The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

The GH, IGF-I Insulin axis (#17)

Aart Jan van der Lely 1
  1. Erasmus MC, Rotterdam, NETHERLANDS, Netherlands

In many instances, the GH and IGF-I levels in patients with pituitary diseases is a well-known combination of hormones that are tightly intertwined. In diabetes patients the insulin – glucose relation is the driver of treatment in which HbA1c is used as the outcome parameter. However, both in pituitary diseases in which the GH-IGF-I axis is disturbed as well in diabetes, all three hormones (GH and IGF-I and insulin) are equally important factors. To understand how they influence each other is important for proper patient care.

The physiological effects of GH versus IGF-I remain controversial. Historically, it has been difficult to isolate the individual effects of GH and IGF-I at the tissue level during physiological conditions. But the fact that GH possesses a diabetogenic or ‘anti-insulin’ activity while IGF-I (as the name implies) is similar to insulin in its actions, clearly demonstrates that physiological differences exist between the actions of the two peptide hormones. Human and other mammals are capable of prolonged fasting because they can recruit and utilize lipid stores when they exhaust readily available carbohydrates. Prolonged fasting is associated with a gradual decline in hepatic IGF-I production which makes teleological sense due to the insulin-like effects of IGF-I. A study by Ho et al. suggests that GH-induced hepatic IGF-I production is regulated by portal insulin levels. They reported that insulin promotes the translocation of the hepatic GH receptor (GHR) to the surface. When portal insulin levels are high, the liver becomes GH sensitive, regardless of the cause of the

elevation in insulin production. In addition, portal insulin also inhibits hepatic IGFBP-1 production, which may increase the bioavailability of circulating IGF-I. In conclusion, high portal insulin levels increase liver GH sensitivity (via up regulation of surface GHRs) and therefore, ultimately increase liver IGF-I production with concomitant increases in serum

IGF- I levels. In contrast, low portal insulin levels reduce the sensitivity of liver for GH and,

therefore, reduce serum IGF-I levels.