The role of the growth hormone–insulin‐like growth factor axis in glucose homeostasis

Abstract

Homeostatic mechanisms normally maintain the plasma glucose concentration within narrow limits despite major fluctuations in supply and demand. There is increasing evidence that the growth hormone (GH)-insulin-like growth factor (IGF) axis may play an important role in glucose metabolism. GH has potent effects on intermediary metabolism, some of which antagonize the actions of insulin. In contrast, IGF-I has insulin-like actions, which are, in the case of glucose metabolism, opposite to those of GH. There is often deranged glucose metabolism in situations where GH is deficient or in excess. The clinical administration of GH or IGF-I results in altered glucose metabolism and changes in insulin resistance. Despite these observations, the precise role of GH and IGF-I and their interactions with insulin in controlling normal glucose homeostasis are unknown. In diabetes, GH secretion is abnormally increased as a result of reduced portal insulin resulting in impaired hepatic IGF-I generation. Evidence suggests that this may contribute to the development of diabetic microvascular complications. IGF-I 'replacement' in diabetes is under investigation and new methods of delivering IGF-I as a complex with IGFBP-3 offer exciting new prospects.

Beneficial effect of recombinant human growth hormone on the intestinal mucosa barrier of septic rats

“…GH binding to GHRs through the ability of the intestinal mucosa to take up and utilize glutamine could promote growth differentiation and wound repair of the intestinal mucosa, ameliorate the impairment of the intestinal mucosa and maintain the structure and function of the intestinal mucosa barrier (9). The GH/IGF-1 axis is present in the body (10)(11)(12)(13)(14). GH binding to GHRs could increase IGF-1 lev- GH is an important anabolic hormone.…”

Diabetes in chronic liver disease: from old concepts to new evidence

“…In transgenic mice that overexpress GH, hypertriglyceridaemia, hyperinsulinaemia, hyperglycaemia and insulin resistance can be observed [77]. Molecular abnormalities found in this animal model include a reduced number of IR in the liver, with preserved insulin affinity, increased PI3K activity and increased PI3K-IRS-1 association [77]. Moreover, reduced glucokinase activity and reduced concentration of GLUT-2 mRNA have also been reported in this model [78].…”

“…GH is a wellknown counter-regulatory hormone involved in insulin resistance. In a recent review, Holt et al pointed out that GH can affect glucose metabolism in different ways, directly by interfering with insulin action, and indirectly through its effects on lipid metabolism [77]. The latter involves the role of GH in the increase of FFA levels.…”

“…Increased FFA levels provoke, in turn, increased hepatic glucose output and reduced peripheral glucose oxidation [33]. In transgenic mice that overexpress GH, hypertriglyceridaemia, hyperinsulinaemia, hyperglycaemia and insulin resistance can be observed [77]. Molecular abnormalities found in this animal model include a reduced number of IR in the liver, with preserved insulin affinity, increased PI3K activity and increased PI3K-IRS-1 association [77].…”

Avaliação da estatura final atingida por pacientes com diabetes melito tipo 1 acompanhados em serviço terciário

“…O déficit de crescimento estatural, observado no DM1, é multifatorial, mas também pode estar relacionado ao eixo hipotálamo-hipófise-IGF-1, pela existência de uma alça de retroalimentação negativa da IGFBP-1 com a insulina (3,4). Nos portadores de DM1, em fase de crescimento e desenvolvimento, concentrações reduzidas de insulina levam a um aumento dos níveis de IGFBP-1, que, se ligando mais a IGF-1, inibem sua atividade, prejudicando o controle metabólico (5) e o crescimento celular, a despeito das concentrações elevadas de GH.…”