Long-term effect of recombinant human insulin-like growth factor I on metabolic and growth control in a patient with leprechaunism
| Autor: | Mikiko Kato, Kenji Fujieda, Nozomi Shinohara, Mari Murashita, Jun Nakae, Toshihiro Tajima |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Blood Glucose
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Drug Resistance Growth Biochemistry Receptor IGF Type 1 Endocrinology Insulin resistance Japan Internal medicine medicine Humans Insulin-Like Growth Factor I Phosphorylation Receptor Fibroblast Child Cells Cultured Growth Disorders Glucose tolerance test medicine.diagnostic_test business.industry Human Growth Hormone Insulin Growth factor Biochemistry (medical) DNA Fibroblasts medicine.disease Recombinant Proteins medicine.anatomical_structure Insulin-Like Growth Factor Binding Protein 3 Metabolic control analysis Female Donohue syndrome business |
| Zdroj: | The Journal of clinical endocrinology and metabolism. 83(2) |
| ISSN: | 0021-972X |
| Popis: | Leprechaunism is the most severe form of insulin resistance, manifesting with abnormal glucose metabolism and retarded growth. In the present study, we investigated the biological actions of recombinant human insulin-like growth factor I (rhIGF-I) in fibroblasts derived from a patient with leprechaunism. In the same patient, we also investigated the pharmacokinetics of IGF-I and the long-term effect of rhIGF-I treatment on metabolic control and physical growth. The patient’s fibroblasts showed normal binding of IGF-I, normal phosphorylation of the β-subunit of the IGF-I receptor, and normal[ 3H]thymidine incorporation in response to IGF-I. The fibroblast studies suggested that the patient would respond to IGF-I therapy, but certainly did not exclude the possibility of IGF-I resistance in vivo. Administration of recombinant human GH at the dose of 2.0 IU/kg for 3 consecutive days induced a minimal response of serum total IGF-I and IGF-binding protein-3 (IGFBP-3), suggesting partial GH resistance. To increase the serum total IGF-I level, we administered rhIGF-I with combination therapy of intermittent and continuous sc injection. This sustained the serum total IGF-I level, but not the serum IGFBP-3 level, within the normal range. The patient was treated with combination therapy of rhIGF-I by both sc injection and continuous sc infusion for 6 yr and 10 months. Administration of rhIGF-I at total daily dose of 1.6 mg/kg maintained her growth rate and hemoglobin A1c level nearly within the normal range. These findings suggest 1) that this leprechaun patient has an IGF-Ideficient state and partial GH resistance, as reflected by impaired production of IGF-I and IGFBP-3; 2) that rhIGF-I treatment works effectively for preventing postnatal growth retardation and normalizing glucose metabolism in patients with extreme insulin resistance; 3) that this treatment requires relatively higher dose of rhIGF-I; and 4) that treatment appears to be safe and devoid of adverse effects. |
| Databáze: | OpenAIRE |
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