Rimonabant as an adjunct therapy in overweight/obese patients with type 2 diabetes: reply

Thank you for forwarding the letter of the distinguished colleagues,Andre Scheen and Luc Van Gaal, and the opportunity     

We need to know more: nurse educators' interest and expertise in gerontology.

An assessment was made of 129 faculty who teach nursing students about the care of aged clients to determine their level of interest and expertise in 21 content areas related to gerontology. Faculty rated their expertise consistently lower than the relevance of, and their interest in, each of the content areas. Areas identified as most important for their professional growth tended to be areas where faculty ranked their expertise as already being high. The mean self-rated expertise of faculty who taught a course in gerontological nursing was significantly higher than those who did not. Most respondents lacked formal education in gerontology: 9% of respondents had gerontology in their undergraduate program; 27% in their graduate program. Only 4% were certified as gerontological nurses or gerontological nurse practitioners.     

Expression of six transmembrane protein of prostate 2 in human adipose tissue associates with adiposity and insulin resistance

CONTEXT: Six transmembrane protein of prostate 2 (STAMP2) is a counterregulator of adipose inflammation and insulin resistance in mice. Our hypothesis was that STAMP2 could be involved in human obesity and insulin resistance. OBJECTIVE: The objective of the study was to elucidate the role of adipose STAMP2 expression in human obesity and insulin resistance. DESIGN: The design was to quantify STAMP2 in human abdominal sc and omental white adipose tissue (WAT), isolated adipocytes, and stroma and in vitro differentiated preadipocytes and relate levels of STAMP2 in sc WAT to clinical and adipocyte phenotypes involved in insulin resistance. PARTICIPANTS: Nonobese and obese women and men (n = 236) recruited from an obesity clinic or through local advertisement. MAIN OUTCOME MEASUREMENT: Clinical measures included body mass index, body fat, total adiponectin, and homeostasis model assessment as measure of overall insulin resistance. In adipocytes we determined cell size, sensitivity of lipolysis and lipogenesis to insulin, adiponectin secretion, and inflammatory gene expression. RESULTS: STAMP2 levels in sc and visceral WAT and adipocytes were increased in obesity (P = 0.0008-0.05) but not influenced by weight loss. Increased WAT STAMP2 levels associated with a high amount of body fat (P = 0.04), high homeostasis model assessment (P = 0.01), and large adipocytes (P = 0.02). Subjects with high STAMP2 levels displayed reduced sensitivity of adipocyte lipogenesis (P = 0.04) and lipolysis (P = 0.03) to insulin but had normal adiponectin levels. WAT STAMP2 levels correlated with expression of the macrophage marker CD68 (P = 0.0006). CONCLUSION: Human WAT STAMP2 associates with obesity and insulin resistance independently of adiponectin, but the role of STAMP2 in obesity and its complications seems different from that in mice.     

<Emphasis Type="Italic">FAM13A</Emphasis> and <Emphasis Type="Italic">POM121C</Emphasis> are candidate genes for fasting insulin: functional follow-up analysis of a genome-wide association study

Aims/hypothesis

By genome-wide association meta-analysis, 17 genetic loci associated with fasting serum insulin (FSI), a marker of systemic insulin resistance, have been identified. To define potential culprit genes in these loci, in a cross-sectional study we analysed white adipose tissue (WAT) expression of 120 genes in these loci in relation to systemic and adipose tissue variables, and functionally evaluated genes demonstrating genotype-specific expression in WAT (eQTLs).

Methods

Abdominal subcutaneous adipose tissue biopsies were obtained from 114 women. Basal lipolytic activity was measured as glycerol release from adipose tissue explants. Adipocytes were isolated and insulin-stimulated incorporation of radiolabelled glucose into lipids was used to quantify adipocyte insulin sensitivity. Small interfering RNA-mediated knockout in human mesenchymal stem cells was used for functional evaluation of genes.

Results

Adipose expression of 48 of the studied candidate genes associated significantly with FSI, whereas expression of 24, 17 and 2 genes, respectively, associated with adipocyte insulin sensitivity, lipolysis and/or WAT morphology (i.e. fat cell size relative to total body fat mass). Four genetic loci contained eQTLs. In one chromosome 4 locus (rs3822072), the FSI-increasing allele associated with lower FAM13A expression and FAM13A expression associated with a beneficial metabolic profile including decreased WAT lipolysis (regression coefficient, R?=??0.50, p?=?5.6?×?10^?7). Knockdown of FAM13A increased lipolysis by ~1.5-fold and the expression of LIPE (encoding hormone-sensitive lipase, a rate-limiting enzyme in lipolysis). At the chromosome 7 locus (rs1167800), the FSI-increasing allele associated with lower POM121C expression. Consistent with an insulin-sensitising function, POM121C expression associated with systemic insulin sensitivity (R?=??0.22, p?=?2.0?×?10^?2), adipocyte insulin sensitivity (R?=?0.28, p?=?3.4?×?10^?3) and adipose hyperplasia (R?=??0.29, p?=?2.6?×?10^?2). POM121C knockdown decreased expression of all adipocyte-specific markers by 25–50%, suggesting that POM121C is necessary for adipogenesis.

Conclusions/interpretation

Gene expression and adipocyte functional studies support the notion that FAM13A and POM121C control adipocyte lipolysis and adipogenesis, respectively, and might thereby be involved in genetic control of systemic insulin sensitivity.

     

Family history of diabetes is associated with enhanced adipose lipolysis: Evidence for the implication of epigenetic factors

Aims

Type 2 diabetes is associated with insulin resistance, adipose hypertrophy and increased lipolysis. The heritability of these traits has been determined by associating them with a family history of diabetes.

Development of a measure of resident satisfaction with the nursing home

A satisfaction instrument specifically designed for use with nursing home residents, the Satisfaction with the Nursing Home Instrument (SNHI), was developed and tested with a sample of 110 nursing home residents from three proprietary facilities in Minnesota. As hypothesized, significant relationships were found between SNHI scores and measures of affect (negatively associated with depression and positively associated with morale), providing support for the construct validity of the scale. The lack of a significant relationship between SNHI scores and both age and mental status confirmed the predicted divergent validity of the instrument. The alpha coefficient for the 29-item scale was 0.81.     

The effect of fibre source and fermentation on the apparent hydrophobic binding properties of wheat bran preparations for the mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)

Preparations of dietary fibre have an ability to bind potentiallytoxic compounds in vitro, but it is unclear how the measuredbinding properties are a reflection of either the relative affinityof such compounds for fibre or the saturation binding capacityof the fibre. Cooking and processing of foods and fermentationactivity in the colon can result in significant modificationof the structure of the fibre matrix. Hence, binding propertiesmeasured in vitro may be significantly altered from those atthe proposed site of fibre activity. Using cell wall material(CWM) prepared from three distinct wheat fibre sources, theeffects of fermentation have been monitored and the consequenceson the binding properties assessed. The CWM preparations werefermented for either 0, 6, 18 or 24 h in vitro, using a humanfaecal inoculum. The coarse bran CWM was also subjected to asimulated gastric treatment. Fermentation resulted in a lossof material from each CWM preparation, the loss being consistentwith the bran source, and the maximum extent of fermentationwas reached within 18 h. The in vitro binding of the mutagen2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) to theunfermented and fermented fibre fractions showed fine bran CWMhad a much higher affinity for MeIQx than coarse bran. A 6 hfermentation had little effect on the binding affinity to finebran, but the affinity for coarse bran became similar to thatof the fine bran. Further fermentation for 18 h or 24 h resultedin a further slight increase in the binding affinity for coarseand fine bran, but, more significantly, the binding capacityof each was increased. The binding properties of the beeswingbran were not significantly affected by fermentation. Wheatbran has the potential to bind hydrophobic mutagens in the dietand this potential can be enhanced after fermentation undercolonic conditions.     

Glial-neuronal interactions are impaired in the schizophrenia model of repeated MK801 exposure.

Schizophrenia-mimicking compounds such as phencyclidine (PCP) and MK801 are antagonists at the N-methyl-D-aspartate (NMDA) receptor and produce the whole spectrum of positive, negative, and cognitive symptoms. This is one of the most important pillars of the hypoglutamatergic hypothesis of schizophrenia. Since the synthesis of glutamate and GABA in neurons is closely connected to astrocyte metabolism, the study of astrocytic function is essential in this context. Dizocilpine-maleate (MK801) (0.5 mg/kg) was injected into rats every day for 6 days. The last dose was given together with [1-(13)C]glucose and [1,2-(13)C]acetate. Extracts from frontal, retrosplenial, and cingulate cortices (CRFC) and temporal lobes were examined by (13)C nuclear magnetic resonance spectroscopy, high pressure liquid chromatography, and light microscopy. In CRFC, significant increases in the levels of glutamate, glutathione, and taurine were seen, whereas amounts and turnover of noradrenaline, dopamine, and serotonin were unchanged. Glutamate and glutamine, derived from [1,2-(13)C]acetate and thus astrocytes, were significantly decreased in CRFC as compared to controls. Labeling from [1-(13)C]glucose and thus mostly neuronal metabolism was affected in the same brain region with decreased labeling of glutamate and GABA. The present model mimics the increased glutamate/glutamine activity found in drug-naive patients with first episode schizophrenia. Moreover, the decreased labeling indicates the transition to lower glutamatergic function seen in chronic schizophrenia patients. The disturbance in astrocytic function and the glutamine-glutamate-GABA cycle are of significant importance and might add to the malfunction of the cortico-striato-thalamo-cortical loop caused by NDMA receptor blockade.