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.

Abstract

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.

RESEARCH DESIGN AND 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.

• Authors: M Brändle, R Lehmann, F E Maly, C Schmid, G A Spinas
• Journal: Diabetes care (Diabetes Care) Vol. 24 Issue 7 Pg. 1253-8 (Jul 2001) ISSN: 0149-5992 [Print] United States
• PMID: 11423511 (Publication Type: Case Reports, Comparative Study, Journal Article)

Chemical References

• Blood Glucose
• C-Peptide
• DNA, Mitochondrial
• Insulin
• RNA, Mitochondrial
• RNA, Transfer, Leu
• RNA
• Glucagon
• Arginine

Topics

• Adult
• Arginine
• Blood Glucose (metabolism)
• C-Peptide (blood, metabolism)
• DNA, Mitochondrial (genetics)
• Deafness (complications, genetics, physiopathology)
• Diabetes Complications
• Diabetes Mellitus (genetics, physiopathology)
• Female
• Genomic Imprinting
• Glucagon (blood, metabolism)
• Glucose Tolerance Test
• Humans
• Insulin (blood, metabolism)
• Insulin Secretion
• Islets of Langerhans (drug effects, metabolism)
• Kinetics
• Male
• Nuclear Family
• Pedigree
• Point Mutation
• RNA (genetics)
• RNA, Mitochondrial
• RNA, Transfer, Leu (genetics)
• Reference Values
• Time Factors