Insulin-like growth factor-1 deficiency and metabolic syndrome

Abstract

Consistent evidence associates IGF-1 deficiency and metabolic syndrome. In this review, we will focus on the metabolic effects of IGF-1, the concept of metabolic syndrome and its clinical manifestations (impaired lipid profile, insulin resistance, increased glucose levels, obesity, and cardiovascular disease), discussing whether IGF-1 replacement therapy could be a beneficial strategy for these patients. The search plan was made in Medline for Pubmed with the following mesh terms: IGF-1 and "metabolism, carbohydrate, lipids, proteins, amino acids, metabolic syndrome, cardiovascular disease, diabetes" between the years 1963-2015. The search includes animal and human protocols. In this review we discuss the relevant actions of IGF-1 on metabolism and the implication of IGF-1 deficiency in the establishment of metabolic syndrome. Multiple studies (in vitro and in vivo) demonstrate the association between IGF-1 deficit and deregulated lipid metabolism, cardiovascular disease, diabetes, and an altered metabolic profile of diabetic patients. Based on the available data we propose IGF-1 as a key hormone in the pathophysiology of metabolic syndrome; due to its implications in the metabolism of carbohydrates and lipids. Previous data demonstrates how IGF-1 can be an effective option in the treatment of this worldwide increasing condition. It has to distinguished that the replacement therapy should be only undertaken to restore the physiological levels, never to exceed physiological ranges.

Fig. 1

Metabolic effects of IGF-1, GH, and insulin under physiological conditions on their target organs. The figure summarises schematically some of the metabolic effects that IGF-1 (blue continuous line), GH (red discontinuous line), and insulin (green dotted line) exert on kidney (upper left), brain (upper centre), skeletal muscle (left), liver (centre), adipose tissue (right), and pancreas (bottom). GH growth hormone, GHRH growth hormone releasing hormone, FFA free fatty acid, IRS insulin receptor substrate, IGF-1 insulin-like growth factor 1, IGBBP-1 insulin-like growth factor binding protein 1

Fig. 2

Metabolic effects of IGF-1 and GH under pathological conditions. The figure summarises schematically some of the metabolic mechanisms altered in obesity and the role that IGF-1 and GH exert on them