inhibits digestive function, inhiits α and β cells
gamma cells secrete what and what does it do
Pancreatic polypeptide, inhibits gastric juices, appetite and food intake
Epsilon cells secrete what and what does it do
Ghrelin, appetite stimulating hormone
C-peptide is a marker of _____ production and ______ cell function
Insulin production and β cell function
food intake leads to an increase in….
- blood glucose concentration
- increased blood amino acid concentration
- increased GI hormones
- increased parasympathetic stimulation
sympathetic stimulation (and epinephrine) block ____ cells via α-adrenergic stimulation
β cells
insulin secretion leads to…
- decreased blood glucose
- decreased blood fatty acids
- decreased blood aas
- increased protein synthesis
- increased fuel storage
proinsulin is cleaved into ____ and _____
insulin and C-peptide
how does glucose stimulate insulin release?
excitation-secretion coupling in βcells
what are the steps of Excitation-secretion coupling in βcells
- glucose depolarizes cell membrane
- Glu enters via GLUT2
- Glucose+PO43- –> Glucose-6-phosphate
- G6P oxidation –> ATP
- ATP closes K channel
- decreased K flux depolarizes cell membrane
- Voltage gated Ca channels open
- Ca enters β cell
- Ca triggers exocytossi of insulin vesicles
- insulin is secreted into circulation
what are some other humor factors that stimulate insulin release (besides glucose)
- other sugars (fructose, mannose, ribose)
- amino acids (leucine, arginine)
- hormones (glucagon, secretin)
- drugs (sulfonylurea, theophylline)
- short chain fatty acids
- ketone bodies
carbohydrates ____ blood glucose and ____ storage
decrease blood glucose
increase storage
Lipids ____ blood fatty acids and ____ storage
decrease fatty acids
increase storage
proteins ____ blood amino acids and _____ storage
decrease, increase
GLUT____transports glucose across the BBB
GLUT 1
GLUT_____transports glucose in kidney and intestine
GLUT2
GLUT____transports glucose into neurons
GLUT3
GLUT____is an insulin-dependent glucose transporter in most other cells of the body: adipose tissue and resting muscle cells
GLUT4
glucagon gets inhibited by…
high glucose
somatostatin
glucagon is stimulated by…
- low glucose
- epinephrine β2
- vagal stimulation
- amino acids
where is glucagon expressed?
in the liver, intestine, brain and pancreas α cells
produced as proglucagon
proglucagon is proteolytically processed to yield_____ and______
glucagon + incretin(GLP1)
GLP1 (incretin) is released from the intestine in reponse to…
high levels of glucose in the intestinal lumen
incretin (GLP1) increases ________ release from beta cells
insulin
glucagon mainly targets the ______ to stimulate ________ which increases plasma glucose levels
LIVER to stimulate hepatic glucose output
glucagon opposes the effects of_______and increases gluconeogenesis and _________-
insulin, glycogenolysis
What increases glucagon release
- hypoglycemia
- epinephrine, CCK, vagal stimulation, fasting, exercise
- dietary protein (arginine) in absence of carbohydrates (if a meal is protein+carbs, no effect on glucagon)
when CHO is a fuel source….. ________Increases and ___________ decreases
insulin increases
glucagon decreases
when proteins are a fuel source… _______ increases in response to amino acids and ________ increases in response to low blood sugar
insulin, glucagon
where does gluconeogenesis and glycogenolysis occur
liver
what causes the release of somatostatin
high fat, carbs and protein rich means
reduces secretion of glucagon and insulin
pancreatic polypeptide is secreted by what cells
γ(gamma)Cells
what does pancreatic polypeptide do
inhibits secretion of pancreatic enzymes, hepatic glycogen and constriction of the gall bladder
what stimulates the release of pancreatic polypeptide
fasting
intestinal hormones (cholecytokinin, secretin, gastrin)
stimulation of vagus nerve
ingesting protein
what decreases pancreatic polypeptide
glucose and somatostatin
what are some diabetogenic hormones besides glucagon
- epinephrine
- cortisol
- growth hormone and IGF-1
- pancreatic polypeptide
all generally OPPOSE INSULIN
what is the role of the brain in hypothalamic control of fuel management
autonomic control of hormone release
sesnes nutrients and hormones associaated w/ nutrient levels
insulin, leptin, GLP-1 to drive appetite
(within neural control of glucose) glucose detection occurs in the_______ Nucleus
Arcuate
type I diabetes is _____ dependent and occurs due to a lack of _______ secretion from the pancreas
insulin dependent
insulin
Type I DM has autoimmune effects….
T-cells destroy beta cells
Type II diabetes is _____________ dependent, tissue resistance to insulin
non-insulin dependent
what type of DM is often the result of diet/activity
type II
acute symptoms of DM
- elevated blood glucose
- characteristics of post-absorptive state (like having just eaten a meal but all the time)
Chronic effects of DM
retinopathy (cataracts in dogs)
pancreatic amyloidosis (cats)
neuropathy
nephropathy
cardiovascular disease
**KETOACIDOSIS
occurs as a consequence of increased appetite
polyphagia
occurs in attempt to compensate for dehydration
polydipsia
hyperglycemia results form ….?
inadequate uptake of glucose into cells and an increased output of glucose from liver
glucosuria
elevated glucose in glomerular filtrate is greater than what the tubular cells can reabsorb in the nephron
what does the osmotic effect of glucosuria cause
draws additional water into filtrate = excess fluid is lost from the body resulting in dehydration
hepatic use of fatty acid results in…?
ketosis
ketone bodies in the blood disrupt blood pH, resulting in _______
metabolic acidosis
what results in muscle wasting in DM
insulin deficiency causes increased protein degradation which causes muscle wasting + weight loss
an excess of insulin results in….
hypoglycemia (low blood glucose)
effects are dangerous + manifest early in the brain
- loss of consciousness, depressed brain function
- weakness, fatigue, ataxia
cats suffer nearly exclusively from type ____ diabetes?
type II
insulin excess results in one of 3 ways….
- insulin overdose (give carbs)
- reactive hypoglycemia (in an extreme response to glucose, beta cells release too much insulin)
- islet tumor in dogs (excessive insulin release)
- most common type of hypoglycemia in dogs
- typically episodic
treatment for DM in felines
insulin therapy every 12 hrs
diet therapy: low carbohydrate diet for life
