Insulin-like growth factors and pancreas beta cells

• Published in: European journal of clinical investigation 2004-04, Vol.34 (4), p.249-255
• Main Authors: Van Haeften, T. W., Twickler, Th. B.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; General aspects; Humans; IGF-1; IGF-2; Insulin - metabolism; Insulin Resistance - physiology; insulin secretion; Insulin-Like Growth Factor I - physiology; Insulin-Like Growth Factor II - physiology; Islets of Langerhans - growth & development; Islets of Langerhans - physiopathology; Medical sciences; Rats; Signal Transduction - physiology; Somatomedins - physiology; type 2 diabetes
• ISSN: 0014-2972; 1365-2362
• DOI: 10.1111/j.1365-2362.2004.01337.x

Insulin‐like growth factors (IGFs) have been implicated in normal growth, and especially foetal pancreas beta‐cell development. As low birth weight has been implicated in the development of obesity and type 2 diabetes, much research has evolved into the importance of IGF and their signalling pathways for pancreas beta‐cell development, and for type 2 diabetes. Insulin‐like growth factor‐I signalling has a lot in common with insulin signalling, and is involved in diverse cellular effects such as antiapoptosis, protein synthesis, cell growth and mitogenesis. Insulin‐like growth factor‐II can be bound by the insulin receptor A subtype and the IGF‐1 receptor, which may explain its antiapoptotic effect. Various knock‐out model studies indicate that absence of IGF‐I or the IGF‐1 receptor is critical for foetal and postnatal growth. Similarly, knock‐out models of post‐receptor molecules (such as IRS‐2) point to the physiological role of IGFs for pancreas beta‐cell development. A beta‐cell‐specific IGF‐1 receptor knock out model indicates the importance of IGF‐I for beta‐cell function. The Goto‐Kakizaki (GK) rat, a model for diabetes, has insufficient beta‐cell development, which may be related to its defective IGF‐II synthesis. As normal pancreas beta cells adapt to the prevailing insulin resistance with increasing beta‐cell function, it is possible that insulin resistance interacts with IGF signalling in pancreas beta cells.