Vitamin B12 and transcobalamin in bovine milk: Genetic variation and genome-wide association with loci along the genome.

In human nutrition, bovine milk is an essential source of bioavailable vitamin B12 and B12-binding proteins, including transcobalamin. In this study, we estimated genetic parameters for milk content of vitamin B12 and transcobalamin using milk samples from 341 and 663 Danish Holstein cows, respectively. Additionally, we conducted whole-genome association analysis to identify SNP and genes associated with vitamin B12 and transcobalamin. Our results indicated moderate to high heritability for vitamin B12 (0.37 ± 0.18) and transcobalamin (0.61 ± 0.13) content in the Danish Holstein. With a significance threshold of -log10 P-value > 5.87, significant associations were detected between SNP in Bos taurus autosome (BTA)17 and the log-transformed transcobalamin content of milk; no significant association was detected for vitamin B12. The significant region in BTA17 was imputed to full sequence for further fine mapping, and the SNP with the most significant associations to transcobalamin were assigned to the transcobalamin 2 (TCN2) gene.

Chronic Exposure to Proline Causes Aminoacidotoxicity and Impaired Beta-Cell Function: Studies In Vitro.

BACKGROUND: Pancreatic islet-cell dysfunction is a hallmark in the development of diabetes, but the reasons for the primary ß-cell defect are still elusive. Elevated circulating proline levels have been found in subjects with insulin resistance, obesity, and type 2 diabetes. Therefore, we assessed ß-cell function, gene expressions, and cell death after long-term exposure of pancreatic ß-cells to excess proline in vitro. METHODS: Isolated mouse islets and INS-1E cells were incubated with and without excess proline. After 72 h, we examined: (1) ß-cell function, including basal insulin secretion (BIS) and glucose-stimulated insulin secretion (GSIS), (2) transcription factors related to insulin gene expression and enzymes involved in the tricarboxylic acid cycle and cholesterol biogenesis, (3) cellular triglycerides (TG) and cholesterol content, (4) the death of INS-1E cells and 3H thymidine incorporation, and (5) protein expression of INS-1E cells in response to proline by proteomics. RESULTS: We found that high doses of proline increased BIS and decreased GSIS in both isolated mouse islets and INS-1E cells. MafA, insulin 1, and the cytochrome c oxidase subunit VIa polypeptide 2 mRNA expressions were all downregulated, indicating that proline impaired insulin gene transcription and mitochondrial oxidative phosphorylation. In contrast, mevalonate decarboxylase gene expression was upregulated, and simultaneously, cholesterol content in INS-1E cells was enhanced. Protein profiling of INS-1E cells revealed that cytosolic non-specific dipeptidase and α enolase were differentially expressed. CONCLUSIONS: Our results indicate that proline-induced insulin transcription and mitochondrial oxidative phosphorylation impairment may contribute to the ß-cell dysfunction observed in type 2 diabetes. Caution should be applied in interpreting the pathophysiological role of proline since very high proline concentrations were used in the experiments.