Decreased mitochondrial gene expression in isolated islets of rats injected neonatally with streptozotocin

Welsh, Nils; Pääbo, Svante; Welsh, Michael

doi:10.1007/bf00400991

Cited by 29 publications

(11 citation statements)

References 42 publications

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“…Oxidative phosphorylation in the mitochondria is thought to be particularly crucial in insulin secretion in pancreatic beta cells [36] since the basic energy state of the cells is maintained in the form of adenosine triphosphate (ATP) by oxidative phosphorylation in the mitochondria. Streptozotocin has been shown to inhibit mitochondrial respiratory chain function and lead to inhibition of insulin production by the pancreatic beta cells, analogous to the mechanism in which chronic oxidative phosphorylation deficiency inhibits insulin production, thereby producing diabetes in rats [37], which suggests that pancreatic islets are also highly oxidative. These data together indicate that as inhibition of oxidative phosphorylation increases, mitochondrial ATP production declines until it falls below the minimum energy levels which are necessary for more oxidative tissues including beta cells to function.…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus carrying a mutation in the mitochondrial tRNALeu(UUR) gene

et al. 1995

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SummaryWe screened 214 Japanese NIDDM (noninsulin-dependent) diabetic patients with a family history of diabetes for mutations in the mitochondrial tRNA ~u(v~JR) gene using polymerase chain reactionrestriction fragment length polymorphism and direct sequencing. Six patients were identified as having an A to G transition at position 3243 (3243 mutation), but no patients were detected with a T to C transition at position 3271, in the mitochondrial tRNA Leu(uum gene. These two mutations were not present in 85 healthy control subjects. It was disclosed that the patients' mothers were also affected by diabetes mellitus in five of the six cases. In these six affected patients, the 3243 mutation shows variable phenotypes, such as the degree of multiple organ involvement, intrafamilial and interfamilial differences in disease characteristics, and the degree of the involvement of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) phenotype. Endocrinological examinations revealed that those diabetic patients with the 3243 mutation show not only beta-cell dysfunction, but also a defect in alphacell function, which is considered characteristic of diabetes with the 3243 mutation. When compared with 50 selected diabetic control subjects without the 3243 mutation, whose mothers, but not fathers, were found to have diabetes, it was established statistically that those with the 3243 mutation possess the following clinical characteristics; 1) the age of diabetes onset is lower, 2) they have lean body constitutions, and 3) they are more likely to be treated with insulin than control subjects. We suggest that diabetes with the 3243 mutation possesses phenotypes distinct from those in common forms of diabetes. [Diabetologia (1995) 38: 193-200]

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Section: Discussionmentioning

confidence: 99%

Diabetes mellitus carrying a mutation in the mitochondrial tRNALeu(UUR) gene

et al. 1995

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“…11 The mtDNA regulates oxidative phosphorylation and thus insulin secretion from pancreatic β-cells. 12 Decreased insulin secretion from pancreatic islets isolated from type 2 diabetic patients has been shown to be associated with induction of UCP2 and marked alteration of mitochondrial function and morphology. 13 In addition to the UCP, activity of mitochondrial aconitase, 14 glycerophosphate dehydrogense, 15 pyruvate carboxylase 15 and pyruvate dehydrogenase 16 was found to be significantly lower in diabetic islets.…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial proteome analysis reveals altered expression of voltage dependent anion channels in pancreatic β-cells exposed to high glucose

Ahmed¹,

Muhammed²,

Kessler³

et al. 2010

Islets

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“…Diabetes can be precipitated by exposure to mitochondrial poisons (37) and by downregulation of mitochondrial function in a mouse knockout (32), because ATP is critically important to both insulin production and release (2,33). Hence, insulin secretion is impaired in maternally inherited diabetes and/or deafness (MIDD) (34), caused by the 3243G:C point mutation of mtDNA (29).…”

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confidence: 99%