RESUMO
The Znt7 gene encodes a ubiquitously expressed zinc transporter that is involved in transporting cytoplasmic zinc into the Golgi apparatus and a ZnT7-containing vesicular compartment. Overexpression of ZnT7 in the pancreatic ß-cell stimulates insulin synthesis and secretion through regulation of insulin gene transcription. In this study, we demonstrate that ZnT7 is expressed in the mouse skeletal muscle. The activity of the insulin signaling pathway was down-regulated in myocytes isolated from the femoral muscle of Znt7 knock-out (KO) mice. High fat diet consumption (45% kcal) induced weight gain in male Znt7 KO mice but not female Znt7 KO mice. Male Znt7 KO mice fed the high fat diet at 5 weeks of age for 10 weeks exhibited hyperglycemia in the non-fasting state. Oral glucose tolerance tests revealed that male Znt7 KO mice fed the high fat diet had severe glucose intolerance. Insulin tolerance tests showed that male Znt7 KO mice were insulin-resistant. Diet-induced insulin resistance in male Znt7 KO mice was paralleled by a reduction in mRNA expression of Insr, Irs2, and Akt1 in the primary skeletal myotubes isolated from the KO mice. Overexpression of ZnT7 in a rat skeletal muscle cell line (L6) increased Irs2 mRNA expression, Irs2 and Akt phosphorylation, and glucose uptake. We conclude that a combination of decreased insulin secretion and increased insulin resistance accounts for the glucose intolerance observed in Znt7 KO mice.
Assuntos
Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/fisiologia , Glucose/metabolismo , Resistência à Insulina , Ração Animal , Animais , Composição Corporal , Diabetes Mellitus Experimental/metabolismo , Dieta , Feminino , Regulação da Expressão Gênica , Homeostase , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Células Musculares/citologia , Transdução de Sinais , Zinco/metabolismoRESUMO
As opioid prescribing has dramatically expanded over the past decade, so too has the problem of prescription drug abuse. In response to these now two major public health problems - the problem of poorly treated chronic pain and the problem of opioid abuse - a new paradigm has arisen in pain management, namely risk stratification. Once a prescriber has determined that opioids will be used (a medical decision based on how intense the pain is, what has been tried and failed and, to some extent, what type of pain the patient has), he/she must then decide how opioid therapy is to be delivered. Different models of delivery of opioid therapy can be utilized, beginning the process with a risk assessment that is highly individualized to each patient. Recently, researchers have produced a wide variety of literature regarding assessment tools to be used for this purpose. And while there remains a need for larger prospective studies to examine the ability of each tool to predict aberrant drug-taking behaviors, clinicians can and should utilize one or more of these screening tools and understand their benefits and limitations. This chapter will describe the nature of current screening assessments, their potential for use in the pain population in various settings, past clinical observations and suggestions for moving forward.
Assuntos
Analgésicos Opioides/uso terapêutico , Programas de Rastreamento/métodos , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor/tratamento farmacológico , Testes Psicológicos , Humanos , Medição de Risco , Estados UnidosRESUMO
Low-income women have very high rates of depression and also face a number of unique barriers that can prevent them from seeking, accepting, engaging in, or benefiting from psychotherapy treatment. Untreated depression often leads to deleterious psychological consequences for these women and their children, and may also diminish a woman's ability to improve her economic circumstances. We reviewed the literature on psychotherapeutic interventions for depressed, low-income women, identifying a number of practical, psychological, and cultural barriers that often prevent them from engaging in psychotherapy. Next, we assessed the degree to which established intervention programs help women overcome these barriers. The data suggest that it is quite difficult to engage depressed, low-income women in psychotherapy, but that a number of standard psychotherapy approaches do show promise. However, we found that many of the currently available interventions fail to fully address the barriers that prevent this population from engaging in treatment. Moreover, the impact these interventions have on engagement and attrition rates or clinical improvements is often inadequately reported. We provide preliminary recommendations for clinicians who work with low-income women as well as suggestions for bolstering the literature base.