Stakeholder Perspectives on Implementing a Police-Mental Health Collaborative to Improve Pathways to Treatment.

High rates of criminal justice involvement among individuals with mental illness have led to collaborative efforts between law enforcement agencies and mental health providers to improve crisis responses and pathways to treatment. The development and implementation of these police-mental health collaborations (PMHCs) have received little attention in the literature, but these processes are crucial in understanding feasibility and sustainability. The PMHC discussed here is an interagency effort to identify individuals involved with law enforcement who have unmet behavioral health needs and engage them in services.

CDK4 is an essential insulin effector in adipocytes.

Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology.

Oral insulin-mimetic compounds that act independently of insulin.

The hallmarks of insulin action are the stimulation and suppression of anabolic and catabolic responses, respectively. These responses are orchestrated by the insulin pathway and are initiated by the binding of insulin to the insulin receptor, which leads to activation of the receptor's intrinsic tyrosine kinase. Severe defects in the insulin pathway, such as in types A and B and advanced type 1 and 2 diabetes lead to severe insulin resistance, resulting in a partial or complete absence of response to exogenous insulin and other known classes of antidiabetes therapies.

Peroxisome proliferator-activated receptor gamma regulates E-cadherin expression and inhibits growth and invasion of prostate cancer.

Peroxisome proliferator-activated receptor gamma (PPARgamma) might not be permissive to ligand activation in prostate cancer cells. Association of PPARgamma with repressing factors or posttranslational modifications in PPARgamma protein could explain the lack of effect of PPARgamma ligands in a recent randomized clinical trial. Using cells and prostate cancer xenograft mouse models, we demonstrate in this study that a combination treatment using the PPARgamma agonist pioglitazone and the histone deacetylase inhibitor valproic acid is more efficient at inhibiting prostate tumor growth than each individual therapy.

Cyclin D3 promotes adipogenesis through activation of peroxisome proliferator-activated receptor gamma.

In addition to their role in cell cycle progression, new data reveal an emerging role of D-type cyclins in transcriptional regulation and cellular differentiation processes. Using 3T3-L1 cell lines to study adipogenesis, we observed an up-regulation of cyclin D3 expression throughout the differentiation process. Surprisingly, cyclin D3 was only minimally expressed during the initial stages of adipogenesis, when mitotic division is prevalent.

Cdk4 promotes adipogenesis through PPARgamma activation.

Cell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis.

Exploring the binding mode of semicarbazide-sensitive amine oxidase/VAP-1: identification of novel substrates with insulin-like activity.

We previously reported that substrates of semicarbazide-sensitive amine oxidase in combination with low concentrations of vanadate exert potent insulin-like effects. Here we performed homology modeling of the catalytic domain of mouse SSAO/VAP-1 and searched through chemical databases to identify novel SSAO substrates. The modeling of the catalytic domain revealed that aromatic residues Tyr384, Phe389, and Tyr394 define a pocket of stable size that may participate in the binding of apolar substrates.

Semicarbazide-sensitive amine oxidase activity exerts insulin-like effects on glucose metabolism and insulin-signaling pathways in adipose cells.

Semicarbazide-sensitive amine oxidase (SSAO) is very abundant at the plasma membrane in adipocytes. The combination of SSAO substrates and low concentrations of vanadate markedly stimulates glucose transport and GLUT4 glucose transporter recruitment to the cell surface in rat adipocytes by a mechanism that requires SSAO activity and hydrogen peroxide formation. Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase.

Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 activity exerts an antidiabetic action in Goto-Kakizaki rats.

In this study we have explored whether the bifunctional protein semicarbazide-sensitive amine oxidase (SSAO)/vascular adhesion protein-1 (VAP-1) represents a novel target for type 2 diabetes. To this end, Goto-Kakizaki (GK) diabetic rats were treated with the SSAO substrate benzylamine and with low ineffective doses of vanadate previously shown to have antidiabetic effects in streptozotocin-induced diabetic rats. The administration of benzylamine in combination with vanadate in type 2 diabetic rats acutely stimulated glucose tolerance, and the chronic treatment normalized hyperglycemia, stimulated glucose transport in adipocytes, and reversed muscle insulin resistance.