Equine Endocrinopathies

Question 1

How is insulin synthesised

Answer 1

initially preproinsulin from beta-cells
signal peptide is removed to leave proinsulin
C-peptide is removed to leave insulin (made up of A and B peptides)

Question 2

What does insulin do ? ( 3x actions)

Answer 2

1. glucose “gatekeeper”
   - inspires liver, fat and resting muscle (“insulin sensitive tissues”) to take up glucose
2. metabolic effects
   - stimulates glycogen synthesis
   - stimulates FA uptake and triglyceride synthesis
   - stimulates cellular AA uptake
   ( in turn, inhibits glycogenolysis, gluconeogenesis, lipolysis and proteolysis)
3. other effects
   - increases K+ uptake
   - increases Na+ resorption in the kidney
   - stimulates gastric acid secretion
   - vascular effects

Question 3

Define obesity

Answer 3

excessive adiposity to a degree that results in a negative health effect

Question 4

How do we measure obesity ?

Answer 4

in the lab with tests or in practice by weighing body mass and calculating the BMI (weight/height^2).

also BCS and cresty neck score in horses

Question 5

Define bioimpedance

Answer 5

a weak electric current flows through the body and the voltage is measured to calculate impedance (resistance and reactance)

this works because lean tissue is a good conductor where fat is a poor conductor

Question 6

Define hydrometry

Answer 6

give a set dose of deuterium oxide (D2O) and measure the saliva
total body water = dose / concentration in saliva
body fat % = 100-(%TBW/0.732)

Question 7

How can insulin resistance be a survival advantage to individuals in a harsh/variable environment ?

Answer 7

conservation of glucose for vital organs (CNS, heart, etc…)
mobilisation of energy stores

Question 8

Define laminitis

Answer 8

elongation of secondary epidermal lamellae, primarily due to stretching but also partially due to an increase in cell proliferation.

Question 9

How is insulin involved in laminitis ?

Answer 9

insulin activates 2 metabolic pathways ..
1. PI3 kinase (metabolic and vasodilation)
2. MAP kinase (growth and vasoconstriction)

Question 10

What happens in the event of insulin resistance (laminitis wise)

Answer 10

PI3 kinase pathway is affected, and the compensatory mechanism overstimulates the MAP kinase pathway.

it may lead to dysregulation of lamellar epithelial cell growth, but these cells do not have insulin receptors, so it cannot be the main cause of laminitis.

Question 11

How are IGF-1 and insulin related, and how does this affect laminitis ?

Answer 11

IGF-1 is synthesised by the liver and mediates GH effects, stimulating cell growth and regeneration.

lamellar epithelial cells do not have insulin receptors, but they do have IGF-1 receptors, which can be stimulated by high levels of insulin (-> proliferation of lamellar epithelial cells)

Question 12

Define equine metabolic syndrome

Answer 12

a collection of risk factors for endocrinopathic laminitis, including insulin dysregulation, obesity CV changes and adipose dysregulation.

Question 13

What are the CS of EMS

Answer 13

susceptibility to laminitis
obesity (general and/or regional)

Question 14

What are the metabolic features of EMS ?

Answer 14

insulin dysregulation
obesity, inactivity and diet

Question 15

How do you diagnose endocrinopathic laminitis ?

Answer 15

insulin dysregulation can be tested for in blood concentrations (especially postprandially). You may also see high triglyceride levels

Question 16

Define PPID

Answer 16

pituitary pars intermedia dysfunction

Question 17

What is the primary causal event of PPID ?

Answer 17

oxidative damage to inhibitory dopaminergic neurones, which releases the pars intermedia from inhibition and leads to excessive GH and other hormone release

Question 18

Describe PPID histopathologic grading system

Answer 18

Grade 1 = normal
Grade 2 = mild hypertrophy / hyperplasia, may be normal if older animal
Grade 3 = marked hypertrophy / hyperplasia (mild PPID?)
Grade 4 = ^ + microadenoma (moderate PPID)
Grade 5 = ^ + macroadenoma (marked PPID)

Question 19

What are the CS of PPID

Answer 19

susceptibility to laminitis
abnormal hair growth
excessive drinking and urination
susceptibility to infections
muscle catabolism
(we don’t know what causes these!)

Question 20

How do we diagnose PPID ?

Answer 20

blood test :
high POMC-derived peptides especially ACTH
high insulin with normal glucose

common also to inject insulin and measure the effect it has on glucose levels

Question 21

What are the 2 major lipoproteins ?

Answer 21

chylomicrons (large, rich in triglyceride, transport exogenous lipid into tissues, dietary)
VLDLs (synthesised by the liver, 2nd largest, 2nd richest, transport endogenous lipid to tissues, adipose)

Question 22

What happens during fasting to lipid metabolism ?

Answer 22

1. triglycerides in fat stores are broken down into glycerol and 3 NEFAs, which are released into the bloodstream
2. liver takes up NEFAs from the blood and uses them for energy
   OR 2. NEFA converted into triglycerides, ATP and ketones
3. triglycerides incorporated into VLDL, which is secreted into plasma
4. tissues extract NEFAs from the VLDLs
5. all remnants return to the liver

Question 23

Define hyperlipaemia in horses and give CS and causes

Answer 23

plasma TG >5mmol/L

CS :
- sick
- inappetant
- plasma is opaque

causes :
- pregnancy/lactation/poor diet
- secondary following disease
- insulin resistance

Question 24

Define hypertriglyceridaemia

Answer 24

plasma TG level greater than normal, but plasma is normal and the animal is not sick or inappetant

Question 25

Define seasonal pasture myopathy

Answer 25

an acute, non-exertional rhabdomyolysis syndrome affecting healthy grazing horses.
caused by hypoglycin A from sycamore seeds, which blocks the entry of NEFAs into mitochondria in the fasting lipid breakdown normal process

Question 26

Define ketosis in cattle

Answer 26

beta-hydroxybutyrate > 1.2mmol/L
Type 1 = peak lactation, due to low glucose availability
Type 2 = post-partum, glucose is more available but low CPT-1 activity

Question 27

Define hepatic lipidosis in cats

Answer 27

similar to type 2 ketosis in cows, most common cause of cat liver disease.
affects overweight cats due to insulin resistance

Question 28

How to we manage endocrinopathic laminitis ?

Answer 28

control diet and fitness.
standard plan involves weight loss by 1 small meal a day and increased aerobic exercise

issue = do not directly change the hyperinsulinemia

Question 29

How can we aim to treat endocrinopathic laminitis ?

Answer 29

deal with laminar damage (mainly the farrier’s job)
prevent ongoing laminar insults which the foot recovers (the vet’s job, endocrine assessment to establish the cause of the laminitis and sort an appropriate management scheme for moving forwards)