Integrated analysis of gene modulation profile identifies pathogenic factors and pathways in the liver of diabetic mice.

PURPOSE: Type-2 diabetes mellitus (T2D) is a metabolic disorder that can progress to a serious chronic disease and frequently develops in obese individuals in association with various pathogenic complications that shorten the lifespan of these patients. The liver is an important organ regulating lipid metabolism, which is damaged in both obesity and T2D; however, the specific pathways involved in these pathogenic effects remain unclear. Establishing a suitable animal model that effectively mimics the human biological condition is a critical factor to allow for precise identification of T2D-related genes. METHODS: The KK.Cg-Ay mouse strain is one such model that has offered insight into obesity-related T2D pathogenesis. To comprehensively assess the association between obesity and T2D, in the present study, we performed microarray analysis on liver tissue samples of KK.Cg-Ay and KK-α/α wild-type mice to examine differences in gene expression and methylation patterns and their related biological processes and pathways. RESULTS: We found that inflammation accompanied by abnormal lipid metabolism led to the spontaneous mechanism of obesity-induced diabetes, resulting in differential expression of some genes related to the terms of insulin resistance and glucose tolerance. Surprisingly, disruption of steroid biosynthesis strongly facilitated the diabetic pathogenesis. To support these findings, we highlighted some candidate genes and determined their relationships in biological networks of obesity-induced T2D. CONCLUSION: These findings provide valuable reference data that can facilitate further detailed investigations to elucidate the pathogenic mechanism of obesity-induced diabetes in mice, which can be associated with the human condition to inform new prevention and treatment strategies.

Autophagy and its link to type II diabetes mellitus.

Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and failure of producing insulin on pancreatic beta cells. In T2DM, autophagy is not only providing nutrients to maintain cellular energy during fasting, but also removes damaged organelles, lipids and miss-folded proteins. In addition, autophagy plays an important role in pancreatic beta cell dysfunction and insulin resistance. In this review, we summarize the roles of autophagy in T2DM.

Current concepts regarding developmental mechanisms in diabetic retinopathy in Taiwan.

Diabetic retinopathy (DR) is one of the most feared complications of diabetes and is a leading cause of acquired blindness in working adults. The prevalence of undiagnosed diabetes in Taiwan is about 4%, and the annual incidence of T2D (Type 2 Diabetes) in Taiwan is 1.8% following the 1985 WHO criteria. Multiple mechanisms have been shown in T2DR with some signaling pathways, including the polyol pathway, PKC pathway, AGEs pathway, and MAPK pathway. However, the cause of vision loss in diabetic retinopathy is complex and remains incompletely understood. Herein, we try to fully understand the new concepts regarding hyperglycemia-induced biochemical pathways contributing to DR pathophysiology. Our work may be able to provide new strategies for the prevention and treatment of diabetic vascular complications.

Copy-number variations in hepatoblastoma associate with unique clinical features.

PURPOSE: Hepatoblastoma is a rare childhood liver malignancy with limited relevant cytogenetic data. This study aimed to discover common genomic copy-number variations (CNVs) in subjects with hepatobalstoma and its relevance to the clinical course. METHODS: Gene copy-number was systemically rated by high-resolution comparative genomic hybridization (CGH) DNA oligonucleotide microarray. The study group consisted of 12 children (7 males and 5 females) with hepatoblastoma and another 20 healthy individuals (10 males and 10 females) as controls. The influence of recurrent CNVs on clinical outcomes was analyzed. RESULTS: Four highly recurrent CNVs were identified in these 12 hepatoblastoma children after comparison with controls, including a gain on 1p13.3 (n = 3, 25%) and losses on 5p15.33 (n = 4, 33.3%), 16q12.2 (n = 4, 33.3%), and 19q13.42 (n = 3, 25%). The most prevalent sites of genomic deletion were 5p15.33 and 16q12.2. Zinc finger, DHHC-type containing 11 (ZDHHC11) and DHHC-type containing 11B (ZDHHC11B) were mapped to 5p15.33, which was associated with a lower rate of survival with native liver (p = 0.03). The carboxylesterase 4-like (CES4) gene that mapped to 16q12.2 was associated with smaller tumor size at presentation. CONCLUSIONS: Deletions of 5p15.33 (33.3%) and 16q12.2 (33.3%) are the most frequent hepatoblastoma-related events in our patient group with 5p15.33 microdeletion as a potential biomarker for the fate of survival with native liver.