Minyan Liu

Impaired autophagic function in rat islets with aging

Type 2 diabetes is characterized by a deficit in β-cell function and mass, and its incidence increases with age. Autophagy is a highly regulated intracellular process for degrading cytoplasmic components, particularly protein aggregates and damaged organelles. Impaired or deficient autophagy is believed to cause or contribute to aging and age-related disease. Autophagy may be necessary to maintain structure, mass, and function of pancreatic β-cells. In this study, we investigated the effects of age on β-cell function and autophagy in pancreatic islets of 4-month-old (young), 14-month-old (adult), and 24-month-old (old) male Wistar rats. We found that islet β-cell function decreased gradually with age. Protein expression of the autophagy markers LC3/Atg8 and Atg7 exhibited a marked decline in aged islets. The expression of Lamp-2, a good indicator of autophagic degradation rate, was significantly reduced in the islets of old rats, suggesting that autophagic degradation is decreased in the islets of aged rats. However, protein expression of beclin-1/Atg6, which plays an important role in the induction and formation of the pre-autophagosome structure by associating with a multimeric complex of autophagy regulatory proteins (Atg14, Vps34/class 3 PI3 kinase, and Vps15), was most prominent in the islets of adult rats, and was higher in 24-month-old islets than in 4-month-old islets. The levels of p62/SQSTM1 and polyubiquitin aggregates, representing the functions of autophagy and proteasomal degradation, were increased in aging islets. 8-Hydroxydeoxyguanosine, a marker of mitochondrial and nuclear DNA oxidative damage, exhibited strong immunostaining in old islets. Analysis by electron microscopy demonstrated swelling and disintegration of cristae in the mitochondria of aged islets. These results suggest that β-cell and autophagic function in islets decline simultaneously with increasing age in Wistar rats, and that impaired autophagy in the islets of older rats may cause accumulation of misfolded and aggregated proteins and reduce the removal of abnormal mitochondria in β-cells, leading to reduced β-cell function. Dysfunctional autophagy in islets during the aging process may be an important mechanism leading to the development of type 2 diabetes.

The effect of age on the changes in bone mineral density and osteoporosis detection rates in Han Chinese men over the age of 50.

Abstract Objective: To examine the relationship between age and BMD at different skeletal sites and osteoporosis (OP) detection rates in Han Chinese men over 50 years and to assess the diagnostic value of the OSTA. Methods: A retrospective analysis of 1488 men over 50 was carried out and group comparisons were made. Results: BMDs at total hip and femoral neck decreased with age (p < 0.01) and were negatively correlated with age by liner correlation analysis (r = −0.36, −0.30; p all <0.05). The detection rates of OP and osteopenia were 10.08% and 43.21% respectively, which increased with age, and significantly higher among over 70 years old than under 70 individuals (47.75% versus 35.56%; 14.88% versus 1.99%; p all <0.01). The detection rate at the femoral neck was similar to the overall detection rate. Sensitivities of OSTA index at a cutoff value of −1 and −4 were 87.33% and 52.0% respectively, and the specificities were 56.20% and 87.59%. Conclusion: BMDs at femoral neck and total hip decrease with age. Detection rates of OP increase with age. Bilateral femoral neck BMD measurement can improve detection rates of OP. OSTA is a useful screening tool for OP in Han Chinese men over 50 years.

Hepatotoxicity induced by zoledronic acid in an aged woman with primary osteoporosis.

Zoledronic acid, a bisphosphonate, has been approved for treatment and prevention of osteoporosis. This case describes a 73-year-old woman with primary osteoporosis who developed transient hepatotoxicity after zoledronic acid (ZOL) treatment. Three days after ZOL infusion, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were increased by 9.9, 8.1, and 3.7 times, respectively, compared with pretreatment values. Liver protective agents were administered. The aminotransferase returned within normal ranges 12 days post-infusion. Currently, the relationship of ZOL and liver damage is not quite clear, which cannot be explained by its pharmacokinetics. The aim of this case report is to increase the clinicians awareness of the possible adverse effect on the liver, and ZOL should be cautiously administered in patients with liver disease.

Retraction Note to: Adipose stromal-vascular fraction-derived paracrine factors regulate adipogenesis

Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to metabolic disease. Therefore, the adipogenic potential of different fat depots was investigated and found to be higher in subcutaneous compared with visceral stromal–vascular fraction (SVF), which contains adipocyte precursor cells. This increased differentiation capacity was not due to elevated numbers of Lin−Sca1+CD29+CD34+Pref1+ precursor cells, as the number of preadipocytes was higher in visceral than in subcutaneous SVF. The secreted heat-sensitive factors from the SVF inhibited adipocyte differentiation more in visceral than in subcutaneous SVF. In order to explore secreted proteins that potentially inhibit differentiation, the secretome of murine SVF was analyzed by mass spectrometry, which resulted in the identification of 113 secreted proteins with an overlap of 42 % between subcutaneous and visceral SVF. Comparison of the mRNA expression in SVF from both depots revealed 16 transcripts that were significantly expressed more in visceral than in subcutaneous SVF. A functional differentiation screen identified seven potential inhibitory candidates: biglycan, decorin, bone morphogenic protein 1, epidermal growth factor-containing fibulin-like extracellular matrix protein 2, elastin microfibril interfacer 1, matrix gla protein, and Sparc-like 1. For further verification, murine recombinant decorin or Sparc-like 1 was added to the media during the differentiation process leading to a dose-dependent decrease in adipogenesis. Further analysis will be necessary to assess the impact of the other candidates on adipocyte differentiation.

Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

The incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.

Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes Mellitus: A Pilot MRI Study

Objective The aim of this study is to investigate the cerebral cortical thickness changes in type 2 diabetes mellitus (T2DM) using a whole brain cortical thickness mapping system based on brain magnetic resonance imaging (MRI).Methods High resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MR images were obtained from 16 patients with T2DM, as well as from 16 normal controls. The whole brain cortical thickness maps were generated, and the cortical thickness of each brain region was calculated according to gyral based regions of interest (ROI) using an automated labeling system by the Freesurfer software. We compared mean cortical thickness at each brain region by the analysis of covariance with age and sex as covariates. The regional difference of the cortical thickness over the whole brain was compared by the analysis of surface-based cortical thickness.Results Mean cortical thicknesses analysis showed bilateral cerebrum in the patients with T2DM (left: 2.52±0.07 mm; right: 2.51±0.08 mm) were significant thinner than those in the normal controls (left: 2.56±0.09 mm; right: 2.56±0.09 mm) (both P<0.05). Regional cortical thinning in T2DM was demonstrated in the paracentral lobule, postcentral gyrus, lateral occipital gyrus, lingual gyrus, precuneus, superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus and posterior cingulate gyrus, compared to the normal controls. The cortical thickness of left middle cingulate and right inferior temporal gyrus were negatively correlated with the disease course.Conclusion A widespread cortical thinning was revealed in patients with T2DM by the analysis of brain cortical thickness on MR. Our finding supports the idea that T2DM could lead to subtle diabetic brain structural changes.