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It is well established that chronic glucocorticoid exposure causes hyperglycemia. While glucocorticoid receptor (GR) stimulates hepatic gluconeogenic gene transcription, additional mechanisms are activated by chronic glucocorticoid exposure to enhance gluconeogenesis. We found that chronic glucocorticoid treatment activated sphingosine-1-phosphate (S1P)-mediated signaling. Hepatic knockdown of hepatic S1P receptor 1 (S1PR1) had no effect on chronic glucocorticoid-induced glucose intolerance but elevated fasting plasma insulin levels. In contrast, hepatic S1PR3 knockdown exacerbated chronic glucocorticoid-induced glucose intolerance without affecting fasting plasma insulin levels. Finally, hepatic S1PR2 knockdown attenuated chronic glucocorticoid-induced glucose intolerance and reduced fasting plasma insulin levels. Here, we focused on dissecting the role of S1PR2 signaling in chronic glucocorticoid response on glucose homeostasis. We found that chronic glucocorticoid-induced hepatic gluconeogenesis, gluconeogenic gene expression, and GR recruitment to the glucocorticoid response elements (GREs) of gluconeogenic genes were all reduced in hepatic S1PR2 knockdown male mice. Hepatic S1PR2 knockdown also enhanced glucocorticoid suppression of RAR-related orphan receptor γ (RORγ) expression. Hepatic RORγ overexpression in hepatic S1PR2 knockdown mice restored glucocorticoid-induced glucose intolerance, gluconeogenic gene expression, and GR recruitment to their GREs. Conversely, RORγ antagonist and the reduction of hepatic RORγ expression attenuated such glucocorticoid effects. Thus, chronic glucocorticoid exposure induces an S1PR2-RORγ axis to cooperate with GR to enhance hepatic gluconeogenesis. Overall, this work provides novel mechanisms of and pharmaceutical targets against steroid-induced hyperglycemia.Article highlights

Discussed here is an analytical method for profiling lipids and phospholipids directly from mammalian tissues excised from Mus musculus (house mouse). Biochemical analysis was accomplished through the use of matrix-assisted laser desorption/ionization (MALDI) Fourier transform mass spectrometry, where whole tissue sections of mouse brain, heart, and liver were investigated. Lipid and phospholipid ions create complex MALDI mass spectra containing multiple ions with different m/z values corresponding to the same fundamental chemical species. When a computational sorting approach is used to group these ions, the standard deviation for observed relative chemical abundance can be reduced to 6.02%. Relative standard deviations of 10% are commonly accepted for standard chromatographic phospholipid analyses. Average mass measurement accuracy for 232 spectra representing three tissue types from 12 specimens was calculated to be 0.0053 Da. Further it is observed, that the data and the analysis between all the animals have near-identical phospholipid contents in their brain, heart, and liver tissues, respectively. In addition to the need to accurately measure relative abundances of phospholipid species, it is essential to have adequate mass resolution for complete and accurate overall analysis. It is reasonable to make mass composition assignments with spectral resolving power greater than 8000. However, results from the present study reveal 14 instances ([C.sup.12] carbon isotope) of multiple m/z ions having the same nominal value that require greater resolution in order that overlap will not occur. Spectra measured here have an average resolving power of 12 000. It is established that high mass resolution and mass accuracy coupled with MALDI ionization provide for rapid and accurate phospholipid analysis of mammalian tissue sections.

We recently compared the regulation of glucose-6-phosphatase (G-6-Pase) catalytic subunit and glucose 6-phosphate (G-6-P) transporter gene expression by insulin in conscious dogs in vivo (Hornbuckle LA, Edgerton DS, Ayala JE, Svitek CA, Neal DW, Cardin S, Cherrington AD, and O'Brien RM. Am J Physiol Endocrinol Metab 281: E713-E725, 2001). In pancreatic-clamped, euglycemic conscious dogs, a 5-h period of hypoinsulinemia led to a marked increase in hepatic G-6-Pase catalytic subunit mRNA; however, G-6-P transporter mRNA was unchanged. Here, we demonstrate, again using pancreatic-clamped, conscious dogs, that glucagon is a candidate for the factor responsible for this selective induction. Thus glucagon stimulated G-6-Pase catalytic subunit but not G-6-P transporter gene expression in vivo. Furthermore, cAMP stimulated endogenous G-6-Pase catalytic subunit gene expression in HepG2 cells but had no effect on G-6-P transporter gene expression. The cAMP response element (CRE) that mediates this induction was identified through transient transfection of HepG2 cells with G-6-Pase catalytic subunit-chloramphenicol acetyltransferase fusion genes. Gel retardation assays demonstrate that this CRE hinds several transcription factors including CRE-binding protein and CCAAT enhancer-binding protein. insulin; fatty acids; gene transcription; cyclic adenosine monophosphate; glucose-6-phosphatase; glucose 6-phosphate

Organizational Behavior Management (OBM) has improved staff performance in mental hospitals and homes for the mentally retarded. In the present study, OBM techniques of goal-setting, feedback, and positive reinforcement were used to improve staff behavior and patient outcomes in four private adult group homes for chronic mental patients. Four therapists and 37 patients served as subjects. After a 10 or 20 week multiple baseline, the therapist received training in setting measurable goals, providing verbal and graphic feedback, and praising patients. In addition, therapists received written and verbal feedback, praise and contingent monetary reinforcement. Results revealed large increases in the number of goals addressed weekly and in the quality of treatment plan reviews during treatment. There was a significant increase in patient goal progress and patient activity level, and a significant decrease in therapists' time to submit applicable paperwork, during treatment. These results suggest that OBM techniques can improve therapist performance and patient outcomes in group homes for chronic metal patients. Keywords: Behavior systems analysis, OBM, behavior therapists-patient interactions, goals, feedback, social and monetary reinforcement, Medicare and Medicaid compliance and reimbursements, mental health organization

I. INTRODUCTION Insulin regulates metabolism by altering the synthesis, stability, or translation of specific mRNAs or by producing activity-altering modifications of preexisting enzyme molecules. The latter represents a well-recognized action [...]

A study was conducted on quality control. Formal competition was employed as an intervention to improve quality control in a package delivery company. A baseball analog system was used to implement a competitive program of feedback and positive reinforcement. The program indicated improvements in quality. The results suggest that internal competition can be an effective intervention to improve quality control.

The probability of burnout among employees involved in developmental disability care and services was investigated using the Maslach Burnout Inventory criterion. A group of employees working in five facilities that serve adults with primary diagnosis of mental retardation was used in the study. Results show that about two-thirds of the employees experienced burnout or became uninvolved with their patients after a considerable period of time.

Recent work with operant procedures in sports has shown that feedback, reinforcement, and chaining can be effective techniques in improving performance. In many cases, however, a problem remains in getting the participants to practice the appropriate responses. In the present study, 14 college golfers were put on successive contingency contracts over three weeks to go through the Total Golf chaining-mastery program of Simek and O'Brien. Rewards consisted of activities such as spots on the starting team and the opportunity to play better courses as well as tangible rewards such as new golf balls. After the first two weeks of training, through 19 steps backward from the green, the mean of three posttraining rounds for these 14 golfers was 3.4 strokes lower than the mean of their three rounds at baseline. At this point, the coach did not follow through with the rewards promised in the second contract. Having been placed on extinction, only three of the 14 players followed through on the third contract. In this return to baseline-like condition an average increase of over two strokes for the team as a whole was noted. The number of steps of the chain mastered in practice and the difference between mean scores at baseline and the last measurement period correlated .86, indicating that 74% of the improvement in golf scores was accounted for by performance on the mastery chain.