Acromegaly produces a lean and well muscled diabetic

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TLDR: Growth hormone causes lipolysis, makes you slim, preserves muscle mass and makes you diabetic. Blocking the acute lipolysis of exogenous growth hormone exposure (acipimox again) stops the insulin resistance developing. The rest of the post is just me musing on clinical acromegaly, probably not interesting to most.
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A follow-on to the paper using intermittent hypoxia to induce weight loss combined with glucose intolerance is to look at a similar effect from growth hormone. Growth hormone excess, amongst many actions, causes fat loss, muscle gain and diabetes.

There is pretty convincing evidence that the glucose intolerance is due to the rise in free fatty acids induced by the weight loss. In the short term this can be very effectively blocked by, guess what, acipimox of course. This paper makes the point rather well:

Inhibition of lipolysis during acute GH exposure increases insulin sensitivity in previously untreated GH-deficient adults

I'd picked that paper up while I'd been been reading about acipimox and then I'd heard a completely unrelated snippet of great interest about pancreatic amyloid in acromegalic cats.

Ordinary (non acromegalic) diabetic cats frequently have amyloid accumulation within their islets. It's thought that amylin is co-secreted with insulin and forms precipitates of amyloid, if enough is co-secreted. Amyloid is also common in the pancreas of non diabetic elderly cats but this clearly begs the question of what you mean by "not diabetic". That's another line of thought for anyone who has read Kraft on diabetes in-situ.

Anyway, the rumour I have heard is that acromegalic cats, diabetic or not, have no amyloid in/around their beta cells.

That's very interesting. They're often very diabetic...

Now, clinically, we don't measure growth hormone to diagnose acromegaly. We measure the ILGF-1 produced by the liver under the influence of GH. The question to me is: Does ILGF-1 act as an insulin mimetic under conditions of high GH? Are the islets of acromegalic cats free of amyloid because they are not needing to secrete so much insulin to develop those co-secreted amylin precipitates? Can ILGF-1 "side step" the insulin resistance caused by the elevated FFAs induced by GH excess? Or anything else?

Possibly.

People with defective insulin receptors, insulin resistance A (the mild form) or Leprachaumism (the severe form) are diabetic and non-responsive to exogenous insulin. Genetically broken receptors don't work very well. The same applies to people with Berardinelli–Seip syndrome but here the intense insulin resistance is caused by elevated free fatty acids and their intracellular derivatives following on from the lipodystrophy (this is much the same as the insulin resistance following weight gain from acipimox noted after exposure non-intermittent hypoxia plus acipimox in the last post, where exogenous insulin did nothing to blood glucose).

Each of these severe insulin resistance syndromes respond to exogenous ILGF-1 with a sustained fall in blood glucose levels.

Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes


If ILGF -1 is effective in Berardinelli–Seip syndrome I see no reason why it shouldn't be effective at side stepping the FFAs of acromegaly. It won't produce normoglycaemia as it is tonically present, so doesn't respond to food intake (a bit like a basal exogenous insulin). But it does spare the pancreas this basal function so it can do its best to cover meals, working against the FFAs of acromegally...

Peter