Chapter 78 Flashcards
What two important hormones does the pancreas secrete?
- insulin, Beta cell
- glucagon, alpha cell
What minor hormones does the pancreas secrete?
- amylin: Beta cell
- somatostatin
- pancreatic polypeptide
What does somatostatin do?
inhibits insulin and glucagon
What does pancreatic polypeptide do?
inhibits pancreatic endocrines and exocrines
When is energy abundance hormone elevated? (insulin)
when energy is high
What does energy storage hormone increase? (insulin)
storage of energy
What do hypoglycemic hormone do? (insulin)
acts to reduce blood sugar
What is the dominant hormone in the regulation of blood sugar?
Insulin
How is insulin synthesized?
as a preprohormone after translation of insulin RNA by ribosomes in ER
How quickly is insulin cleared once its circulating in the blood?
10-15 ,
What is insulin degrade into to allow a rapid “turn off”?
insulinase
What is the result of a lack of C peptide?
Type 1 diabetes
- neuropathy
- CVD
- promotes GFR
How does C peptide affect neuropathy?
C peptide promotes axonal repair. With a lack of c peptide axonal repair is impaired.
How does C peptide affect CVD?
C peptide promotes microvascular blood flow by stimulating Na+/K+ pump and the release of NO
Which disease is associated with too much C peptide?
Type 2 diabetes
What happens with too much C peptide?
it deposits on endothelia and causes inflammation
- macrophage to foam cell
- T cell mediated inflammation
- smooth muscle proliferation
What is GLUT-2? and what cells do you find it in?
- it is a concentration dependent glucose transporter
- found in Beta cells
What is glucose influx proportional to?
blood glucose concentration
What is the primary factor in Beta cell stimulation?
increased blood glucose.
How is glucose phosphorylated?
by glucokinase to glucose-6-phosphate
What is the process of insulin secretion?
1) GLUT-2 on pancreatic B cells take up glucose
2) Glucokinase –> G6P
3) NADPH and ATP (from glycolysis) close K+ channel
4) Ca2+ channels open
5) vesicles bind Ca2+ and release insulin to blood
What kind of feedback does glucagon provide to insulin?
negative
What does glucagon stimulate?
Gluconeogenesis
What are some factors in B cell stimulation?
glucagon arginine and lysine GI hormones acetylcholine Sulfonurea drugs
What are the effects of insulin on carbohydrates?
- increased glucose uptake
- increased glycogenesis
- decreased gluconeogenesis
What are the effects of insulin on fat?
- increased triglyceride synthesis
- decreased trigylceride breakdown
What are the effects of insulin on protein?
- increased synthesis
- decreased breakdown
what are the end effects of insulin?
- 80% of cells increase glucose uptake by mobilizing GLUT-4
- Phosphorylation of glucose then allows it to be a substrate for CHO metabolic functions
How does Metformin work?
stimulates AKT pathway to increase GLUT-4 in skeletal muscles to treat hyperglycemia in type 2 diabetes
Why is it important to have low serum insulin level in between meals?
so glucose can go preferentially to brain.
What does insulin stimulate in the liver?
glycogen synthetase and inhibits glycogen phosphorylase in the liver
How is most glucose after a meal stored?
Immediately in liver as glycogen
What does inactivation of glycogen phosphorylase prevent?
breakdown of glycogen
What does insulin decrease?
gluconeogenesis by inhibiting required enzyme action
What does insulin activate?
glucose storage/utilization enzymes (+)
What does insulin inactivate?
glucose mobilization/synthesis enzymes (-)
What are two conditions where muscle uses glucose?
- exercise
- after meal when blood glucose is high and insulin is high.
How much does insulin increase glucose transport to muscle by?
15 times
What happens when liver glucose storage reaches its limit?
insulin causes conversion of excess sugar into fatty acid by the liver. (pyruvate to acetyl CoA)
What does insulin inhibit in regards to adipose?
insulin inhibits hydrolysis of TG, preventing FFA to blood.
Insulin promotes utilization of CHO for energy, but what happens when insulin is low?
FAT is preferentially used (except brain)
What is the signal for switching between CHO and FAT?
blood glucose
Which is used when blood glucose is low and insulin is low? FAT or CHO?
FAT is used
Which is used when blood glucose is high and insulin is high? CHO or FAT?
CHO
How does insulin promote K uptake to decrease serum [K+] ?
1) increase Na+/K+ ATPase
2) increase intracellular Na+ sensitivity
3) Inhibit K+ efflux
What can patients with hyperkalemia be treated with to decrease serum [K+]?
insulin
How does insulin promote phosphate uptake?
kidney has immediate response to phosphate conservation upon insulin stimulated phosphate uptake
What do the beta cells of the pancreas produce? QUICK CHECK
amylin
not somatostatin, insulin, or glucagon and amylin
What are insulins actions on CHO in the liver? QUICK CHECK
glycogen synthesis
Why do insulin and growth hormones make you grow?
each promotes cellular uptake of AAs required for growth.
Which hormones does insulin stimulate the uptake of?
leucine, valine, isoleucine, tyrosine, and phenylalanine
What type of cells secrete glucagon and when?
alpha cells when blood glucose falls.
What are the actions of glucagon?
- increase blood glucose
- hyperglycemic effect (corrects hypoglycemia)
- typically opposes the actions of insulin*
What are glucagons effects on glucose metabolism?
glycogenolysis
-gluconeogenesis
What increases the secretion of glucagon?
- low blood glucose
- exercise
- high serum AAs (same effect as on insulin, but glucagon makes glucose, insulin makes protein)
Why does exercise increase secretion of glucagon?
increased circulating AAs
increased beta-adrenergic stimulation
prevents fall in blood glucose
What is secretion of Glucagon decreased by?
- high blood glucose
- somatostatin
What is amylin secreted by?
pancreatic B cells
What happens if amylin is insoluble?
it forms fibrils and induces apoptosis of pancreatic B cells, thus inhibiting insulin secretion
What happens if amylin is soluble?
it decreases blood glucose –> synergize with insulin, decrease glucagon
What is somatostatin secreted by?
Delta cells of Langerhans
What does somatostatin do?
inhibits glucagon and insulin
What is somatostatin increased by?
ingestion of food –> increase blood glucose, increased AA, increase FA, increased GI hormones
What is the main goal of somatostatin?
- extend period of time over which food/nutrients are assimilated
- decreases use of absorbed nutrients by tissues, making food available over longer periods of time.
What is the critical level for insulin?
< 20-50 mg/100ml
What happens when the critical level of insulin is reached?
hypoglycemic shock
coma
death
What processes slow down dramatically with a lack of insulin?
- Protein storage and synthesis
- increased catabolism of protein —> protein wasting leading to weakness and organ dysfunction
What does increased use of fat for energy by all tissues cause?
(except brain) lipolysis
What does excess use of fat lead to?
oxidation of FA in liver and generation of ketone bodies.
What is diabets mellitus?
syndrome of impaired CHO, PRO, and FAT metabolism
What is DM caused by?
- lack of insulin secretion (DM type 1, IDDM insulin dependent)
- decreased insulin sensitivity of tissues (insulin resistance, type 2 DM, NIDDM non-insulin dependent)
What is type 1 DM?
overt B cell failure –> destruction of B-cell
What is type 2 DM?
loss of insulin sensitivity –> later loss of B-cell u, decreased capacity to secrete insulin
What are some causes of Type 1 DM?
- viral infection
- auto-immune disease
- genetics
When is the typical onset of Type 1 DM?
childhood-early adolescence
What are some clinical findings of type 1?
increased blood glucose - 300-1200 mg/100ml
increased use of fats for energy, cholesterol synthesis
depletion of proteins
How does high blood glucose cause dehydration?
-loss in urine = osmotic diuresis (causes decreased electrolytes in addition to water)
What is the polyol pathway?
glycated protein, loss of normal function, precipitation on tissue “sugar coated proteins”
What does chronic high blood glucose lead to in Type 1 DM?
tissue damage.
1) vascular
2) nerves
3) HTN and atherosclerosis
What are effects of fat metabolism in Type 1 DM?
- hyperventillation increased for expiration of CO2
- increased cholesterol in circulation causes arteriosclerosis
- depletion of protein stores causes weight loss, fatigue, polyphagia, severe wasting, DEATH
When is the typical onset of Type 2 DM?
> 30, usually 50-60
What is type 2 DM associated with?
increased insulin
What are warning signs for type 2 DM?
- obesity, abdominal fat (oh no, SANTA!!!!)
- reactive hypoglycemia
- insulin resistance
- fasting hyperglycemia
- lipid abnormalities
- HTN
What are causes of insulin resistance?
- chronic insulin exposure
- obesity
- excess cortisol
- Excess GH
- Pregnancy
- polycystic ovarian syndrome
- hemochromatosis
- genetic causes of obesity
What are reasons for progression to IDDM from type 2?
hyperglycemia and hyperlipidemia provide constant influx of nutrients into pancreatic B cells. –> nutrient toxicity impairs b cell secretion over time
What is a normal sign for the oral glucose/insulin tolerance test?
2 ours post-prandial level should be back to normal
what is the result for DM on the oral glucose/insulin tolerance test?
glucose does not return to normal for 4-6 hours
what is the result for DMI on the oral glucose/insulin tolerance test?
insulin low or undetectable
what is the result for DMII on the oral glucose/insulin tolerance test?
insulin high in early stage or low in late stage
What is an insulinoma?
hypersecretion of insulin from tumor of beta cells
-10-15% malignant
What can an untreated insulinoma lead to?
insulin shock due to hypoglycemia
