Linking mitochondrial function to diabetes mellitus: an animal's tale.

Diabetes mellitus is one of the most common genetic diseases that afflicts humans. It is not a single disease but a collection of diseases having in common an abnormal glucose-insulin relationship and a dysfunctional regulation of glucose homeostasis. Of interest is the diabetic state that results when the mitochondrial genome mutates.

Mitochondrial gene expression: influence of nutrients and hormones.

Mitochondrial gene transcription research has exploded over the last decade. Nuclear-encoded proteins, nutrients, and hormones all work to regulate the transcription of this genome. To date, very few of the transcription factors have been shown to have negative effects on mitochondrial gene expression, although there are likely conditions where such downregulation may occur.

Nutrient-gene interactions: dietary vitamin A and mitochondrial gene expression.

The BHE/Cdb rat is a model for mitochondrial diabetes due to a mutation in the ATPase 6 gene. These rats require more dietary vitamin A to optimize mitochondrial function than do normal Sprague-Dawley rats. To determine a possible mechanism for this effect, cultured hepatocytes and hepatic tissues were studied.

Nutrient-gene interactions in mitochondrial function: vitamin A needs are increased in BHE/Cdb rats.

The BHE/Cdb rat has a maternally inherited mutation in the ATPase 6 mitochondrial gene that associates with impaired oxidative phosphorylation (OXPHOS) and glucose intolerance. A longevity study revealed that feeding an egg-rich (vitamin A-rich) diet delayed the onset of impaired glucose tolerance. Two experiments were conducted to test the hypothesis that BHE/Cdb rats require more dietary vitamin A than normal rats.

Regulation of mitochondrial gene expression by retinoids.

Several nuclear hormone receptors have been localized to the mitochondrial compartment. Evidence supports the hypothesis that these receptors directly regulate mitochondrial transcription. Retinoic acid has also been shown to regulate mitochondrial transcription and function.