LEC 5 - Drugs Effecting Glucose Metabolism Flashcards by Raegan Chambers

What cell type in the pancreas is responsible for glucose regulation?

Pancreatic islet

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What cell type in the pancreas is responsible for the release of digestive enzymes?

Pancreatic acini

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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

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What are the two pathways in the liver that allow for glucose to enter blood when levels are low?

Glycogenolysis

– and –

Gluconeogenesis

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What are the glucose releasing hormones?

Glucagon

Catecholamines

Cortisol

Growth hormones

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What cell types releases insulin?

Beta cells

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What cell types release glucagon?

Alpha cells

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How do the beta cells know when to release insulin?

Glucose through GLUT

Stimulates Na channels and Ca channels

Cell depolarizes

Insulin released

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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

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What are the signs of diabetes mellitus?

PU/PD

Weight loss even iwth polyphagia

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What do dogs get with chronic DM?

Cataracts

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What do cats get with chronic DM?

Neuropathy

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What is seen in clinical chemistry with DM?

Blood glucose higher than normal

Glucouria

Increased fructosamine levels

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Why do you see glucouria with DM?

Blood glucose higher than the capacity that the kidney can shuttle back into the ody

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What type of DM is most common in dogs?

Type 1

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What is the progonosis of a dog with type 1 DM?

Surive 2 to 3 years

Cataracts within 5 to 6 months

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What causes type 1 DM?

Loss of functioning beta cells

(90% have to be lost for symptoms to be seen)

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What are the etiologies of type 1 DM?

Autoimmune

Genetics

Acute, severe pancreatitis

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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

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Common causes of Type 2 DM?

Obesity

Concurrent dz

Chronic inflammation

Renal/Hepatic/Cardiac insuffiency

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What can cause severe peristant insulin resistance?

Diestrus induced increase in GH

Cushing’s disease

Diabetogenic drugs

Acromegaly

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What are the drugs that can cause insulin resistance?

Progestin

Glucocorticoids

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How can dogs get type 2 DM?

Have several of the predisposing causes

Can occur in Type 1

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What is the irreverisble part of insulin resistance?

Deposition of toxinc amyloid in islets

Reduced insulin secretion

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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?

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