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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutation in the mitochondrial gene at position 3243 was recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondria play an important role in glucose-stimulated insulin secretion in pancreatic beta-cells, we therefore searched for such mutations to detect a candidate gene for diabetes. We screened 10 diabetic subjects with clinical features suggesting mitochondrial DNA mutations. An adenine to guanine point mutation in tRNA(Lys) in at position 8296 (the 8296 mutation) was newly identified. Subsequently, we screened 1216 diabetic subjects, 44 patients with sensorineural deafness subjects and 300 non-diabetic control subjects for this mutation. We identified the mutation in 11 (0.90%) unrelated diabetic subjects, one (2.3%) patient with deafness and no non-diabetic control subject. Seven of these 12 subjects showed maternal inheritance. Deafness was seen in 7 of 12 probands. Four family pedigrees showed maternal inheritance of diabetes over two or three generations. Subjects carrying the 8296 mutation may develop diabetes and the mutation can explain as high as ca. 1% of the causes of diabetes.
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PMID:Novel mitochondrial DNA mutation in tRNA(Lys) (8296A-->G) associated with diabetes. 957 Nov 88

In this report, cardiac abnormalities in 2 diabetic patients with a mutation in the mitochondrial tRNA(Leu)(UUR)gene are described. The 2 patients exhibited left ventricular dilation and diffuse decreased wall motion. Cardiac catheterization studies revealed normal coronary angiography. In both patients, light microscopic examination of hematoxylin and eosin-stained sections revealed myocyte hypertrophy and perinuclear vacuolization and electron microscopy revealed an increase in the number and size of mitochondria and abnormal configuration of cristae. These findings suggest that mutations in mitochondrial DNA, such as an A-->G mutation at position 3243, should be considered as a cause not only of diabetes mellitus but also of cardiac involvement in patients with diabetes mellitus.
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PMID:Diabetes mellitus and cardiomyopathy--association with mutation in the mitochondrial tRNA(Leu)(UUR) gene. 958 68

A 34-year-old female IDDM patient complained of chest oppression in hypoglycemic episodes and electrocardiograms revealed reversible ischemic changes occurring concomitantly with hypoglycemia. The ECG changes improved and the chest oppression disappeared following increasing blood glucose level by glucose intake. Master's double load test and treadmill load test were positive for ischemic changes. Radioisotopic myocardial scintigraphy by thallium and BMIPP did not show any filling defects and coronary angiography revealed no remarked stenosis in the coronary arteries. She had no mitochondrial tRNA(Leu) (A-->G) gene mutation at nucleotide position 3243, but both the patient and her mother had a G-to-A transition within the replication origin of the light strand at nucleotide position 5744 of the mitochondrial gene. As the patient's maternal family had no history of ischemic heart disease, it is not clear whether mitochondrial gene mutation at nucleotide position 5744 reflects the occurrence of cardiac ischemia. Some disorders of microcirculation in capillary vessels in cardiac muscles may occur in such patients.
Diabetes Res Clin Pract 1998 Jan
PMID:An IDDM patient who complained of chest oppression with ischemic changes on ECG in insulin-induced hypoglycemia. 959 72

Mitochondrial tRNA(Leu)(UUR) gene mutation is one of the candidates in the pathogenesis of NIDDM. Especially the 3243 (A-->G) mutation is associated with the maternally-inherited diabetes and deafness. To evaluate the prevalence and characteristics of the 3243 point mutation in Koreans, we screened 433 Korean diabetic patients (220 men and 213 women). Genomic DNA was extracted from peripheral white blood cells and PCR was carried out with mitochondrial DNA primers (3130-3149, 3558-3539) encompassing the 3243 position. After digestion with Apa-1, five subjects showed polymorphism suggesting 3243 point mutation but when we directly sequenced the amplified DNA with an automatic sequencer, only 2 of the 5 patients were shown to have 3243 (A-->G) mutation and the other 3 subjects had 3426 (A-->G) mutation rather than 3243 mutation. Two diabetic patients with 3243 mutation were lean (BMI = 14.4, 17.0 kg/m2), had relatively lower fasting C-peptide concentrations (0.9 ng/ml each), and required insulin for management. In contrast, those with 3426 point mutation were not lean (BMI = 22.6-28.0 kg/m2), had relatively higher C-peptide levels (3.9-5.4 ng/ml), and could be managed with oral hypoglycemic agents. None of the 5 patients had deafness. In conclusion, the prevalence of 3243 point mutation in Korean diabetic patients was approximately 0.5% and we found a new mutation mimicking 3243 mutation by PCR-RFLP (restriction fragment length polymorphism) pattern. We suggest that sequencing of the PCR product or designing smaller PCR fragment size to enhance the specificity may help to identify the exact location of the point mutation.
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PMID:A new point mutation (3426, A to G) in mitochondrial NADH dehydrogenase gene in Korean diabetic patients which mimics 3243 mutation by restriction fragment length polymorphism pattern. 962 53

We report a study of 10 candidate genes presumably involved in diabetes or insulin resistance or obesity among Pondicherian Tamil Indians, an isolated population with a high prevalence of diabetes. Forty-nine families with at least two affected patients in the sibship (567 individuals) were selected and tested by PCR-RFLP techniques for reported mutations in 10 diabetes or obesity candidate genes: glucagon receptor, insulin receptor substrate 1, insulin receptor, human beta 3 adrenergic receptor, fatty acid binding protein 2, mitochondrial tRNA(Leu(UUR)), sulphonylurea receptor, human uncoupling protein and the glycogen-associated regulatory subunit of protein phosphatase-1. Glucokinase gene was also screened for mutations. No mutations were found in glucokinase, glucagon receptor and mitochondrial genes in any of the 49 probands. Frequencies of polymorphisms at other loci were similar to those reported in Caucasian populations, except for 4 of the loci at which a higher frequency of variants was observed: human beta 3 adrenergic receptor, human uncoupling type 1 protein, fatty acid binding protein 2 and the glycogen-associated regulatory subunit of protein phosphatase-1. However, no evidence of association between any of these gene variants and non-insulin-dependent diabetes mellitus (NIDDM) or quantitative traits related to NIDDM (including body mass index, waist/hip ratio, insulinaemia, glycaemia, triglycerides and total cholesterol) was found in our sample. These results suggest that none of these gene variants commonly found in the Pondicherian Tamil population of South India is a major NIDDM predisposing locus, although it cannot be excluded that they may contribute to the polygenic background of the metabolic syndrome in Pondichery.
Diabetes Metab 1998 Jun
PMID:Genetic studies of polymorphisms in ten non-insulin-dependent diabetes mellitus candidate genes in Tamil Indians from Pondichery. 969 58

Patients who have mitochondrial myopathy can present with specific pathological conditions (eg, diabetes mellitus and deafness). A 36-year-old woman presented with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). An investigation was conducted into whether the abnormalitiy of mitochondrial DNA (a T to C transition at position 3271 in the mitochondrial tRNA [Leu(UUR)] gene) influences nuclear DNA synthesis by cells in the heart, skeletal muscles, and brain. Myocardium, skeletal muscle, and brain tissues were stained with hematoxylin-eosin, and Masson trichrome for histopathology. Target nuclei taken from the myocardial and skeletal muscles and brain tissue were purified after removing debris by the modified Hedley method. These nuclei were stained with propidium iodide (PI) for analysis by flow cytometry. The number of nuclei in the G2M phase was bigger in myocytes of MELAS than in normal myocytes (Control) (MELAS myocyte: Control myocyte=24.9+/-7.3: 6.1+/-1.6%, p<0.005), but there was no significant increase in the G2M phase in brain tissue. The G1 phase was far more reduced in MELAS myocytes and skeletal muscle than in Controls (MELAS myocyte: Control myocyte=65.8+/-9.1: 88.0+/-3.2%, p<0.005; MELAS skeletal muscle: Control skeletal muscle=85.1+/-2.2: 90.1+/-3.2%, p<0.05), while there was no significant decrease of nuclei in the G1 phase in brain tissue. Increased amount of nuclei in the G2M phase in cardiac myocytes and skeletal muscle cells compared with that in neurons might depend on the capacity for proliferation and differentiation of these cells as compared with brain tissue. It was concluded that the mitochondrial DNA mutation (3271T-to-C) of MELAS may influence the nuclear DNA synthesis of cells in various tissues depending on their level of mitotic activity.
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PMID:Cell cycle of myocytes of cardiac and skeletal muscle in mitochondrial myopathy. 976 10

The mitochondrial A3243G mutation of the tRNA(Leu) has been described in pedigrees with maternally inherited diabetes mellitus and deafness. Ten diabetic patients with sensorineural deafness were studied. Polymerase chain reaction and enzyme restriction analysis with Apa I were performed. The mutation was found in heteroplasmy in only one patient (1/10). She was a 43-years-old woman with maternally inherited diabetes and deafness since she was 29. The association of sensorineural deafness and maternal inherited diabetes are the clues to suspect this subtype of diabetes.
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PMID:[Diabetes mellitus associated with the A3243G mutation of mitochondrial DNA. Apropos a case]. 1007 17

Cardiac involvement and its clinical course in a diabetic patient with a mitochondrial tRNA(Leu)(UUR) mutation at position 3243 is reported in a 54-year-old man with no history of hypertension. At age 46, an electrocardiogram showed just T wave abnormalities. At age 49, it fulfilled SV1 + RV5 or 6>35 mm with strain pattern. At age 52, echocardiography revealed definite left ventricular (LV) hypertrophy, and abnormally increased mitochondria were shown in biopsied endomyocardial specimens. He was diagnosed as having developed hypertrophic cardiomyopathy associated with the mutation. However, at age 54, SV1 and RV5,6 voltages were decreased, and echocardiography showed diffuse decreased LV wall motion and LV dilatation. Because he had mitochondrial diabetes, the patient's heart rapidly developed hypertrophic cardiomyopathy, and then it seemed to be changing to a dilated LV with systolic dysfunction. Rapid progression of cardiomyopathy can occur in mitochondrial diabetes.
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PMID:Rapid progression of cardiomyopathy in mitochondrial diabetes. 1008 76

We analyzed mitochondrial DNA (mtDNA) from 7 patients in four families with adult onset limb-girdle type mitochondrial myopathy to clarify their genetic background. The patients, 2 men and 5 women, showed common clinical features, characterized by isolated skeletal myopathy, high serum creatine kinase level, ragged-red fibers and cytochrome c oxidase-defective fibers. Analysis of muscle biopsy specimens indicated that cytochrome c oxidase activity was decreased relative to that of citrate synthase in 5 of the 7 patients. Southern blotting and direct sequence analyses showed an A-to-G homoplasmic transition at np8291 and intergenic COII/tRNA (Lys) 9bp deletion in all patients. This substitution was detected in only 2 of 600 control individuals including healthy subjects and patients with other neuromuscular disorders; these 2 individuals had diabetes mellitus and myotonic dystrophy, respectively. Consequently, the mtDNA transition at np8291 was a rare polymorphism. However, the 7 patients we studied had identical clinical, pathological, biochemical, and genetic features. Therefore, limb-girdle type mitochondrial myopathy with this rare polymorphism may form a subgroup of adult onset mitochondrial myopathy.
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PMID:Adult onset limb-girdle type mitochondrial myopathy with a mitochondrial DNA np8291 A-to-G substitution. 1031 90

Type 2 (non-insulin dependent) diabetes mellitus may be inherited along the maternal line and a variety of mitochondrial DNA (mtDNA) variants have been implicated in the pathogenesis. We have previously reported mutations in five regions of the mitochondrial genome which encompass 11 of the 22 tRNA genes. Now we employ the technique of single stranded conformational polymorphism (SSCP) analysis to investigate a further 6 regions of the mitochondrial genome, covering the remaining 11 tRNA genes in 40 patients with Type 2 diabetes and 30 racially-matched normal controls. A variety of homoplasmic mutations were detected in patients with diabetes and these will be of value in further population association studies.
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PMID:Mitochondrial DNA variations in patients with Type 2 (non-insulin dependent) diabetes mellitus and a Welsh control population. Mutation in brief no. 239. Online. 1033 99


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