Diabetologia: The lack of functional nicotinamide nucleotide transhydrogenase only has a moderate effect on the impairment of glucose tolerance and glucose-stimulated insulin secretion

Purpose/Assumption: Nicotinamide nucleotide transhydrogenase (NNT) is involved in the production of mitochondrial NADPH, and its spontaneous inactivating mutation (Nnt ^Tr [Tr, truncation]) is generally considered to be the glucose tolerance of C57BL/6J and C57BL/6N mice The main reason for the decrease
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However, the effect of this mutation on glucose tolerance remains controversial

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Nicotinamide nucleotide transhydrogenase (NNT) is involved in the production of mitochondrial NADPH, and its spontaneous inactivating mutation (Nnt ^Tr [Tr, truncation]) is generally considered to be the main cause of impaired glucose tolerance in C57BL/6J and C57BL/6N mice

^{WT/Tr Tr}

Results: The Nnt genotypes and genetic backgrounds of various types of mice were determined
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In C57BL/6N and C57BL/6J islets, N5-WT is compared with N5-Tr islets, N5-WT and N5-Tr islets have an effect on mitochondria (but not cytoplasm) E _GSH and NAD(P)H autofluorescence glucose The regulatory effect was significantly enhanced, confirming the role of NNT in mitochondrial redox regulation

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_GSH

Figure 1 The effect of glucose and FCCP on the oxidation of pancreatic islet mitochondria and cytoplasmic glutathione in female N5-WT and N5-Tr mice
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Two days after infection with Ad-mt-GRX1-roGFP2 (a, b) or ad GRX1-roGFP2 (c), the islets with various glucose concentrations (Gn=nmmol/l glucose), 15μmol/l H2O2 or 10μmol/l FCCP

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Figure 1 The effect of glucose and FCCP on the oxidation of pancreatic islet mitochondria and cytoplasmic glutathione in female N5-WT and N5-Tr mice

Figure 2 The effect of NNT on the glucose tolerance of female mice

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Figure 2 The effect of NNT on the glucose tolerance of female mice
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Table AUC of the six types of mice tested in this study during IPGTT

Table AUC of the six types of mice tested in this study during IPGTT

Conclusion: Although our results confirm the importance of NNT in the regulation of mitochondrial redox state by glucose, they significantly weaken the role of NNT in GSIS and glucose tolerance changes in C57BL/6J and C57BL/6N mice

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Although our results confirmed the importance of NNT in the regulation of mitochondrial redox status by glucose, they significantly weakened the role of NNT in GSIS and glucose tolerance changes in C57BL/6J and C57BL/6N mice

Close AF, Chae H, Jonas JC, The lack of functional nicotinamide nucleotide transhydrogenase only moderately contributes to the impairment of glucose tolerance and glucose-stimulated insulin secretion in C57BL/6J vs C57BL/6N mice.

Diabetologia 2021 Aug 27

The lack of functional nicotinamide nucleotide transhydrogenase only moderately contributes to the impairment of glucose tolerance and glucose-stimulated insulin secretion in C57BL/6J vs C57BL/6N mice.
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