Arginine-Induced Insulin Release in Glucokinase-Deficient Subjects
| Autor: | Maria E. Pueyo, Karine Clément, Jean-Jacques Robert, Philippe Passa, Philippe Froguel, Martine Vaxillaire, Gilberto Velho |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Arginine Endocrinology Diabetes and Metabolism medicine.medical_treatment Population Radioimmunoassay Islets of Langerhans In vivo Internal medicine Diabetes mellitus Glucokinase Internal Medicine medicine Humans Insulin Glycolysis Infusions Intravenous education Pancreatic hormone Advanced and Specialized Nursing education.field_of_study C-Peptide Dose-Response Relationship Drug business.industry Glucose Tolerance Test Middle Aged medicine.disease Glucose Endocrinology Hyperglycemia Glucose Clamp Technique Regression Analysis Female business |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/diacare.17.9.1015 |
| Popis: | OBJECTIVE In eight glucokinase (GCK)-deficient subjects, we have investigated insulin secretion rates (ISRs) in response to intravenous arginine. Impairment in the enzymatic activity of mutant GCK leads to a reduced glycolytic flux in β-cells. This defect translates in vivo as a right shift in the glucose/ISR dose-response curve. Insulin secretion in response to other secretagogues has not been reported. RESEARCH DESIGN AND METHODS The arginine test was performed immediately after a 2-h hyperglycémie (10 mM) clamp. ISR was computed by decon-volution of peripheral C-peptide levels. Linear regression analyses were performed to assess correlations between the /3-cell secretory responses to the arginine test, an intravenous glucose tolerance test (IVGTT), and a hyperglycemie clamp (areas under the C-peptide curves), and between these parameters and the glucose tolerance status (area under the glucose curve during an oral glucose tolerance test). RESULTS Two minutes after the injection of arginine, the increment in ISR was 30.17 ± 10.01 pmol insulin · kg−1 · min−1 in patients and 36.25 ± 15.46 pmol insulin · kg−1 · min−1 in control subjects (P = 0.38). Throughout the experiment, increments in ISR were comparable in both groups. The amount of insulin secreted in response to arginine (0-5 min) was similar in patients and control subjects: 81 ± 28 vs. 119 ± 55 pmol/kg (P = 0.16), respectively. The arginine test C-peptide response was not correlated with the IVGTT or hyperglycémie clamp responses. The arginine test and hyperglycemie clamp responses were not correlated to the glucose tolerance status. The best predictor of the glucose tolerance was the C-peptide response to the IVGTT (r2 = 0.78; P = 0.002). CONCLUSIONS β-cell secretory increment in response to arginine was found to be in the normal range in GCK-deficient subjects. The arginine test does not seem to reflect either the /3-cell secretory defect or the glucose tolerance status of these subjects. IVGTT seems to be the best predictor of the latter parameter in this population. |
| Databáze: | OpenAIRE |
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