The Fascinating Interplay between Growth Hormone, Insulin-Like Growth Factor-1, and Insulin

Abstract

This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

Keywords: Acromegaly; Diabetes mellitus, type 1; Diabetes mellitus, type 2; Growth hormone; Humans; Insulin; Insulin-like growth factor I.

Fig. 1.

The positive effect of insulin on the liver sensitivity for growth hormone (LSG). In this way, portal vein insulin levels can control insulin-like growth factor-1 (IGF-1) generation by growth hormone (GH).

Fig. 2.

In type 1 diabetes mellitus, portal vein insulin levels are extremely low. This significantly decreases liver sensitivity for growth hormone (LSG). Therefore, insulin-like growth factor-1 (IGF-1) levels drop, and due to the lack of negative feedback by IGF-1 on the hypothalamus, growth hormone (GH) levels increase significantly.

Fig. 3.

In type 2 diabetes mellitus, portal vein insulin levels are elevated to compensate for the insulin-resistant state of the body. This significantly increases liver sensitivity for growth hormone (LSG). Therefore, insulin-like growth factor-1 (IGF-1) levels are high in the normal range. Due to the negative feedback by IGF-1 on the hypothalamus, growth hormone (GH) levels decrease significantly. The low GH/insulin ratio will stimulate lipogenesis and inhibit lipolysis. The net result is the tendency to increase body weight.

Fig. 4.

In liver insufficiency, the liver fails to produce enough insulin-like growth factor-1 (IGF-1). The storage of glycogen is also hampered. Therefore, portal vein insulin levels are low. This decreases liver sensitivity for growth hormone (LSG). Therefore, IGF-1 levels further drop and, due to the lack of negative feedback by IGF-1 on the hypothalamus, growth hormone (GH) levels increase significantly. These GH levels result in an often severe state of catabolism, with significant proteolysis and lipolysis.

Fig. 5.

In acromegaly, the somatotropinoma in the anterior pituitary produces excessive amounts of growth hormone (GH). This induces severe insulin resistance. Therefore, portal vein insulin levels are high. High portal insulin concentrations significantly increase liver sensitivity for growth hormone (LSG). This only makes the situation worse, as the high GH levels only further increase the already elevated insulin-like growth factor-1 (IGF-1) concentrations. Thus, in acromegaly, IGF-1 levels are elevated because of the somatotropinoma, but also because of the elevated insulin levels in the portal vein.