Mitochondrial diabetes mellitus: a review

Kd, Gerbitz; Jm, van den Ouweland; Maassen, J. Antonie; Jaksch, Michaela

doi:10.1016/0925-4439(95)00036-4

Cited by 197 publications

(101 citation statements)

References 42 publications

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“…Another cause of IDDM that is relevant to our present proposal is deficient mitochondrial function of beta cells due to lesions in mitochondrial DNA [3,4]. Autoimmune IDDM can occur either acutely in childhood, or gradually as latent autoimmune diabetes of adults [5].…”

mentioning

confidence: 77%

“…Indeed, the increase of intracellular ATP which is stimulated by a high blood glucose level is the signal for insulin release via a block of potassium channels in the plasma membrane of the beta cells [32][33][34]. The critical role of oxphos in providing this ATP signalling is clearly illustrated by the high susceptibility of beta cells to energy deficits consequent to mitochondrial gene mutations [3,4], now recognized as the disease entity 'mitochondrial diabetes' [4]. We consider that various toxins, febrile states or even sugar overload can induce a deficiency in mitochondrial oxphos similar to that resulting from inherited mutations, albeit only transiently.…”

Section: Critical Effects Of Oxidative Phosphorylation Deficiencymentioning

confidence: 99%

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The GABA network and the pathogenesis of IDDM

Esposti

Mackay

1997

Diabetologia

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mentioning

confidence: 77%

Section: Critical Effects Of Oxidative Phosphorylation Deficiencymentioning

confidence: 99%

The GABA network and the pathogenesis of IDDM

Esposti

Mackay

1997

Diabetologia

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“…In addition to the 13 polypeptides of the respiratory chain enzyme complexes, the mitochondrial DNA (mtDNA) encodes 22 transfer RNAs and two ribosomal RNAs [58±61]. A mutational hot spot seems to be the tRNA Leu(UUR) [61,66].…”

Section: Role Of Mitochondrial Dna In Insulin Secretionmentioning

confidence: 99%

“…Mitochondrial diabetes accounts for approximately 1 to 2 % of all cases of diabetes [58,66]. The disease is maternally inherited due to the transmission mode of mtDNA.…”

Section: Role Of Mitochondrial Dna In Insulin Secretionmentioning

confidence: 99%

“…Patients with the mutation in position bp3243 in the tRNA Leu(UUR) gene have impaired insulin secretion during an oral glucose tolerance test. The impairment was found to be most pronounced in diabetic patients also suffering from deafness [66]. To gain further insight into the function of the mitochondria that carry DNA mutations, clonal cell lines (cybrids) have been established which harbour these mitochondria [67].…”

Section: Role Of Mitochondrial Dna In Insulin Secretionmentioning

confidence: 99%

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Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in Type II diabetes

Wollheim¹

2000

Diabetologia

176

149

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In previous lectures, Claude Bernard's many scientific contributions have been highlighted. Among others he suggested in 1850 that the liver stores glucose and 7 years later, in 1857, he finally isolated glycogen [2]. Before that, in 1849, Claude Bernard reported his ªPiqßre sucrØeº to the SociØtØ de Biologie, Paris [3]. In analogy to his experiments in which stimulation of the fifth cranial nerve caused saliva secretion, he assumed that stimulation of the vagus nerve would elicit glucose secretion from the liver. In unanaesthetised rabbits and dogs, the pricking of the bottom of the fourth ventricle resulted in pronounced hyperglycaemia and glucosuria within 20 min. The ªdiabetesº was transient and disappeared after a few hours. He later showed that this effect was mediated, not by the vagus, but by sympathetic nerves. His discovery of glycogen made Claude Bernard the true father of Diabetologia (2000) AbstractInsulin is stored in secretory granules in the beta-cell and is secreted by exocytosis. This process is precisely controlled to achieve blood glucose homeostasis. Many forms of diabetes mellitus display impaired glucose-induced insulin secretion. This has been shown to be the primary cause of the disease in the various forms of maturity-onset diabetes of the young (MODY) and has also been implicated in adult-onset Type II (non-insulin-dependent) diabetes mellitus. Glucose generates ATP and other metabolic coupling factors in the beta-cell mitochondria. By plasma membrane depolarisation ATP promotes Ca 2+ influx, which raises cytosolic Ca 2+ and triggers insulin exocytosis. Through hyperpolarisation of the mitochondrial membrane glucose also increases the Ca 2+ concentration in the mitochondrial matrix activating Ca 2+ -sensitive dehydrogenases in the tricarboxylic acid cycle. The resulting generation of glutamate participates in Ca 2+ -stimulated exocytosis. Mitochondrial DNA (mtDNA) encodes some of the polypeptides of the respiratory chain enzyme complexes. Mutations in mtDNA lead to maternally inherited diabetes mellitus characterised by impaired insulin secretion. The impact of altered mtDNA on insulin secretion has been shown in mtDNA-deficient beta-cell lines which have lost glucose-stimulated insulin secretion but retain a Ca 2+ -induced insulin secretion. A cellular model of MODY3 expressing dominant-negative hepatocyte nuclear factor-1a (HNF-1a) also displayed deletion of glucose-induced but not Ca 2+ -induced insulin secretion. Reduced mitochondrial metabolism explains this secretory pattern. Thus, genetically manipulated beta-cell lines are essential tools in the investigation of the molecular basis of beta-cell dysfunction in diabetes and should explain the role of other transcription factors in the disease. [Diabetologia (2000) 43: 265±277]

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Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness

et al. 1998

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The mitochondrial mutation A3243G has been shown to be associated with a syndrome of diabetes mellitus and sensorineural hearing loss. Using a solid‐phase‐based sequencing method we have investigated the relation between the proportion of mutant mitochondrial genomes and the time of disease onset among members of three families where the mutation segregates. A striking association was observed between the level of heteroplasmy and time of onset of disease, particularly hearing loss. Accordingly, this syndrome shares features of diseases caused by dynamic mutations in that variable transmission of the level of heteroplasmy between generations influences disease severity. Hum Mutat 12:52–58, 1998. © 1998 Wiley‐Liss, Inc.

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Mitochondrial diabetes mellitus: a review

Cited by 197 publications

References 42 publications

The GABA network and the pathogenesis of IDDM

The GABA network and the pathogenesis of IDDM

Beta-cell mitochondria in the regulation of insulin secretion: a new culprit in Type II diabetes

Level of heteroplasmy for the mitochondrial mutation A3243G correlates with age at onset of diabetes and deafness

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