Glucose & Lipid Metabolism

1. Dietary intake

2. Insulin to glucagon ratio (I:G)

(Also liver function & insulin antagonists are factors)

Regulation of blood glucose concentration is multifactorial, what are the major factors?

1. Intestinal absorption (monogastric animals)

2. Hepatic production

3. Renal production (minor contribution)

What are the sources of glucose?

Gluconeogenesis and glycogenolysis

What are the ways in which the liver produces glucose?

Gluconeogenesis

Formation of glucose from noncarbohydrate sources

Glycogenolysis

Breakdown of glycogen to produce glucose

1. Liver

2. Muscle

3. Fat

What tissues have cellular uptake of glucose stimulated by insulin via up regulation of glucose transporters to the cell surface?

1. RBCs

2. Neurons

3. Renal tubular epithelial cells

4. Pancreatic ß cells

5. Lens of the eye

Which tissues do not require insulin for glucose uptake?

Glucose disposal rate

The rate at which glucose leaves the blood stream and enters tissues is referred to as what?

Volatile substances

Fermentation in the rumen converts glucose to ________________ that are absorbed and used for energy production

A

T or F: The RI for glucose is much lower in ruminants than monogastric animals

Insulin

Primary hormone when blood glucose concentration is high

Glucagon

Hormone that prevents hypoglycemia during fasting and only exerts effects when insulin concentrations are low or when stimulated by additional hormones that oppose the actions of insulin

Constant

Actions of insulin and glucagon together are needed to maintain ___________ blood glucose concentrations

Beta cells

What cells produce insulin?

Alpha cells

What cells produce glucagon?

Delta cells

What cells produce somatostatin?

F cells

What cells produce pancreatic polypeptide?

Beta cells, which produce insulin in response to glucose levels

When portal blood enters the islets of langerhans, what does it first interact with?

A

T or F: When you give insulin SQ to a diabetic patient insulin and glucagon will not be as tightly coordinated

Hyperglycemia

Substantial loos of islet tissue (>70%) leads to _____________ due to insufficient production of insulin

Blood glucose concentration

The liver sees pancreatic hormones via the portal circulation, and responds to modulate the _________________

Ratio of insulin to glucagon

The ______________ regulates the metabolic state of the liver with regard to glucose regulation

Promotes fuel storage (stimulates glycogen production; inhibits beta oxidation of ketones, gluconeogenesis, and glycogenolysis)

What overall effect does insulin have on the liver?

Promotes fuel storage and protein synthesis

What effect does insulin have on muscle?

Promotes fat storage (stimulates storage of lipids and inhibits hormone sensitive lipase which prevents breakdown of lipids)

What effect does insulin have on adipose?

Liver

What is the target organ of glucagon?

1. Enhances glycogenolysis and gluconeogenesis (promotes glucose output by the liver)

2. Stimulates beta oxidation of fatty acids to form ketone bodies (alternative energy source)

What effects does glucagon have on the liver?

Hypoglycemia

What does glucagon protect from?

A

T or F: Glucagon is only effective when insulin is low

Liver makes more glucose, and glucose use is impaired resulting in mild/moderate hyperglycemia

What is the result of glucocorticoids?

Hyperglycemia and hyperlipidemia

Increased glucocorticoids will cause what in terms of glucose and lipids?

Adrenal cortex

What is the source of glucocorticoids?

A

T or F: Hyperadrenocorticism may lead to hyperglycemia, but the blood glucose usually does not exceed the renal threshold

Adrenal medulla

What is the source of catecholamines?

1. Increases glycogenolysis in liver and muscle

2. Inhibits insulin secretion

3. Stimulate glucagon secretion

What function does catecholamines have in energy metabolism?

Excitement hyperglycemia in cats

What is a common clinical presentation due to catecholamines?

A

T or F: Excitement hyperglycemia typically resolves quickly (within ~30 minutes)

B (you should an increase in lymphocytes)

T or F: With excitement hyperglycemia, you will see an increase in glucose but a decrease in lymphocytes on your leukogram

B

T or F: Patients with excitement hyperglycemia will also have glucosuria

Hypothalamus

What is the source of growth hormone?

Decrease peripheral use of glucose and increase hepatic glucose synthesis

What is the net effect of growth hormone?

Acromegaly (excessive growth hormone)

This disease causes marked peripheral insulin resistance and patients present as diabetes mellitus that is very hard to regulate, typically needing a very high dose of insulin

Progesterone

What induces growth hormone in dogs?

Functional pituitary adenoma

What induces growth hormone in cats?

Ovaries and uterus

What is the source of progesterone?

Increased serum progesterone concentrations can cause a preclinical diabetic to become overtly diabetic

What is the clinical effect of progesterone?

Blood glucose and cholesterol

What are the parameters of energy metabolism commonly evaluated on a general chemistry profile?

1. PU/PD (hyperglycemia)

2. Weakness, coma, change in behavior, & seizures (hypoglycemia)

What clinical signs are indicative for evaluation of the blood glucose concentration?

Hyperglycemia

PU/PD is associated with (hypoglycemia or hyperglycemia)

Hypoglycemia

Weakness, coma, change in behavior, and seizures

1. Postprandial (transient)

2. Iatrogenic

3. Increased glucose production and release

4. Peripheral insulin resistance

5. Lack of insulin

What are the 5 general causes for hyperglycemia?

Transient, persistent

Physiologic hyperglycemia is _______________ while pathologic hyperglycemia is _____________

Type 1 diabetes mellitus

Destruction of beta cells of the pancreas leads to absolute insulin deficiency

Type 1 diabetes mellitus

What is the most common form of diabetes mellitus in dogs?

1. Middle aged female dog

2. Glucosuria

3. Marked hyperglycemic

What is a typical patient for T1DM?

Type 2 diabetes mellitus

Peripheral insulin resistance leads to this

Beta cell exhaustion

In type 2 diabetes mellitus there is persistent hyperglycemia, this leads to what?

1. Obese cat

2. Marked hyperglycemia

3. Glucosuria

What is a typical patient for T2DM?

Type 2 diabetes mellitus

What is the most common form of diabetes mellitus in cats?

Chronic pancreatitis and endocrine disorders

What is a common cause for diabetes mellitus?

60

For monogastric animals, hypoglycemia is considered fasting blood glucose concentration < _________ mg/dl

1. Decreased glucose uptake from the gut

2. Decreased glucose production

3. Rapid, excessive transport from blood into cells

4. Excessive glucose utilization by cells

5. Xylitol

What are the 5 causes for hypoglycemia in monogastric animals?

Xylitol

Potent stimulator of insulin release independent of glucose concentrations and can cause hepatic failure

40

For ruminant animals, hypoglycemia is considered fasting blood glucose concentration < _________ mg/dl

1. Bovine ketosis (early lactation)

2. Pregnancy toxemia in sheep and goats

What are the 2 main causes for hypoglycemia in ruminants?

Hypoglycemia with ketosis

For bovine ketosis, what do you expect in terms of glucose/ketones?

Hypoglycemia with ketosis

For pregnancy toxemia in sheep and goats, what do you expect in terms of glucose/ketones?

Hyperglycemia and ketosis

For type 1 and 2 diabetes mellitus, what do you expect in terms of glucose/ketones?

A (~12% lower with a normal PCV)

T or F: Whole blood glucose concentration is slightly lower than plasma

B

T or F: Arterial blood glucose concentration is slightly lower than venous (~10 mg/dl) because of peripheral glucose utilization

A

T or F: For monogastric animals to get a blood glucose measurement, they should be fasted for 12 hours

B

T or F: Ruminants, like monogastric animals, need to be fasted for a blood glucose measurement

Separate serum/plasma from RBCs within 30 minutes of collection

What is important to do if you are measuring blood glucose from serum or plasma?

Sodium fluoride (gray top tube)

This tube is good for getting a blood glucose measurement because it inhibits glycolysis; however, it interferes with many assay methods

Negative

Normal urine glucose is what?

Renal threshold

The amount of glucose entering the glomerular filtrate exceeds tubular capacity for reabsorption

Serial blood glucose curve

Used to monitor diabetic animals receiving exogenous insulin

Serial blood glucose curve

Blood glucose concentration is measured approximately every 2 hours through a 10-24 hour period to assess response to insulin administration

1. Response to insulin

2. Duration of effect

3. Glucose nadir

What is measured from a serial blood glucose curve?

Glucose nadir

Low point of glucose curve

Interstitial blood glucose

Continuous glucose monitoring systems are monitoring what?

1. Monitoring hospitalized patients

2. Improve long term glycemic control

What is the purpose/use of glucose monitoring systems?

If a patient is dehydrated, hypovolemic, or in shock

What make decrease accuracy of glucose monitoring systems?

A

T or F: Glucose monitoring systems still needs to be performed in hospital mostly

Fructosamine

Any plasma protein that has an attached carbohydrate group

Blood glucose concentration is consistently high

The amount of fructosamine increases when what?

Past 1 to 2 weeks

Fructosamine indicates the average blood glucose concentration over what time span?

Albumin and lipoproteins

Fructosamine is comprised of what group of glycated proteins?

1. Hypoproteinemic

2. Hyperthyroid cats

Fructosamine will be falsely decreased in what patients?

A

T or F: For both glycosylated hemoglobin and glycoslated proteins formation is irreversible so values do not return immediately to normal when blood glucose regulation improves

Large animal

Glucose tolerance tests are mainly used in what?

Glucose tolerance test

Used to confirm glucose intolerance in animals that are hyperglycemic but do not have glucosuria

Ketone bodies

Beta oxidation of fat produces Acetyl CoA which is metabolized to what in the liver?

when carbohydrates are not available for cells and/or insulin is decreased (negative energy balance)

When are ketones formed?

1. Diabetes mellitus

2. Starvation

3. Bovine ketosis

4. Pregnancy with decreased caloric intake or heavy parasite burden

What are some causes for ketogenesis?

Metabolic acidosis

Excessive ketone production results in what?

B

T or F: It is normal to find ketones in urine through a dipstick test

Beta-hydroxybutyrate

What does the urine ketone dipstick test not detect?

Beta-hydroxybutrate

_________________ is the major ketone in domestic animals

Increased

Ketonemia causes an ____________ anion gap