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Diminished Insulin Secretory Response to Glucose but Normal Insulin and Glucagon Secretory Responses to Arginine in a Family With Maternally Inherited Diabetes and Deafness Caused by Mitochondrial tRNA^LEU(UUR) Gene Mutation

¹ Division of Endocrinology and Diabetes, Department of Internal Medicine, and the
² Institute of Clinical Chemistry, University Hospital, Zürich, Switzerland

OBJECTIVE—The effects of glucose, arginine, and glucagon on ß-cell function as well as -cell response to arginine were studied in a family with mitochondrial diabetes.

RESEARCH DESIGN AND METHODS—The function of - and ß-cells was assessed in all five siblings carrying the mitochondrial tRNA Leu(UUR) gene mutation at position 3243 and compared with six sex-, age-, and weight-matched control subjects. Insulin and C-peptide responses were evaluated by intravenous glucagon application, intravenous arginine stimulation test, and intravenous glucose tolerance test. Glucagon secretion was assessed during the arginine stimulation test.

RESULTS—The glucose disappearance constant (K_g) value (mean ± SEM 0.61 ± 0.04 vs. 1.1 ± 0.04, P = 0.0002) as well as the acute insulin response to glucose (area under the curve [AUC] 0–10 min, 77.7 ± 50.7 vs. 1,352.3 ± 191.5 pmol/l, P = 0.0004) were decreased in all patients. Similarly, glucagon-stimulated C-peptide response was also impaired (728 ± 111.4 vs. 1,526.7 ± 157.7 pmol/l, P = 0.005), whereas the insulin response to arginine (AUC) was normal (1,346.9 ± 710.8 vs. 1,083.2 ± 132.5 pmol/l, P = 0.699). Acute glucagon response to arginine (AUC) was normal but tended to be higher in the patients than in the control subjects (181.7 ± 47.5 vs. 90.0 ± 21.1 pmol/l, P = 0.099).

CONCLUSIONS—This study shows impaired insulin and C-peptide secretion in response to a glucose challenge and to glucagon stimulation in diabetic patients with mitochondrial tRNA Leu(UUR) gene mutation, although insulin and glucagon secretory responses to arginine were normal.

Abbreviations: AIR_g, acute insulin response to glucose • AUC, area under the curve • CV, coefficient of variation • IGT, impaired glucose tolerance • IVGTT, intravenous glucose tolerance test • K_g, glucose disappearance constant • MIDD, maternally inherited diabetes and deafness

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