Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
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.
 ...
PMID:Diabetes mellitus in Kearns-Sayre syndrome. 328 50

Mitochondrial DNA (mtDNA) mutations are associated with diabetes mellitus but their role in the onset of hyperglycaemia is unclear. A patient presented with diabetes requiring insulin therapy at the age of 7 years, followed by diagnosis of Kearns-Sayre syndrome (KSS). Beta-cell function was absent at age 19 years as shown by lack of glucose-stimulated C-peptide secretion. Following development of a cardiac conduction defect the patient died aged 21 years. Analysis of mtDNA in blood and several tissues revealed related re-arranged deletions, duplications and deletion dimers in addition to normal mtDNA with the highest levels of duplications in kidney and blood. Pancreatic tissue from the KSS patient was compared with tissue from an insulin-dependent diabetic patient with a similar clinical history of diabetes. Islets in KSS were small, regular in shape and contained predominantly glucagon-containing cells with no evidence of beta cells. In comparison, a small number of beta cells were present in some of the larger more irregularly-shaped islets from the insulin-dependent diabetic patient. These data together suggest that in KSS the loss of beta cells at the onset of diabetes is less disruptive to islet architecture: a small proportion of beta cells or their gradual destruction over a long period would allow retention of islet shape. Abnormal function of the re-arranged mtDNA could affect both development and function of pancreatic islet cells since glucose-stimulated insulin secretion is energy dependent.
 ...
PMID:Mitochondrial DNA, diabetes and pancreatic pathology in Kearns-Sayre syndrome. 755 92