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


METHODS
The function of alpha- and beta-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.
Brändle
M
M
Division of Endocrinology and Diabetes, Department of Internal Medicine, University Hospital, Zürich, Switzerland. michael.braendle@dim.usz.ch
Lehmann
R
R
Maly
F E
FE
Schmid
C
C
Spinas
G A
GA
D000328:Adult; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics*; D003638:Deafness / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D018392:Genomic Imprinting; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009679:Nuclear Family; D010375:Pedigree; D017354:Point Mutation; D012313:RNA / Q000235:genetics*; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu / Q000235:genetics*; D012016:Reference Values; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D004272:DNA, Mitochondrial; D007328:Insulin; D000077278:RNA, Mitochondrial; D012356:RNA, Transfer, Leu; D012313:RNA; D005934:Glucagon; D001120:Arginine