Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with histologically proven mitochondrial myopathy with ophthalmoplegia (OMM), 6 of them nondiabetic, 1 affected by diabetes mellitus (DM), were submitted to a study of glucose tolerance and of insulin receptors on peripheral mononuclear cells and cultured skin fibroblasts. The diabetic patient, who had the typical features of the Kearns-Sayre syndrome (KSS) and deleted muscle mitochondrial DNA (mtDNA) presented a low insulin secretion rate under physiological stimuli (intravenous glucose and glucagon) whereas the insulin receptor parameters were found normal. The other patients showed a normal glucose tolerance and normal insulin receptors. Our data support the hypothesis that insulin receptors are not involved in the pathogenesis of DM associated with mitochondrial encephalomyopathies, in contrast to other neuromuscular inherited disorders. The clinical and biological features of DM presented by our KSS patient show normal insulin receptor parameters in spite of a defective insulin secretion, possibly depending on mitochondrial dysfunction.
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PMID:Normal insulin receptors in mitochondrial myopathies with ophthalmoplegia. 261 64

A 20-year-old woman with Kearns-Sayre syndrome (KSS) suddenly experienced two episodes of diabetic coma. She was studied to determine whether diabetes mellitus (DM) resulted from insulin resistance or from an insulin secretion abnormality, using the euglycemic glucose clamp technique and the glucagon tolerance test. She had a deficiency of insulin secretion from beta cells. It is important to recognize in practice the onset of DM in patients with mitochondrial myopathy. We would suggest that a genetic linkage or mitochondrial dysfunction may be responsible for the association of both disease states.
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PMID:Diabetes mellitus in Kearns-Sayre syndrome. 328 50

We report a 28-year-old young male with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) presenting with two previous episodes of stroke-like manifestation, lactic acidosis and mitochondrial cardiomyopathy. He was also affected with insulin-dependent diabetes mellitus (IDDM), as diagnosed by the experience of diabetic ketoacidosis (DKA), and dependence on insulin therapy. On admission, the serum lactate level was found to be increased to 5.4 mmol/l, and plasma glucose level to 7.9 mmol/l with haemoglobin A1c 8.4%, while he was using insulin 26-30 units per day. Physical examination revealed a short stature male of height of 150 cm and weight of 49 kg. Mild mental retardation with bilateral sensorineural hearing impairment was observed. After glucagon stimulation, C-peptide levels rose from 0.46 nmol/l to 0.53 nmol/l, indicative of impaired insulin secretion. Anti-glutamate decarboxylase (anti-GAD) antibody was positive. In addition, human leucocyte associated antigen (HLA) typing showed DR3 and DR4, suggesting the strong contribution of autoimmunity to the pathogenesis of IDDM in this patient. Moreover, the result of a treadmill exercise test was positive due to inferior wall myocardial ischaemia. Cardiac catheterization and endomyocardial biopsy disclosed a normal coronary angiogram and confirmed the diagnosis of mitochondrial cardiomyopathy. Molecular genetic analysis of his family revealed a sporadic occurrence of mitochondrial DNA (mtDNA) mutation at base pair (bp) 3243. The degree of heteroplasmy of mtDNA mutation from a total of 19 passages of skin-derived fibroblasts from this patient showed a slightly downward trend. This extremely rare case of sporadic MELAS syndrome with autoimmune IDDM harbouring mtDNA mutation highlights the possible pathogenetic role of mtDNA mutations in autoimmune disease.
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PMID:Autoimmune IDDM in a sporadic MELAS patient with mitochondrial tRNA(Leu(UUR)) mutation. 982 17

We report the unusual features of a female patient who had MELAS-specific A3243G mutation in mitochondrial DNA (mtDNA) and diabetes mellitus (DM). The patient showed mitochondrial myopathy, encephalopathy, lactic acidosis, and deafness but lacked the stroke-like episode. Acute hyperglycemia was noted after one attack of status epilepticus. Molecular genetic analysis demonstrated a heteroplasmic A3243G point mutation in the mtDNAs of muscle, blood cells and hair follicles. Glucagon stimulation test exhibited marked depression of pancreatic beta-cell function. However, in a further study neither this mutation, nor MELAS syndrome or DM, was found in all of her maternal relatives. A series of follow-up studies for beta-cell function also showed gradual improvement. The pedigree study led us to believe that this A3243G mutation arose from the germ line cells or occurred later in somatic tissues of the patient. We also suggest that the A3243G mutation of mtDNA may elicit the pathogenesis of a subtype of DM. Nevertheless, environmental stress may be another important factor for provocation of the disease.
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PMID:Absence of maternal A3243G mtDNA mutation and reversible hyperglycemia in a patient with MELAS syndrome. 1066 Jan 56