LEC 5 - Drugs Effecting Glucose Metabolism Flashcards
What cell type in the pancreas is responsible for glucose regulation?
Pancreatic islet
What cell type in the pancreas is responsible for the release of digestive enzymes?
Pancreatic acini
How does the liver play a role in glucose regulation?
Stores glucose as glycogen when glucose is high
Delivers glucose to plasma when levels drop
What are the two pathways in the liver that allow for glucose to enter blood when levels are low?
Glycogenolysis
– and –
Gluconeogenesis
What are the glucose releasing hormones?
Glucagon
Catecholamines
Cortisol
Growth hormones
What cell types releases insulin?
Beta cells
What cell types release glucagon?
Alpha cells
How do the beta cells know when to release insulin?
Glucose through GLUT
Stimulates Na channels and Ca channels
Cell depolarizes
Insulin released
How do the alpha cells know to release glucagon?
No glucose through GLUT channel
Allow for Na and Ca channesl to be placed
Glucose is inhibitory in this cell type
What are the signs of diabetes mellitus?
PU/PD
Weight loss even iwth polyphagia
What do dogs get with chronic DM?
Cataracts
What do cats get with chronic DM?
Neuropathy
What is seen in clinical chemistry with DM?
Blood glucose higher than normal
Glucouria
Increased fructosamine levels
Why do you see glucouria with DM?
Blood glucose higher than the capacity that the kidney can shuttle back into the ody
What type of DM is most common in dogs?
Type 1
What is the progonosis of a dog with type 1 DM?
Surive 2 to 3 years
Cataracts within 5 to 6 months
What causes type 1 DM?
Loss of functioning beta cells
(90% have to be lost for symptoms to be seen)
What are the etiologies of type 1 DM?
Autoimmune
Genetics
Acute, severe pancreatitis
What is the cause of Type 2 DM?
Acquired resistance of tissues to insuling
Problems binding to receptor
Problems with function of the receptor
Problems with downstream signaling
Common causes of Type 2 DM?
Obesity
Concurrent dz
Chronic inflammation
Renal/Hepatic/Cardiac insuffiency
What can cause severe peristant insulin resistance?
Diestrus induced increase in GH
Cushing’s disease
Diabetogenic drugs
Acromegaly
What are the drugs that can cause insulin resistance?
Progestin
Glucocorticoids
How can dogs get type 2 DM?
Have several of the predisposing causes
Can occur in Type 1
What is the irreverisble part of insulin resistance?
Deposition of toxinc amyloid in islets
Reduced insulin secretion
What is the reversible part of insulin resistance?
High blood glucose
leads to gluco/lipotoxicity
What is remission in cats associated with?
Insulin choice
low carb diet
strict monitoring
What does remission in a cat require?
Presence of functioning beta cells
What type of DM do horses tend to get?
Type 2
What are the treatment goals of DM?
Eliminate clinical signs
Prevent complications
Good quality of life
NOT TO MAINTAIN GLUCOSE IN NORMAL RANGE
What are the classes of insulin?
Short acting
Intermeidate acting
Long acting
What are the characteristics of long acting insulin?
laast 12 to 24 hours
What are the characteristics of intermediate acting insulins?
8 to 18 hours
Used for maintence
Admin SC
Give with meal
What are the characterisitics of short acting insulin?
1 to 4 hours
given iV
Used in emergencies
What is insulin metabolized by?
liver and kidney
What are adverse reactions to insulin?
Hypoglycemia
Hyperglycemia
Local/systemic immune reactions
What is porcine zinc suspension type?
Intermediate
What are the characteristics of porcine insulin zinc suspension?
Two peaks of activity - has long and short action
zinc crystals slow absorption
Why is porcine insulin handled by dogs better?
Same AA sequence
What type of insulin is neutral protamine hagedorn insulin?
Intermediate
What are the characteristics of neutral protamine hagedorn insulin?
Protamine slows absorption
Single peak of activity
Human recombinant
What type of insulin is protamin zinc insulin?
Long acting
What is the composition of protamine zinc insulin?
90% beef - 10% pork
immune reaction seen in dogs
which leads to insulin resistance
What type of insulin is glargine insulin?
Long acting
What is the problem with glargine insulin
High concentration so easy to overdose
Cn precipitate when given
What is great about glargine insulin?
Can cause remission in cats
What type of insulin is determir insulin?
Long action
What is so good about detemir insulin?
Allows for remission in cats
With no precipitation
Increased plasma protein binding = decreased elimination
What is the polypol pathway responsible for/
Cataracts
Neuropathy
What is the polypol pathway?
Glucose > Sorbitol
Sorbitol causes glycationof protein NH2 groups
What can sorbitol glycation be detected by?
Fructosamine
A1C
What does fructosamine detect?
Glycated albulmin
What does A1C detect?
Glycated hemoglobin
Which sorbitol test is done for animals?
Fructosamine
When should insulin resistance be considered?
Glucose control is erratic
Insulinn doses constantly changing
Glucose levels < 300
Can’t get them below that
What can be fatal when adjusting insulin doses?
Hypoglycemia
What causes DKA/
Uncontrolled hyperglycemia
Chronic ketone body formation by liver
Ketone body = strong acid
Severe metabolic acidosis
What are the signs of DKA?
Lethargy / depression / coma
Dehydration
Muscle wasting
Heptaomegaly
Plantigrade stance in cats
What is the order of treatment for DKA?
Correct dehydration
Admin short acting insulin
Correct electrolyte imbalances
Correct acidosis
What electrolyte imbalance is most common with DKA?
Hypokalemia
How does insulin help with hypokalemia?
Increase activity of Na-K ATPase in cell membrane leading to cellular uptake of potatssium
When is glupizide given?
Possible alternative to someone who doesnt want to give injections
Cat on well maintained low dose of insulin
Where does glipizide act?
K channel in beta cell
How is glipizide handled in the body?
PO
What are the adverse reactions seen with glipizide
Promotes formation of toxic amylin fibers = death of beta cells
Reduce changes of remission
Hepatotoxic
Hypoglycemia
How does metaformin work?
Reduces glucose output by the liver
increase glucose uptake
inhibit gluconeogenenesis by opposing glucagon signals
When is metaformin used?
Type 2 DM
Cats
What are the adverse reactions to metaformin?
Vomiting, lethargy, weight loss
Overdose = lactic acidosis
do not use with cats in renal dz
What is the use of kinostat?
Prevents cataracts in dogs
How does kinostat work?
Inhibits aldose reductase
Stops glucose to sorbitol in eye
What is the treatment for hypoglycemia?
Karo sryup on gums ASAP
IV fluids with dextrose in hospital once there
What is octreotide used for?
Insulinomas in ferrets and dogs
How does octreotide work?
Inhbits insulin gene expression
What is diazoxide used for?
Insulinomas in dogs and ferrets
How does diazoxide work?
Increased potassium permeability in beta cells
why is diazoxide a bad choice for most owners?
1/2 life = 5 hours
have to give 4 times a day