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Objective: Ectopic fat accumulation in the pancreas in response to obesity and its implication on the onset of type 2 diabetes remain poorly understood. Intermittent fasting (IF) is known to improve glucose homeostasis and insulin resistance. However, the effects of IF on fat in the pancreas and beta-cell function remain largely unknown. Our aim was to evaluate the impact of IF on pancreatic fat accumulation and its effects on islet function. Methods: New Zealand Obese (NZO) mice were fed a high-fat diet ad libitum (NZO-AL) or fasted every other day (intermittent fasting, NZO-IF) and pancreatic fat accumulation, glucose homoeostasis, insulin sensitivity, and islet function were determined and compared to ad libitum-fed B6.V-Lep(ob/ob) (ob/ob) mice. To investigate the crosstalk of pancreatic adipocytes and islets, co-culture experiments were performed. Results: NZO-IF mice displayed better glucose homeostasis and lower fat accumulation in both the pancreas (-32%) and the liver (-35%) than NZO-AL mice. Ob/ob animals were insulin-resistant and had low fat in the pancreas but high fat in the liver. NZO-AL mice showed increased fat accumulation in both organs and exhibited an impaired islet function. Co-culture experiments demonstrated that pancreatic adipocytes induced a hypersecretion of insulin and released higher levels of free fatty adds than adipocytes of inguinal white adipose tissue. Conclusions: These results suggest that pancreatic fat participates in diabetes development, but can be prevented by IF. (C) 2019 Published by Elsevier Inc.
Pancreatic steatosis associates with beta-cell failure and may participate in the development of type-2-diabetes. Our previous studies have shown that diabetes-susceptible mice accumulate more adipocytes in the pancreas than diabetes-resistant mice. In addition, we have demonstrated that the co-culture of pancreatic islets and adipocytes affect insulin secretion. The aim of this current study was to elucidate if and to what extent pancreas-resident mesenchymal stromal cells (MSCs) with adipogenic progenitor potential differ from the corresponding stromal-type cells of the inguinal white adipose tissue (iWAT). miRNA (miRNome) and mRNA expression (transcriptome) analyses of MSCs isolated by flow cytometry of both tissues revealed 121 differentially expressed miRNAs and 1227 differentially expressed genes (DEGs). Target prediction analysis estimated 510 DEGs to be regulated by 58 differentially expressed miRNAs. Pathway analyses of DEGs and miRNA target genes showed unique transcriptional and miRNA signatures in pancreas (pMSCs) and iWAT MSCs (iwatMSCs), for instance fibrogenic and adipogenic differentiation, respectively. Accordingly, iwatMSCs revealed a higher adipogenic lineage commitment, whereas pMSCs showed an elevated fibrogenesis. As a low degree of adipogenesis was also observed in pMSCs of diabetes-susceptible mice, we conclude that the development of pancreatic steatosis has to be induced by other factors not related to cell-autonomous transcriptomic changes and miRNA-based signals.
In 2011, about 1.1-1.4 million patients with dementia were living in Germany, a number expected to rise to three million by 2050. Dementia poses a major challenge to the healthcare system and neuropharmacological service provision. The aim of this study was to determine prescription rates for anti-dementia drugs as well as for neuroleptics, sedative-hypnotics and antidepressants in dementia using the complete nationwide outpatient claims data pertaining to the services of statutory health insurance. We controlled for gender, age, dementia diagnosis, physician specialty (general practitioner GP versus neuropsychiatry specialist physician NPSP), and rural and urban living area. In about one million prevalent dementia patients (N=1,014,710) in 2011, the prescription prevalence rate of anti-dementia drugs was 24.6%; it varied with gender, age, and diagnosis (highest in Alzheimer's disease; 42%), and was higher in patients treated by NPSPs (48% vs. 25% in GPs). At the same time, we found an alarmingly high rate of treatment with neuroleptics in dementia patients (35%), with an only slightly decreased risk in patients treated exclusively by NPSPs (OR=0.86). We found marginal differences between rural and urban areas. Our results show that the majority of anti-dementia drug prescriptions appear guideline-oriented, yet prescription rates are overall comparatively low. On the other hand, neuroleptic drugs, which are associated with excess morbidity and mortality in dementia, were prescribed very frequently, suggesting excess use given current guidelines. We therefore suggest that guideline implementation measures and increasing quality control procedures are needed with respect to the pharmacotherapy of this vulnerable population. (C) 2015 Elsevier B.V. and ECNR All rights reserved.