Postreceptor Crosstalk on PI3K/Akt between GH and Insulin in Non-Catch-Up Growth Rats Born Small for Gestational Age

• Published in: Hormone research Vol. 70; no. 1; pp. 29 - 35
• Main Authors: Huang, Ting-Ting, Du, Minlian, Kuluz, John W., Li, Yanhong, Ma, Huamei
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2008
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Animals; Animals, Newborn; Birth Weight - drug effects; Diabetes Mellitus, Type 2 - chemically induced; Diabetes Mellitus, Type 2 - enzymology; Diabetes Mellitus, Type 2 - etiology; Disease Models, Animal; Enzyme Inhibitors - pharmacology; Female; Gestational Age; Growth Disorders - chemically induced; Growth Disorders - enzymology; Growth Hormone - secretion; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin - metabolism; Insulin - pharmacology; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Original Paper; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; Pregnancy; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Tyrphostins - pharmacology; Insulin receptor substrate-1; Insulin resistance; Growth hormone resistance; Small for gestational age; Phosphatidylinositol 3′-kinase
• ISSN: 1663-2818; 1663-2826; 1423-0046
• DOI: 10.1159/000129675

Background/Aims: Children born small for gestational age (SGA) are at increased risk for short stature and type 2 diabetes mellitus as a result of growth hormone (GH) resistance and insulin resistance. The mechanisms of multiple hormone resistance remain unclear. This study was designed to investigate the relationship between GH resistance and insulin resistance in non-catch-up growth (NCU-SGA) rats, and how their signaling pathways are related based on their crosstalk on the insulin receptor substrate-1 phosphatidylinositol 3′-kinase (IRS-1-PI3K) pathway. Methods: NCU-SGA rat model was developed by restricting prenatal food intake in pregnant dams. Activated levels of IRS-1 and Akt in liver protein extracts were compared between NCU-SGA and age- and sex-matched controls born appropriate for gestational age rats at baseline, after insulin stimulation, and after pretreatment with AG490 (GH-JAK2 pathway inhibitor) followed by insulin stimulation. Results: GH secretion was positively related to markedly increased insulin levels in NCU-SGA rats. There was no difference of IRS-1 phosphorylation in response to insulin between two groups, however, insulin-stimulated Akt phosphorylation was attenuated in NCU-SGA rats compared to appropriate for gestational age rats. Pretreatment with AG490 restored the Akt response to insulin demonstrated by significantly increased Akt phosphorylation. Conclusion: GH plays a role in inducing insulin resistance via signaling crosstalk with insulin at the level of PI3K/Akt in NCU-SGA rats.