Why does IGF lead to hyperglycemia

[sanj238]

Someone asked this in 2008 but its still hard to understand.

IGF causes hyperglycemia yet it behaves like insulin. GH causes gluconeogenesis and glucose release yet it is diabetogenic and to top it off GH test is via insulin induced hypoglycemic test. Whats going on?

GH- iGF- causes increased glucose release? Then how does IGF behave like insulin? I get that u give the test- because transient hypoglycemia should result in increased glucose via GH and if GH def. then no increase but then why would a hypgerglycemic IGF also behave like insulin (hypoglycemic) does it have to do with stages of IGF and tolerance?

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[Transposony]

This is my understanding on this topic:

GH has two kind of actions:

1. Direct:

a) Diabetogenic by decreased glucose uptake into cells (it increases glucose levels despite an insulin increase by inducing insulin resistance in peripheral tissues)
b) Lipolysis
c) Production of IGF from Liver

Indirect (via IGF):
a) Increased Protein synthesis (Growth).

Now IGF which is structurally similar to proinsulin acts by binding to receptors (receptor tyrosine kinase).
However, it's affinity to insulin receptor is 100 times less than that of Insulin and it's levels are controlled by six types of binding proteins (IGFBPs).
Therefore, IGF has less effect on reducing Glucose levels despite acting as insulin (a weak Insulin like action) than GH which causes increase in Glucose by various mechanisms (Gluconeogenesis, Decreased Glucose uptake aka Insulin resistance).

It appears that GH (directly & Indirectly) makes sure that AAs are exclusively used for Protein synthesis by maintaining (high) glucose levels and FFAs (Lipolysis) to be used for energy production.

Hope this helps.

 

[ulikedaggers]

So IGF-1 basically leads to insulin resistance while also stimulating anabolic processes via GH = double f*cked hyperglycemia?

 

[Transposony]

So IGF-1 basically leads to insulin resistance while also stimulating anabolic processes via GH = double f*cked hyperglycemia?

No.
GH leads to insulin resistance by it's direct action..
IGF-1 (being structurally similar to Proinsulin) is not very effective in countering (GH's diabetogenic effect) being 100 times less effective than Insulin itself.

In other words, IGF does not cause insulin resistance or hyperglycemia but does a poor job of countering it. Since IGF(the pupil) production is induced by GH(the master), it makes sense that IGF cannot completely counter GH's effect (simply put).

Also, Insulin itself promotes growth. So, it appears that IGF's main role here is trophic.

IOW's it's main job being trophic but does a side job as a sub for Insulin.