ArticleDiabetologia2007
Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes.
Article in Diabetologia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 76 citations in OpenAlex.
- Nicotinamide nucleotide transhydrogenase deficiency and genetic susceptibility to high glucose-mediated peritoneal injury in mice.Physiological reports · 2025Article
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- Differences in lipid metabolism in acquired versus preexisting glucose intolerance during gestation: role of free fatty acids and sphingosine-1-phosphate.Lipids in health and disease · 2022Article
- Regulation of immune cell function by nicotinamide nucleotide transhydrogenase.American journal of physiology. Cell physiology · 2022Review
- Glucose-Stimulated Calcium Dynamics in Beta Cells From Male C57BL/6J, C57BL/6N, and NMRI Mice: A Comparison of Activation, Activity, and Deactivation Properties in Tissue Slices.Frontiers in endocrinology · 2022Article
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- Nicotinamide riboside has minimal impact on energy metabolism in mouse models of mild obesity.The Journal of endocrinology · 2021Article
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- Functions of Osteocalcin in Bone, Pancreas, Testis, and Muscle.International journal of molecular sciences · 2020Review
- E2f8 and Dlg2 genes have independent effects on impaired insulin secretion associated with hyperglycaemia.Diabetologia · 2020Article
- A genetic screen identifies Crat as a regulator of pancreatic beta-cell insulin secretion.Molecular metabolism · 2020Article
- Considerations and guidelines for mouse metabolic phenotyping in diabetes research.Diabetologia · 2018Review
- A Mouse Model of Beta-Cell Dysfunction as Seen in Human Type 2 Diabetes.Journal of diabetes research · 2018Article
- Absence of Nicotinamide Nucleotide Transhydrogenase in C57BL/6J Mice Exacerbates Experimental Atherosclerosis.Journal of vascular research · 2018Article
- Deletion of Protein Kinase D1 in Pancreatic β-Cells Impairs Insulin Secretion in High-Fat Diet-Fed Mice.Diabetes · 2018Article
- High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains.The Journal of endocrinology · 2017Article
- Cleavage Speed and Blastomere Number in DBA/2J Compared with C57BL/6J Mouse Embryos.Journal of the American Association for Laboratory Animal Science : JAALAS · 2017Article
- Attention to Background Strain Is Essential for Metabolic Research: C57BL/6 and the International Knockout Mouse Consortium.Diabetes · 2016Review
- Article
- Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2015Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulin hypersecretion may be an independent predictor of progression to type 2 diabetes. Identifying genes affecting insulin hypersecretion are important in understanding disease progression. We have previously shown that diabetes-susceptible DBA/2 mice congenitally display high insulin secretion. We studied this model to map and identify the gene(s) responsible for this trait.
methodsIntravenous glucose tolerance tests followed by a genome-wide scan were performed on 171 (C57BL/6 x DBA/2) x C57BL/6 backcross mice.
resultsA quantitative trait locus, designated hyperinsulin production-1 (Hip1), was mapped with a logarithm of odds score of 7.7 to a region on chromosome 13. Production of congenic mice confirmed that Hip1 influenced the insulin hypersecretion trait. By studying appropriate recombinant inbred mouse strains, the Hip1 locus was further localised to a 2 Mb interval, which contained only nine genes. Expression analysis showed that the only gene differentially expressed in islets isolated from the parental strains was Nnt, which encodes the mitochondrial proton pump, nicotinamide nucleotide transhydrogenase (NNT). We also found in five mouse strains a positive correlation (r2 = 0.90, p < 0.01) between NNT activity and first-phase insulin secretion, emphasising the importance of this enzyme in beta cell function. Furthermore, of these five strains, only those with high NNT activity are known to exhibit severe diabetes after becoming obese. CONCLUSIONS/
interpretationInsulin hypersecretion is associated with increased Nnt expression. We suggest that NNT must play an important role in beta cell function and that its effect on the high insulin secretory capacity of the DBA/2 mouse may predispose beta cells of these mice to failure.
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