Summary
Recent evidence suggests possible linkage between diabetes mellitus and mitochondrial gene mutation. We surveyed mitochondrial tRNALEU(UUR) (3243) mutation in 7 mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) families and identified 24 mutated subjects (7 MELAS probands and 17 non-MELAS relatives) as well as 11 non-mutant family members. An OGTT in the 24 mutant relatives revealed 14 diabetic subjects, 3 with impaired glucose tolerance and 7 with normal glucose tolerance and all non-mutant family members as having normal glucose tolerance. Insulinogenic index was significantly reduced in the mutant diabetic subjects and those with impaired and normal glucose tolerance in comparison with the normal control subjects and the non-mutant members. Urinary 24-h C-peptide immunoreactivity excretion was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance, compared with the control subjects and the non-mutant family members. Plasma C-peptide immunoreactivity 6 min after glucagon injection was markedly reduced in the mutant diabetic subjects and those with normal and impaired glucose tolerance compared with the control subjects and the non-mutant family members. Si, an index of insulin sensitivity of the four mutant subjects was within normal range. Islet cell antibodies were negative in sera of eight mutated diabetic subjects, 2 and 6 with impaired and normal glucose tolerance, respectively. Diabetic retinopathy and nephropathy were demonstrated in 7 (50%) and 12 (85.7%) of 14 mutant diabetic subjects, respectively. Neurosensory deafness was demonstrated in 12 (85.7%) of 14 mutated diabetic subjects, (66.7%) of 3 mutated impaired glucose tolerant subjects, but not detected in 6 mutated normal glucose tolerant subjects and 11 non-mutant family members. These findings suggest that the tRNALEU(UUR) mutation is associated with pancreatic beta-cell secretory defect of insulin.
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Abbreviations
- MELAS:
-
Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
- OGTT:
-
oral glucose tolerance test
- IGT:
-
impaired glucose tolerance
- NGT:
-
normal glucose tolerance
- IRI:
-
insulin-like immunoreactivity
- CPR:
-
C-peptide immunoreactivity
- ICA:
-
islet cell antibodies
- mtDNA:
-
mitochondrial DNA
- CPEO:
-
chronic external ophthalmoplegia
- NIDDM:
-
non-insulin-dependent diabetes mellitus
- AER:
-
albumin excretion rate
- KSS:
-
Kearns-Sayre syndrome
- IDDM:
-
insulin dependent diabetes mellitus
- GAD-Ab:
-
glutamic acid decarboxylase antibody
- Kb:
-
kilobase
- bp:
-
base pair
- BS:
-
blood sugar
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Suzuki, S., Hinokio, Y., Hirai, S. et al. Pancreatic beta-cell secretory defect associated with mitochondrial point mutation of the tRNALEU(UUR) gene: a study in seven families with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS). Diabetologia 37, 818–825 (1994). https://doi.org/10.1007/BF00404339
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DOI: https://doi.org/10.1007/BF00404339