Alterations in the growth hormone-insulin-like growth factor axis in insulin dependent diabetes mellitus


Bereket A. , Lang C., Wilson T.

HORMONE AND METABOLIC RESEARCH, cilt.31, ss.172-181, 1999 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 31
  • Basım Tarihi: 1999
  • Doi Numarası: 10.1055/s-2007-978716
  • Dergi Adı: HORMONE AND METABOLIC RESEARCH
  • Sayfa Sayıları: ss.172-181

Özet

The growth hormone (GH)-insulin-like growth factor (IGF) axis and insulin are major anabolic effecters in promoting weight gain and linear growth. These two anabolic systems are interlinked at many levels, thus abnormalities in one of these systems effect the other causing disordered metabolic homeostasis. Insufficient portal insulinization in insulin dependent diabetes mellitus (IDDM) results in hepatic CH resistance and increased production of ICF-binding proteins-1 (IGFBP-1) and IGFBP-2. CH resistance is reflected by decreased hepatic IGF-l production. In addition, changes in other CH-dependent proteins are also observed in IDDM. Increased proteolysis of IGFBP-3 results in reduction of intact IGFBP-3. Serum ALS levels are also slightly diminished in untreated diabetic patients. Hepatic resistance to GH is, at least in part, caused by diminished GH receptors as reflected by diminished circulating GHBP levels. In addition, there is also evidence from experimental and human studies suggesting post-receptor defect(s) in GH action. As a result of these changes, circulating total and free IGF-l levels are decreased during insulinopenia. Lack of negative feed-back effect of IGF-l on GH secretion causes CH hypersecretion which increases hyperglycemia by decreasing sensitivity to insulin. CH hypersecretion in poorly controlled diabetic patients may play a role in the pathogenesis of diabetic vascular complications. Most of these abnormalities in the GH-ICF axis in diabetes are reversed by effective insulinization of the patient. Addition of IGF-I treatment to insulin in adolescents with IDDM allows correction of GH hypersecretion, improves insulin sensitivity and glycemic control, and decreases insulin requirements. The effect of IGF-l treatment on diabetic complications has yet to be seen.