Dataset Information

Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.

ABSTRACT: There are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with mass spectrometry were used to determine changes in mRNA and protein expression in pancreatic and liver tissues of diabetic db/db mice in response to dietary selenate supplementation. Fasting blood glucose levels increased continuously in db/db mice administered placebo (DMCtrl), but decreased gradually in selenate-supplemented db/db mice (DMSe) and approached normal levels after termination of the experiment. Pancreatic islet size was increased in DMSe mice compared with DMCtrl mice, resulting in a clear increase in insulin production and a doubling of plasma insulin concentration. Genes that encode proteins involved in key pancreatic ?-cell functions, including regulation of ?-cell proliferation and differentiation and insulin synthesis, were found to be specifically upregulated in DMSe mice. In contrast, apoptosis-associated genes were downregulated, indicating that islet function was protected by selenate treatment. Conversely, liver fat accumulation increased in DMSe mice together with significant upregulation of lipogenic and inflammatory genes. Genes related to detoxification were downregulated and antioxidant enzymatic activity was reduced, indicating an unexpected reduction in antioxidant defense capacity and exacerbation of fatty liver degeneration. Moreover, proteomic analysis of the liver showed differential expression of proteins involved in glucolipid metabolism and the endoplasmic reticulum assembly pathway. Taken together, these results suggest that dietary selenate supplementation in db/db mice decreased hyperglycemia by increasing insulin production and secretion; however, long-term hyperinsulinemia eventually led to reduced antioxidant defense capacity, which exacerbated fatty liver degeneration.

SUBMITTER: Wang C

PROVIDER: S-EPMC4077766 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.

Wang Chaoqun C Yang Shulin S Zhang Ningbo N Mu Yulian Y Ren Hongyan H Wang Yefu Y Li Kui K

PloS one 20140701 7

There are conflicting reports on the link between the micronutrient selenium and the prevalence of diabetes. To investigate the possibility that selenium acts as a "double-edged sword" in diabetes, cDNA microarray profiling and two-dimensional differential gel electrophoresis coupled with mass spectrometry were used to determine changes in mRNA and protein expression in pancreatic and liver tissues of diabetic db/db mice in response to dietary selenate supplementation. Fasting blood glucose leve ...[more]

PMID: 24983750

Similar Datasets

Project description:Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient db/db mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and db/db mice received 4-phenylbutyric acid (4-PBA) (25 mg/kg/day) and saline by intraperitoneal injection every other day for 4 weeks. WT and db/db mice were given tail vein injections of 100 μL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old db/db mice, 16-week-old db/db mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mg/kg/day, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in db/db mice including cardiac hypertrophy and apoptosis in db/db mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in db/db mice through the ERS-MAPK10 signaling pathway in diabetic mice.

Dataset Information

Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.

Publications

Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets