A high carbohydrate diet does not induce hyperglycaemia in a mitochondrial glycerol-3-phosphate dehydrogenase-deficient mouse.
OBJECTIVE
The electrons of the glycolysis-derived reduced form of NADH are transferred to mitochondria through the NADH shuttle system. There are two NADH shuttles: the glycerol phosphate and malate-aspartate shuttle. Mice with a targeted disruption of mitochondrial glycerol-3-phosphate dehydrogenase, a rate-limiting enzyme of the glycerol phosphate shuttle, are not diabetic and have normal islet glucose-induced secretion. In this study, we analyzed if environmental factors, such as a high carbohydrate diet could contribute to the development of Type 2 diabetes mellitus in mice with a specific defective genetic background.


METHODS
The mice were fed with a high carbohydrate diet for 1 and 6 months, and several biochemical parameters were analysed. The mitochondrial respiratory activity was assayed by polarography; and the islet function was studied by islet perifusion and pancreas perfusion.


RESULTS
The high carbohydrate diet induced hyperglycaemia, hyperinsulinaemia, and islet hyperplasia in the wild-type and heterozygote mice. Activity of the respiratory chain complex I also increased in these mice. In contrast, these effects were not observed in the null mice fed with the diet; in addition, these null mice had an increased insulin sensitivity compared to wild-type mice.


CONCLUSIONS
The phenotype of the mice with an impairment of NADH shuttles does not worsen when fed a high carbohydrate diet; moreover, the diet does not compromise islet function.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D019069:Cell Respiration / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005993:Glycerolphosphate Dehydrogenase / Q000172:deficiency*; D006943:Hyperglycemia / Q000209:etiology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology; D013997:Time Factors
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D008055:Lipids; D005993:Glycerolphosphate Dehydrogenase