Journal of Diabetes Investigation最新文献

Blood metabolomics profiling has emerged as a powerful approach for investigating metabolic diseases¹. Blood is readily accessible and contains metabolites derived from various physiological systems. Mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy offers an analytical platform for the comprehensive analysis of blood metabolites, including proteins, lipids, peptides, and glycans. Metabolites represent the end product of biological processes and are sensitive to environmental exposures. Thus, it is expected that the levels of metabolites could indicate a disease risk at an early stage. It is important to replicate and validate findings from untargeted metabolomics studies.

Tomofuji et al.² revealed the serum metabolite signatures of persons with type 2 diabetes mellitus with both diabetic retinopathy (DR) and diabetic kidney diseases (DKD) using a comprehensive untargeted metabolomics approach combining capillary electrophoresis time-of-flight mass spectrometry (CU-TOFMS) and liquid chromatography TOFMS². They compared the abundance of 364 metabolites between persons with type 2 diabetes mellitus with both DR and DKD (N = 141) and those without either DR or DKD (N = 159). They revealed that five metabolites including N-acetylneuraminic acid were associated with complications of type 2 diabetes in a Japanese population (cyclohexylamine, P = 4.5 × 10⁻⁶; 1,2-distearoyl-glycero-3-phosphocholine, P = 7.3 × 10⁻⁶; piperidine, P = 4.8 × 10⁻⁴; N-acetylneuraminic acid, P = 5.1 × 10⁻⁴; stearoyl ethanolamide, P = 6.8 × 10⁻⁴).

Ancel et al.³ reported the serum metabolite signatures of persons with type 2 diabetes mellitus with both diabetic retinopathy and diabetic kidney diseases with a comprehensive nontargeted metabolomics and lipidomics approach³. They compared the abundance of 563 metabolites between persons with type 2 diabetes mellitus with both DR and DKD (N = 53) and those without either DR or DKD (N = 61). They revealed that four metabolites including N-acetylneuraminate were associated with complications of type 2 diabetes mostly in European populations (methylguanidine, P < 0.001, 1.89 fold change; N-acetylneuraminate, P < 0.001, 1.73 fold change; arabinose, P < 0.001, 2.37 fold change; mevalolactone P < 0.001, 1.30 fold change), which is consistent with the results of Tomofuji et al. (Figure 1).

N-acetylneuraminic acid, also known as sialic acid, is one of the commonly distributed natural carbohydrates, and it is also a basic component of many glycopeptides, with a role in monocyte/macrophage migration through binding to the Rho A and Cdc42 and activating the Rho/Rho-associated coiled-coil containing protein kinase

Elucidating the molecular mechanism of autophagy was a landmark in understanding not only the physiology of cells and tissues, but also the pathogenesis of diverse diseases, including diabetes and metabolic disorders. Autophagy of pancreatic β-cells plays a pivotal role in the maintenance of the mass, structure and function of β-cells, whose dysregulation can lead to abnormal metabolic profiles or diabetes. Modulators of autophagy are being developed to improve metabolic profile and β-cell function through the removal of harmful materials and rejuvenation of organelles, such as mitochondria and endoplasmic reticulum. Among the known antidiabetic drugs, glucagon-like peptide-1 receptor agonists enhance the autophagic activity of β-cells, which might contribute to the profound effects of glucagon-like peptide-1 receptor agonists on systemic metabolism. In this review, the results from studies on the role of autophagy in β-cells and their implication in the development of diabetes are discussed. In addition to non-selective (macro)autophagy, the role and mechanisms of selective autophagy and other minor forms of autophagy that might occur in β-cells are discussed. As β-cell failure is the ultimate cause of diabetes and unresponsiveness to conventional therapy, modulation of β-cell autophagy might represent a future antidiabetic treatment approach, particularly in patients who are not well managed with current antidiabetic therapy.