Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study provides a compact overview on the most common form of the maternally inherited diabetes and deafness syndrome (MIDD) that associates with an A-G mutation in mitochondrial DNA at position 3243 in the tRNA(Leu,UUR) gene. The pathobiochemistry and pathophysiology is discussed. The mutation leads predominantly to a reduced insulin secretion by beta cells in response to glucose stimulation, however, without marked involvement of autoimmune processes as seen in type 1 diabetes mellitus. The underlying biochemical mechanism leading to beta cell dysfunction is discussed. Furthermore, the clinical presentation of the disease is summarized as are the methods to detect the A3243G mutation, particular in view of the often low levels of heteroplasm of the A3243G mutation.
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PMID:Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. 1211 79

Fulminant type 1 diabetes exhibits distinct clinical futures from "classic" autoimmune type 1 diabetes. Although the etiology of fulminant type 1 diabetes is not fully elucidated, class II HLA could contribute to the development of fulminant type 1 diabetes. In Japanese patients with "classic" type 1 diabetes, DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 are major susceptible HLA-DR-DQ haplotypes, whereas DRB1*1502-DQB1*0601 and DRB1*1501-DQB1*0602 are protective. In contrast, only DRB1*0405-DQB1*0401, but not DRB1*0901-DQB1*0303, is a susceptible haplotype in fulminant type 1 diabetes. In addition, neither DRB1*1502-DQB1*0601 nor DRB1*1501-DQB1*0602 are protective haplotypes in fulminant type 1 diabetes. In genotypic combination analysis, the homozygotes of DRB1*0405-DQB1*0401 are associated with both fulminant type 1 diabetes and "classic" type 1 diabetes, whereas the homozygotes of DRB1*0901-DQB1*0303 are associated with only "classic" type 1 diabetes. These findings suggest a different contribution of class II HLA in the mechanisms of beta cell damage between fulminant and "classic" type 1 diabetes. To further address the pathogenesis of fulminant type 1 diabetes, HNF-1alpha gene mutation and mutation of the mitochondrial DNA were analyzed in patients with fulminant type 1 diabetes admitted to our department during the period from 1990 to 2000. Neither mutations of HNF-1alpha gene nor A-to-G mutation at nucleotide position 3,243 of the mitochondrial tRNA(LEU(UUR)) gene were identified in these patients. These results suggest that the HNF-1alpha gene mutation and mutation of the mitochondrial DNA are not likely associated with diabetic patients with fulminant clinical symptoms at disease onset. In this article we will summarize the current findings on the genetics of Japanese patients with fulminant type 1 diabetes.
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PMID:Genetics of fulminant type 1 diabetes. 1713 May 28

Maternally inherited diabetes with deafness (MIDD) is a rare, monogenic form of diabetes mellitus caused by mutations in the mitochondrial genome, the most frequent being the A3243G substitution of the tRNA(Leu) gene. We screened 520 individuals with type 2 diabetes mellitus and 45 probands from families with a clinical picture of maturity onset diabetes of the young (MODY) using restriction fragment length polymorphism. One carrier of the mutation being investigated was found in a proband from a MODY family. The patient was a 20 year-old woman, diagnosed at the age of 16 years as having type 1 diabetes mellitus. On entry to the study, she was treated by a multiple daily injection regimen (MDI) with regular human insulin and human NPH insulin. Typical extra-pancreatic symptoms of MIDD were present, such as macular pattern dystrophy and mild bilateral sensory hearing loss. Additionally, the patient presented abdominal obesity (BMI 32.0), an uncommon feature in monogenic insulin secretion defects, including MIDD. To facilitate weight loss, the diabetes treatment was modified. Since metformin treatment is considered to be contraindicated in MIDD because of the increased risk of lactic acidosis, we used insulin analogues (aspart and detemir) in an MDI regimen and hypocaloric diet. This resulted in a 6.3 kg weight reduction (BMI 27.4) and normalization of HbA1c level (from 7.2 to 6.1 %) during a three-month follow-up. On the basis of this case, we suggest that an MDI regimen with insulin analogues may be a preferred therapeutic option in some rare clinical situations, such as MIDD associated with obesity.
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PMID:Maternally inherited diabetes with deafness and obesity: body weight reduction response to treatment with insulin analogues. 1748 45

A 28-year-old man presented with multiple flexion contractures of hands and feet, deafness, diabetes mellitus and obstructive nephropathy because of bilateral ureterovesicular stricture. Other prominent clinical findings were short stature, bilateral proptosis, multiple freckles and sacralisation of LS. In order to investigate the role of mitochondrial mutations in various clinical manifestations observed in this patient, we performed mutation screening of 1.6 kb mtDNA around the tRNA (Leu(UUR)) part of 16SrRNA and the ND1 gene. No mutation was present at position 3243 which is associated with diabetes mellitus and deafness. A new point mutation (A/G) at position 4093 of the ND1 gene was found. In conclusion, we found a novel mitochondrial mutation in a patient with diabetes and deafness. This mutation has not been reported before and is the first mutation described in the ND1 gene which is related to insulin dependent diabetes mellitus and deafness and could be specific to the Iranian population. All other unusual clinical findings in this patient can be attributed to the presence of this new mutation.
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PMID:A new mitochondrial mutation in a patient with diabetes mellitus, deafness, hydronephrosis and joint contractures. 1918 93

Diabetes induces oxidative stress, DNA damage and alters several intracellular signaling pathways in organ systems. This study investigated modulatory effects of Trans-Resveratrol on type 1 diabetes mellitus (T1DM)-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase (PARP) signaling in rat testis. Trans-Resveratrol administration (5mg/kg/day, ip) to Streptozotocin-induced T1DM adult male Wistar rats from day 22-42 resulted in recovery of induced oxidative stress, abnormal spermatogenesis and inhibited DNA synthesis, and led to mitigation of 8-hydroxy-2'-deoxyguanosine formation in the testis and spermatozoa, and DNA double-strand breaks in the testis. Trans-Resveratrol aggravated T1DM-induced up-regulation of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 expression; however, it did not modify the up-regulated total PARP and down-regulated PARP1 expressions, but recovered the decreased SirT1 (Sirtuin 1) levels in T1DM rat testis. Trans-Resveratrol, when given alone, reduced the poly (ADP-ribosyl)ation (pADPr) process in the testis due to an increase in PAR glycohydrolase activity, but when given to T1DM rats it did not affect the pADPr levels. T1DM with or without Trans-Resveratrol did not induce nuclear translocation of apoptosis-inducing factor and the formation of 50 kb DNA breaks, suggesting to the lack of caspase-3-independent cell death called parthanatos. T1DM with or without Trans-Resveratrol did not increase necrotic cell death in the testis. Primary spermatocytes, Sertoli cells, Leydig cells and intra-testicular vessels showed the expression of PARP pathway related proteins. In conclusion, Trans-Resveratrol mitigates T1DM-induced sperm abnormality and DNA damage, but does not significantly modulate PARP signaling pathway, except the SirT1 expression, in the rat testis.
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PMID:Effects of Trans-Resveratrol on hyperglycemia-induced abnormal spermatogenesis, DNA damage and alterations in poly (ADP-ribose) polymerase signaling in rat testis. 2768 54


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