140 research outputs found
Role of insulin dysregulation in the development of yoshida sarcoma-induced cancer cachexia
No full textCancer cachexia is a devastating syndrome present in many individuals with cancer. Characterized by weight loss, loss of appetite, and wasting of skeletal muscle and adipose tissue, cachexia is associated with an increase in both morbidity and mortality in this population. The majority of individuals with cancer will experience some degree of cachexia during the course of their disease, making cachexia a clinically relevant syndrome for which the contributing mechanisms are largely unknown. A decline in insulin function, as measured by reduced glucose tolerance and insulin sensitivity, is common in individuals with and animal models of cancer cachexia. The present series of experiments was designed to examine the role of this insulin dysregulation in the development of cancer cachexia in rats bearing the Yoshida sarcoma. In experiment 1, insulin sensitivity was measured during the tumor growth period to determine when insulin dysregulation begins, relative to changes in body composition associated with cancer cachexia (Chapter 2). In Experiment 2, control and tumor-bearing animals were treated daily with saline or Exnedin-4, a GLP-1 agonist, in order to determine whether cachexia could be prevented by improving insulin sensitivity (Chapter 3). In Experiment 3, animals were fed a chow diet or a high-fat diet prior to tumor implantation, to determine if diet-induced insulin resistance modifies the development of cachexia in rats bearing the Yoshida sarcoma (Chapter 4). Our results indicate that 1) insulin dysregulation is present in Yoshida sarcoma-bearing rats prior to the onset of cachexia, 2) prevention of insulin dysregulation via chronic Exendin-4 treatment prevents the development of some cancer cachexia symptoms, and 3) the induction of insulin dysregulation via high-fat diet feeding accelerates the development of cancer cachexia. Further research is necessary to determine the mechanisms through which insulin dysregulation develops, as alterations in insulin signaling do not appear to contribute significantly to the observed effects
Endocrine effects of a low-carbohydrate, high-fat ketogenic diet
No full textLow-carbohydrate, high-fat ketogenic diets (KD) have become popular in recent years and are often used in an effort to control body weight. Our laboratory examines how maintenance on a ketogenic diet affects the multiple peripheral and central neuroendocrine systems involved in the regulation of energy balance in rats. We have previously observed increases in epididymal fat pad weight, and plasma leptin and ghrelin concentrations, as well as decreases in plasma insulin concentrations following a 7-week KD. The present series of experiments explored the development of changes in plasma endocrine hormone profiles over the course of an 8-week KD and the endocrine effects of returning to a chow diet (CH) following 8 weeks of KD consumption. Rats were maintained on CH or KD and sacrificed after 1, 4, or 8 weeks of diet maintenance (Experiment 1). We found significant increases in epididymal fat pad weight only after the full duration of KD maintenance. Plasma leptin levels were also elevated in KD rats. Contrary to previous studies, the present experiment did not observe alterations in plasma insulin or ghrelin levels. In Experiment 2, rats were maintained on CH or KD for a total of 8 weeks. Following this time, KD rats were switched to consuming CH and sacrificed after 1, 4, or 8 weeks of CH feeding (9, 12, and 16 total weeks). Results were compared to data collected after 8 weeks of maintenance on the original assigned diet. We observed increases in caloric intake and plasma insulin concentrations following the switch from KD to CH, starting at weeks 14 and 16, respectively. Epididymal fat pad weights and plasma leptin concentrations remained at levels exhibited at the end of KD maintenance following the diet switch. The present series of experiments demonstrates the ability of KD to produce alterations in plasma endocrine hormones not only during diet maintenance, but also following the switch to an alternative diet
Resilience and regime shifts: Assessing cascading effects
No full textMost accounts of thresholds between alternate regimes involve a single, dominant shift defined by one, often slowly changing variable in an ecosystem. This paper expands the focus to include similar dynamics in social and economic systems, in which multiple variables may act together in ways that produce interacting regime shifts in social-ecological systems. We use four different regions in the world, each of which contains multiple thresholds, to develop a proposed general model of threshold interactions in social-ecological systems. The model identifies patch-scale ecological thresholds, farm- or landscape-scale economic thresholds, and regional-scale sociocultural thresholds. Cascading thresholds, i.e., the tendency of the crossing of one threshold to induce the crossing of other thresholds, often lead to very resilient, although often less desirable, alternative states
Towards a deeper understanding of the social in resilience: the contributions of cultural landscapes
No full text
- …
