Major Circadian Variations of Glucose Homeostasis in a Patient with Rabson-Mendenhall Syndrome and Primary Insulin Resistance Due to a Mutation(Cys284 → Tyr) in the Insulin Receptor α-Subunit
| Autor: | Jocelyne Magré, C Daubas, Jacqueline Capeau, Martine Caron, Jean-Jacques Robert, S Rizkalla, Christèle Desbois-Mouthon, J Duprey, B Chevallier, M. J. Blivet-Van Eggelpoël, M Gourmelen |
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| Rok vydání: | 1997 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Developmental Disabilities medicine.medical_treatment DNA Mutational Analysis In Vitro Techniques Glucagon Insulin resistance Internal medicine medicine Homeostasis Humans Insulin Point Mutation Glucose homeostasis Amino Acid Sequence Insulin-Like Growth Factor I Child Base Sequence biology Human Growth Hormone Syndrome medicine.disease Receptor Insulin Circadian Rhythm Insulin oscillation Insulin-Like Growth Factor Binding Proteins Insulin receptor Glucose Endocrinology Pediatrics Perinatology and Child Health biology.protein Ketonuria Insulin Resistance Rabson–Mendenhall syndrome |
| Zdroj: | Pediatric Research. 42:72-77 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/00006450-199707000-00012 |
| Popis: | We have performed clinical, in vitro biochemical, and genetic studies of a patient with severe insulin resistance, considerable growth restriction, and Rabson-Mendenhall syndrome (patient RM-3). The blood IGF-I level was undetectable in this patient, although the GH level was moderately decreased. During the postprandial period, glycemia, ketonuria, and plasma glucagon were very elevated despite high doses of exogenous insulin (glucose levels up to 30 mmol/L). In the postabsorptive state, blood glucose was normalized with small amounts of insulin; ketonuria, and glucagon levels were reduced but remained supranormal. Erythrocytes and cultured skin fibroblasts from the patient displayed a decrease in cell surface insulin receptors (IRs). The ability of physiologic concentrations of insulin to stimulate metabolic processes was altered in patient fibroblasts. Analysis of the IR gene by denaturing gradient gel electrophoresis and direct sequencing showed a homozygous missense mutation in exon 3, replacing Cys284 by Tyr in the alpha-subunit. In conclusion, marked primary insulin resistance was evidenced in patient cells as a result of a structural alteration in the IR alpha-subunit. The in vitro studies could not account alone for the in vivo metabolic alterations because glucose homeostasis varied considerably during the day in the patient. |
| Databáze: | OpenAIRE |
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