Noble & Sillence Diurnal rhythm and effect of feeding..2013

Noble GK, Sillence MN
Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse
Equine Veterinary Journal Vol. 45, Issue 6, p 745-750, November 2013

Introduction:
Insulin lowers blood glucose directly.
Serum insulin concentrations are affected by feeding.
Prolonged hyperinsulinaemia causes laminitis in horses and ponies with no history of laminitis or insulin resistance.
Excess body fat leads to an insulin-refractory state, which limits the uptake and utilisation of glucose by muscle.
Insulin stimulates glucose metabolism in adipose tissue leading to lipogenesis (increased fat deposit), therefore excess insulin in an obese horse leads to increased fat deposition, undermining attempted weight loss.
Growth hormone (GH) stimulations the production of IGF-1.  Chronic use of GH has lead to insulin resistance in some species.
GH stimulates beta cell proliferation, insulin gene expression, insulin synthesis and secretion.
Could GH cause insulin resistance, hyperinsulinaemia and laminitis?
Previous research has found that daily exercise leads to increased insulin sensitivity (Freestone et al. 1992, Powell et al. 2002).

The research:
12 healthy geldings averaging 460 kg aged 2 - 13 yrs in Australia were fed 3 kg oats, 2 kg wheaten chaff, 3 kg lucerne chaff, 3 kg oaten hay (11 kg total), salt and calcium carbonate, divided equally into 2 feeds and fed at 7.30 am and 4.00 pm.  (This is a lot of feed in one meal, high glucose from 1.5 kg oats per meal - analysis not given).  15.5 hrs between 4 pm and 7.30 am feed, 8.5 hrs between 7.30 am and 4 pm feed.  The horses were not exercised during this time, were presumably kept in stalls with a 12 hour light/dark cycle, were in "paddock condition", had 5 days to acclimatize before the study began.

All horses then had 3 weeks of increasing exercise on a treadmill, then were split into 2 groups, one group given GH, for 21 days, with continued exercise.

These horses in previous research had cortisol concentrations of
49.2 +/- 13.6 nmol/l midnight nadir
144.2 +/- 27.2 nmol/l 7.30 am zenith.
Cortisol secretion appears to have a diurnal pattern but this can be lost when horses' management is changed (and they are presumably stressed).

Insulin was tested every 30 minutes for 24 hours and peaked at 9.30 am 2 hours after the morning feed - max. 577.1 +/- 108.3 pmol/l, then again at 5.30 pm 1.5 hours after the afternoon feed - max 342.4 +/- 75.7 pmol/l.  The peak post-meal insulin concentrations were reached within 2 hours of feeding.
Insulin was lowest between midnight and 7.30 am when the horses were fed - this was during the longest period without feed.
Insulin was considered to not show a diurnal pattern, and to be related to feeding.  However, the insulin peak was much greater after the morning meal, perhaps because of the longer fast since the previous meal (15.5 hrs v 8.5 hrs), perhaps because of the "dawn phenomenon" (an early morning increase in insulin secretion seen in humans perhaps due to catecholamine or GH secretion), or perhaps (this is not mentioned) linked to the increased cortisol concentrations at 7.30 am.

Exercise had no effect on insulin concentrations measured at 7.30 am, before feeding, exercise or GH administration.  (However, it was hardly likely to - insulin was tested at the time of day when the lowest concentrations had been found, and many samples were below the lowest reading.  Testing insulin after the horses were fed would have been much more interesting).

GH administration at 5 pm increased insulin concentrations at 7.30 am the following day - insulin concentrations in the GH treated group varied considerably between horses and were erratic.  When GH administration was stopped, resting insulin returned to normal by the following day - the insulin resistant effects of GH appear to be short lived.  GH administration caused increased IGF-1 concentrations.  Exercise appeared to have no effect on reducing GH induced hyperinsulinaemia (although there was no non-exercised control group - this conclusion was based on other research in non-exercised horses (de Graaf-Roelfsema et al. 2005).

Conclusions: daily GH administration led to increased insulin concentrations which were not offset by daily exercise.  GH could therefore be detrimental to horses with existing hyperinsulinaemia due to the risk of laminitis.