Dukes' Ch. 47: Disorders of Carbohydrate and Fat Metabolism Flashcards
Which hormones stimulate lipolysis?
epinephrine, growth hormone, glucagon, glucocorticoids
Which hormones control muscle protein turnover/
Glucocorticoids increase catabolism; growth hormone and insulin promote anabolism.
(Note that growth hormone is only anabolic when insulin is present. Otherwise no effect.)
How does muscle protein contribute to glucose production?
During the postabsorptive phase, muscle proteins are degraded under the influence of glucocorticoids and release amino acids to the blood, which are taken up by the liver and used for gluconeogenesis.
How does muscle glycogen contribute to blood glucose concentration?
Under influence of epinephrine, muscle glycogen is broken down to glucose 6-phosphate.
Muscle lacks the enzymes necessary to metabolize glycogen all the way to glucose so the glucose 6-phosphate is used to produce pyruvate and lactate, which are released to the blood.
The liver then converts these to glucose.
Why might glucagon administration be a good idea for treating the cow with ketosis?
Why might is be a bad idea?
At low doses it appears able to stimulate gluconeogenesis pathways in the liver.
This could help improve the glucose status of the cow.
However, at higher doses or for prolonged periods the glucagon will stimulate lipolysis, which may tax the liver’s ability to oxidize fatty acids, contributing to ketone production.
Current treatment of cows with ketosis generally includes intravenous administration of a large amount of glucose solution in a short time.
(A) Why might it be a good idea to give the dairy cow with ketosis an injection of insulin at the same time?
(B) Why might this be a bad idea?
(C) Is propylene glycol a good idea?
(D) Is injecting dexamethasone (a synthetic glucocorticoid) a good idea?
(A) The cow’s tissues take up more of the injected glucose so it is not lost to the urine.
(B) You could overdose the cow with insulin and drive blood glucose too low. Also she is able to make her own
insulin, so is it really necessary?
(C) Probably a good idea to supply the cow with glucose precursors orally as she usually is not eating on her own when she has ketosis.
(D) It could stimulate gluconeogenesis, which would be helpful. It will also reduce milk production, which helps improve energy balance. Its major downside is possible suppression of the immune system.
Pregnancy toxemia in ewes is sometimes treated by inducing parturition in the ewe.
Why might this be a good idea?
It removes the fetal drain of glucose, which can improve the energy balance of the ewe allowing her to regain control of her blood glucose.
(A) What is the “Somogyi overswing”?
(B) Why is it important for you to know this?
(A) A phenomenon that can occur when an animal is given a large dose of insulin. Instead of driving blood glucose just to normal limits, the large dose can actually drive blood glucose below normal levels in several hours. This then stimulates the body to produce epinephrine, glucagon, and growth hormone to increase blood glucose. The gluconeogenic mechanisms are activated about the time that the initial insulin dose has worn off. As a result blood glucose rises above the renal threshold for glucose and there will be
glucose in the urine.
(B) Most animal clinicians utilize the appearance
of glucose in urine as an index of the success of their treatment of the diabetic patient. Ordinarily, the appearance of glucose in the urine might suggest the animal has not been given enough insulin. However, it is also possible that the animal has been overdosed with insulin. Thus the presence of urine glucose must be interpreted
cautiously.
Why do holstein cows maintained on pasture in early lactation often develop ketosis?
Fermentation of grass diets often fails to provide enough three-carbon propionate units to allow high-producing cows (most Holsteins today) to make the glucose needed to produce milk lactose.
One might assume they would just make less milk.
However, the dairy
breeds will often make milk, requiring energy beyond what the diet will supply, until they become clinically ill from ketone body formation.
The typical dairy cow loses 45–68 kg body weight in early lactation as she utilizes body reserves to help supply the energy needed for milk production.
(A) How will she make the needed glucose?
(B) What role is body fat playing in this process?
(A) From amino acids liberated from muscle protein and lactate liberated from muscle tissue.
(B) It liberates fatty acids and glycerol. The glycerol can be used to make glucose directly in the liver. Peripheral tissues could use the fatty acids as an energy source to spare the blood glucose for other uses.
In human medicine, many people with adult‐onset diabetes are successfully treated with the oral hypoglycemic drug tolbutamide.
Why does this not seem to be a common option in veterinary medicine?
Tolbutamide can stimulate the remaining pancreatic islet β cells to increase production of insulin to overcome tissue resistance.
By the time the diabetes is recognized in most canine or feline patients the condition has progressed to the point that the β cells have undergone exhaustion and will not respond to insulin secretagogues.
It is Christmas Day, with snow on the ground, and you are on call again!
The mother of a newborn litter of retriever pups is brought to you because she will not eat and is running a fever.
You diagnose mastitis. You are worried about the pups housed out in the garage.
Why?
The lack of milk production by the mother means the pups may not be getting any nourishment.
Unfortunately, the pup has little body fat and little stored glycogen reserves to draw on during the postabsorptive phase.
The cold weather increases the energy requirement of the pup.
Without a steady supply of glucose from the diet the pups are in danger of developing hypoglycemia and hypothermia.
Describe the major role of the liver in the absorptive and in the postabsorptive phase of metabolism.
<i>Absorptive phase</i>: Produces glycogen, and produces triglycerides (combining glycerol from the absorbed glucose with fatty acids from the diet or produced de novo) and packages them into lipoproteins, made from absorbed amino acids, for use by peripheral tissues. Excess amino acids can be converted to fatty acids.
<i>Postabsorptive phase</i>: Breaks down glycogen to release glucose to blood, gluconeogenesis from amino acids, glycerol, or other three-carbon compounds like propionate, pyruvate, or lactate from muscle. Oxidation of fatty acids to fuel liver functions. Conversion of some fatty acids to ketones for export to peripheral tissues.
Describe the major role of muscle in the absorptive and in the postabsorptive phase of metabolism.
<i>Absorptive phase</i>: Stores glucose as muscle glycogen, builds muscle proteins from amino acids, stores some extra glucose (or glucose from excess amino acids) as fat.
<i>Postabsorptive phase</i>: Breaks down glycogen to release lactate to blood. Catabolism of muscle protein to provide liver with gluconeogenic precursors.
Describe the major role of adipose tissue in the absorptive and in the postabsorptive phase of metabolism.
<i>Absorptive phase</i>: Takes up glucose to form fatty acids and triglycerides for storage as fat, uses fatty acids and triglycerides incorporated into chylomicrons (diet) or lipoproteins (packaged in liver) for storage as fat.
<i>Postabsorptive phase</i>: Releases fatty acids (alternative to glucose as energy source for some tissues) and glycerol (gluconeogenic) into circulation.
