Chapter 10 endocrine system - pancreatic hormones Flashcards
Insulin
- produced by pancreatic islet beta cells
Alpha cells
- Comprise approximately 20% of the islet cells
- They secrete glucagon, which increases blood glucose concentrations between meals.
Beta cells
- Comprise approximately 65% of the islet cells
- They secrete insulin, which lowers blood glucose concentrations after a meal.
Delta cells
- Comprise approximately 10% of the islet cells
- Secrete somatostatin, which inhibits insulin and glucagon secretion to moderate their effects on blood glucose concentrations.
F cells
- Are rare
- They secrete pancreatic polypeptides, whose specific functions are uncertain.
Diabetes mellitus
- insulin dependent diabetes mellitus (IDDM; type 1)
- d/t absolute deficiency of insulin which typically develops by age 15
effects
* weight loss
* hyperglycemia
* ketoacidosis
* artheroscleorsis
* retinal damage
* kidney failure
d/t damaged or destroeyd pancreatic islet beta cells ===> oral hypoglycemics cannot induce insulin release => thus require insulin injections
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Noninsulin dependent diabetes mellitus (NIDDM; typeII)
* d/t decreased release of insulin or decreased response of tissue to insulin (such as d/t decreased # of insulin receptor) => result in hyperglycemia but not ketoacidosis
Treatment
* diet + exercise
* oral hypoglycemics fail then insulin!
insulin replacement
- repeated injection @ same site may result in atrophy or hyperplasia at injection site
- human insulin preferred to insulin prepared from animals b/c it is less antigenic (porcine insulin differs from human insulin by one amino acid (terminal argenine))
- typical dosing regimen — regular humulin with either lente or NPH 2-3 x per day before meals
toxicity
* hypoglycemia —
1) weakness/dizziness
2) hunger
3) sweating
4) tachycardia
5) anxiety/tremor
6) headache
7) mental disturbancecs + visual disturbances
* above are caused by hypoglycemic release of epinephrine (since this NT causes glyconeolysis, gluconeogenesis and lipolysis and inhibits insulin secretion) + while rest of sx are d/t brain being straved of energy
- hypokalemia
1) insulin drive K+ from serum into cells
2) often encountered w/ ketoacidosis whwen insulin therapy is started
effects of above ——– - cardiac arrhythmias
- neuromusular disturbances
insulin drug interactions
1) agents that inc blood glucose — antipsychotics, diazoxide (Vasodilator - It can treat low blood sugar (hypoglycemia) caused by certain cancers, surgery, and other conditions when taken orally.), adrenergic antagonists (also dec insulin release) + thyroid supplements
2) agents that dec blood glucose — alcohol, weight reducing agents and catecholamine depleting agents
oral hypoglycemic drugs
- pts that fail dietary control (w/ type II) require oral hypoglycemic agents
- sulfonylureas — stimulate insulin sec via pancreatic beta cells and inc sensitivity of tissues to actions of insulin
- newer generations of oral hypoglycemics —
1) reduce post prandial sugar levels (during or relating to the period after dinner or lunch.) or inc sensitivity of target tissues to insulin (nonsulfonylureas less likely to cause hypoglycemia)
actions of insulin
MUSCLE
1) inc glucose transport into celll
2) glycogenesis
3) inc protein and triglyceride synthesis
LIVER
1) inc glucose transport into cells
2) inc glycogenesis
3) inc glucose utilization in kreb cycle
4) inc protein synthesis
ADIPOSE
1) inc glucose transport into cell
2) inc glycogeneis
3) inc triglyceride synthesis
Regular insulin (a)
prompt insulin zinc suspension (b)
lispro insulin solution (c)
insulin glulisine (d)
rapid acting
a
* onset - 0.5-1 hr
* duration - 5-8 hrs
* humulin R, novolin R, regular Iletin II, velosulin
b
* onset - 1-2 hr
* duration 12-16
c
* onset - 0.25 hr
* duration 6-8 hour
* humalog, ademlog, basaglar
d
* onset - 0.5-1.5 hr
* duration- 1-2.5 hr
* adipra
isophane insuline suspension (a)
insulin zinc suspension (b)
insulin glargine (c)
intermediate acting
a
* onset - 1-2
* duration -24-28
* humulin N, novolin N
b
* onset - 1-3
* duration - 24-28
* humulin L, lente insulin, lente Iletin I + II, novolin L
c
* onset - 1 hr
* duration - 24 hr
* lantus, toujeo
extended insulin zinc suspension (a)
insulin degludec (ultralong) (b)
long acting
a
* onset 4-8 hours
* duration >36 hours
* humulin U ultralente
b
* onset - 0.5-1.5
* duration - >42
* tresiba
isophane insulin suspension and insulin injetion
combination
- onset - 0.25-1
- duration - 24 hrs
- novolin 70/30, humulin 70/30, humulin 50/50
tolbutamide (orinase)
tolazamide (tolinase)
chlorpropamide (diabinese)
glipizide (glucotrol)
glyburide (micronase, diabeta)
glimepiride (amaryl)
sulfonylureas
- stimulate insulin secretion by pancreatic beta cells + inc sens of tissues to insulin
effect
hypoglycemia
* patient who develop hypoglycemia while taking chlorpropamidae must be monitored for 3-5 days d/t long half life (60-90 hrs)
* tolbutamide — increased risk of cardiotoxicity when tolbutamide used for more than 5 years
metformin (glucophage)
nonsulfonylureas
- reduce intestinal upatake and hepatic production of glucose
- inc sens to insulin in tissues
- generally does not cause hypoglycemia…
- may be synergistically with sulfonylureas
effects
* rarely cause lactic acidosis => can be fatal
* more GI side effects
miglitol (glyset)
acarbose (precose)
nonsulfonylureas
- alpha glucoside inhibotr slows carbohydration digestion resulting in lower serum glucse levels after meals
- can be used with sulfonylureas
effect
* hypoglycemia happens when used by itself
* flatulence, diarrhea, abdominal pain = frequent
rosiglitazone (avandia)
pioglitazone (actos)
nonsulfonylureas
enhance response of target cell (liver, muscle) to endogenous insulin — mech includes activating nuclear receptors that increase transcription of glucose control genes
* b/c require endogenous insulin DO NOT GIVE WITH TYPE 1 or diabetic ketoacidosis
- monitor LFTs
- d/c drug if LFTs are greater than 3 times normal
- may inc incidence of CHF and MI
repaglinide (prandin)
nonsulfonylureas
- blocks K+ channels in pancreatic beta cells, causing depolarization, ca++ influx, and ultimately insulin secretion
- result — dec glucose levels via mech that requires intact beta cells
- used alone or with metformin for type 2 that is diet refractory
nateglindine (starlix)
nonsulfonylureas
- stimulate insulin secretion
