Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
 ...
PMID:Anatomy and regulation of the central melanocortin system. 1585 65

Chronic sleep loss as a consequence of voluntary bedtime restriction is an endemic condition in modern society. Although sleep exerts marked modulatory effects on glucose metabolism, and molecular mechanisms for the interaction between sleeping and feeding have been documented, the potential impact of recurrent sleep curtailment on the risk for diabetes and obesity has only recently been investigated. In laboratory studies of healthy young adults submitted to recurrent partial sleep restriction, marked alterations in glucose metabolism including decreased glucose tolerance and insulin sensitivity have been demonstrated. The neuroendocrine regulation of appetite was also affected as the levels of the anorexigenic hormone leptin were decreased, whereas the levels of the orexigenic factor ghrelin were increased. Importantly, these neuroendocrine abnormalities were correlated with increased hunger and appetite, which may lead to overeating and weight gain. Consistent with these laboratory findings, a growing body of epidemiological evidence supports an association between short sleep duration and the risk for obesity and diabetes. Chronic sleep loss may also be the consequence of pathological conditions such as sleep-disordered breathing. In this increasingly prevalent syndrome, a feedforward cascade of negative events generated by sleep loss, sleep fragmentation, and hypoxia are likely to exacerbate the severity of metabolic disturbances. In conclusion, chronic sleep loss, behavioral or sleep disorder related, may represent a novel risk factor for weight gain, insulin resistance, and Type 2 diabetes.
 ...
PMID:Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. 1622 62

Sleep deprivation has multiple effects on endocrine and metabolic function. In particular, sleep restriction is accompanied by increased cortisol levels in the afternoon and early evening and a shorter quiescent period compared with extended sleep periods. Those alterations could facilitate central and peripheral disturbances that are associated with glucocorticoid excess, such as memory deficits, and are similar to those observed in aging. Thus, chronic sleep loss could contribute to acceleration of the aging process. Sleep restriction is also associated with an impairment of carbohydrate tolerance, similar to that observed in individuals with clinically significant impaired glucose tolerance. Thus, chronic sleep deprivation may increase the risk for diabetes. Finally, sleep plays an important role in energy balance. Partial sleep deprivation was found to be associated with a decrease in plasma levels of leptin and a concomitant increase in plasma levels of ghrelin; subjective ratings of hunger and appetite also increased (the appetite for protein-rich foods was not significantly affected). Moreover, a remarkable correlation was found between the increase in hunger and the increase in the ghrelin:leptin ratio. Thus, the neuroendocrine regulation of appetite and food intake appears to be influenced by sleep duration, and sleep restriction may favor the development of obesity.
 ...
PMID:Metabolic and endocrine effects of sleep deprivation. 1645 57

The etiology of obesity is multifactorial and still unclear. Genetic factors play a significant role and include several gene candidates: polymorphisms of genes for ss(2)-adrenoreceptor, resistin, estrogen receptor-a and peroxisome proliferator-activated receptor-gamma. Moreover, peptides regulating hunger and satiety, e.g. leptin, galanin, cholecystokinin and neuropeptide Y, and altered nutritional patterns have been implicated. Also, factors associated with aging, e.g. decreased levels of growth hormone and dehydroepiandrosterone, and the activity of the sympathetic nervous system (resting metabolism and thermogenesis) cannot be disregarded. Participation of the sex steroids and inflammatory factors has also been postulated in the etiology of obesity. Three phenotypes of obesity are postulated; however, the visceral (abdominal) phenotype is typical of postmenopausal women and is characterized by several metabolic disorders with high risks of diabetes mellitus type 2 and cardiovascular disease. On the basis of personal experience and data from evidence-based medicine, diagnostic-therapeutic algorithms of climacteric obesity are presented.
 ...
PMID:Climacteric obesity: from genesis to clinic. 1652 29

The hormone ghrelin is secreted mainly from the gut, rises in peripheral plasma before meals, and is implicated in stimulating hunger, initiating meals, and developing obesity. We hypothesize that activation of the sympathetic nervous system contributes to preprandial ghrelin surges. The present studies in isoflurane-anesthetized Wistar rats were designed to determine whether sympathetic nerves and neurohormones are capable of stimulating ghrelin secretion. We activated gut sympathetic nerves by two methods: electrical sympathetic nerve stimulation (SNS) and chemical sympathetic nerve activation with iv tyramine (TYR) administration. Portal venous blood was sampled before and during a 10-min sympathetic stimulation. Successful activation of gut sympathetic nerves was verified by increments in portal venous norepinephrine. SNS increased portal ghrelin by 206 +/- 50%. In contrast, simply isolating gut sympathetic nerves without applying current had a minimal effect on ghrelin levels. TYR also increased portal ghrelin [change (Delta), +52 +/- 11%], whereas saline infusion had little effect. We next determined whether the neural stimulation of ghrelin secretion was mediated indirectly via the suppression of insulin secretion during SNS and TYR. Streptozotocin-induced diabetes prevented a fall in insulin during TYR, yet the portal ghrelin response (Delta = +47 +/- 18%) was similar to that in nondiabetic rats. Lastly, to test for humoral stimulation of ghrelin, we infused the sympathetic neurohormone, epinephrine, to achieve levels found during severe stress. Epinephrine failed to stimulate ghrelin secretion (Delta = +4 +/- 35%). We conclude that the neural, but not the neurohumoral, branch of the sympathetic nervous system can directly stimulate ghrelin secretion.
 ...
PMID:Direct stimulation of ghrelin secretion by sympathetic nerves. 1652 47

We evaluated the prevalence of disordered eating behavior in 168 unselected outpatients with type 2 diabetes mellitus (T2DM) and the effects on the health related quality of life (HRQL). Subjects in generally good glycemic control, treated by diet or oral hypoglycemic agents (58% M; 63.8+/-SD 10.1 years; BMI, 29.7+/-5.9 kg/m2) completed self-administered questionnaires for HRQL (SF-36) and eating behavior [(Three-Factor Eating Questionnaire (TFEQ); Binge Eating Scale (BES)]. Data on HRQL were computed as effectsizes in comparison to population norm. The prevalence of altered TFEQ scales was not different between genders, and varied between 22.1% (disinhibition) and 41.4% (restriction), but only 6.7% had a positive BES score. Age (OR, 0.58 for decade; 95% CI, 0.39-0.87), duration of diabetes (OR, 1.33 for 5 years; 1.01-1.74) and BMI (OR, 1.11; 1.04-1.18) were predictive for the presence of disinhibition. BMI also predicted hunger (OR, 1.16; 1.08-1.25). SF36 domains were not different in relation to positive BES. Disinhibition at TFEQ was significantly associated with poor social functioning (p=0.018) and role-emotional (p=0.022), whereas hunger was associated with poor physical functioning (p=0.010), role-physical (p=0.0014), social functioning (p=0.015) and role-emotional (p=0.0001). Metabolic control, duration of diabetes, and the presence of complications were not associated with HRQL. A disordered eating behavior may be present in T2DM patients, and is associated with poor HRQL. This condition must be considered for an olistic approach to weight control.
 ...
PMID:Eating behavior affects quality of life in type 2 diabetes mellitus. 1675 69

To assess the satiety-promoting effect of a novel viscous fiber-containing nutrition bar, overweight and obese adult subjects with type 2 diabetes (n=99) were randomized into a double blind, crossover study. They were fed a 300kcal lunch consisting of viscous fiber-containing nutrition bars (VF) or commercial nutrition control bars designed for people with diabetes (CH). VF resulted in a 27.1% increase in fullness (p<0.05), a 15.8% decrease in prospective consumption (p<0.001), and a 14.2% decrease in hunger (p<0.001) in the 120-240min post-lunch areas under the curve (AUC) compared to CH, but no differences were observed for nausea or thirst (p>0.05). Similar results were noted for 0-300min AUC values. VF were associated with greater frequencies and intensities of abdominal distention (p<0.001) and flatulence (p<0.001), and greater frequency of stools (p<0.001) compared to CH, but there were no differences in mean or maximum (loosest) stool consistency (p>0.05). Overall, these results suggest that VF could be a useful tool in weight management of type 2 diabetes.
Diabetes Res Clin Pract 2007 Jun
PMID:Effect of a viscous fiber-containing nutrition bar on satiety of patients with type 2 diabetes. 1702 88

Ghrelin is a potent orexigenic and adipogenic hormone that strongly influences fat deposition and the generation of hunger in obesity. Indeed, hyperghrelinemia appears to promote an increase in food intake as seen in Prader-Willi Syndrome (PWS). Exendin (Ex)-4 is an agonist of the glucagon-like peptide (GLP)-1 receptor (GLP-1r) that has anorexigenic and fat-reducing properties. Here, we report that Ex-4 reduces the levels of ghrelin by up to 74% in fasted rats. These effects are dose dependent and long lasting (up to 8 h), and they can be detected after both central and peripheral administration of Ex-4. Suppression of ghrelin was neither mimicked by GLP-1(7-36)-NH(2) nor blocked by the GLP-1r antagonist Ex-(9-39). Moreover, it was independent of the levels of leptin and insulin. The decrease in ghrelin levels induced by Ex-4 may explain the reduced food intake in fasted rats, justifying the more potent anorexigenic effects of Ex-4 when compared with GLP-1. As well as the potential benefits of Ex-4 in type 2 diabetes, the potent effects of Ex-4 on ghrelin make it tempting to speculate that Ex-4 could offer a therapeutic option for PWS and other syndromes characterized by substantial amounts of circulating ghrelin.
Diabetes 2007 Jan
PMID:Exendin-4 potently decreases ghrelin levels in fasting rats. 1719 76

In normal individuals hypoglycemic counterregulation is a multifactorial, redundant process that involves reduction of insulin secretion, increasing glucagon secretion, adrenergic activation, and increased growth hormone and cortisol secretion. Metabolically, these lead to increased glucose production, initially through glycogenolysis and later through gluconeogenesis, decreased muscle glucose oxidation and storage and increased release and use of alternative fuels, primarily free fatty acids. They also lead to hypoglycemic symptoms and hunger which increase food intake. These systems are designed to provide as much glucose as possible for brain glucose use. In patients with type 1 diabetes there are multiple impairments of these responses. Insulin does not decrease. Glucagon secretion is decreased or absent. Recovery from hypoglycemia is therefore dependent on the adrenergic response. Hypoglycemia increases plasma levels of both epinephrine and norepinephrine. These catechols are released primarily from the adrenal medulla. However, it is well documented that hypoglycemic increases muscle sympathetic nerve activity, and that both alpha and beta adrenergic activity increase. Increased beta-activity increases free fatty acid release which increase glucose production and decrease glucose utilization. The increased alpha-adrenergic activity's primary role is to counteract beta-adrenergic vasodilation. It may also reduce neurogenic and neuroglycopenic symptoms. Lastly, there is evidence that both cardiac and adrenergic sensitivity are altered in type 1 diabetes. It is hoped that this information can be used in the future to help develop ways to protect patients with type 1 diabetes from hypoglycemia and its adverse effects.
Curr Diabetes Rev 2007 Aug
PMID:Sympathetic mechanisms of hypoglycemic counterregulation. 1822 Jun 70

One of the most common symptoms of diabetes is extreme hunger, but the brain mechanism underlying this hyperphagia is unknown. The endocannabinoid system has emerged as one of the main food intake regulators in the brain. However, the effects of type 1 diabetes on the endocannabinoid system are not completely known. Thus, the aim of the present work is to establish the possible alterations induced by type 1 diabetes on the brain endocannabinoid system in rats. Western blot and immunocytochemistry were used to measure CB1 and phosphorylated CB1 receptor expression in several prosencephalic regions in streptozotocin-induced type 1 diabetic rats. Serum leptin levels were measured by ELISA. CB1 receptor expression was increased in striatum and hypothalamus of diabetic animals, with no changes in other brain areas studied. CB1 receptor phosphorylation was also increased in the same brain areas. Type 1 diabetes induced significant weight loss, and serum leptin levels were severely decreased. These results reinforce the possible role of the CB1 receptor as a pharmacological target for the clinical management of appetite in diabetic patients.
 ...
PMID:Type 1 diabetes alters brain cannabinoid receptor expression and phosphorylation status in rats. 1840 37


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>