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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of enteroviruses in certain specific disease--cardiac disease, nephritis, diabetes, and hemorrhagic conjunctivitis--is examined. It has now been well documented that Coxsackievirus B (types CB1 through CB5 but not CB6) is the main pathogen involved in various clinical forms of viral heart disease. Coxsackievirus A (CA4 and CA16) and echovirus (types 9 and 22) may also be associated with viral heart disease. In regard to the etiologic role of enteroviruses in nephritis, pancreatitis, and diabetes, again CBV, especially CB3 and CB4, has been suspected, but the data are controversial and further studies are needed. Hemorrhagic conjunctivitis, a newly observed clinical entity, is caused by enterovirus 70. It has spread to four continents (not including the Americas) in a pandemic fashion since 1969 and is now one of the common eye infections in these areas. The virus has some neurovirulence, and motor paralysis is known to occur as a complication; hence it should be carefully watched in the future.
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PMID:Enteroviruses other than poliovirus. 19 2

Twenty-four consecutive children with newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) were investigated for a history of infectious disease. Thirteen of the 24 (54%) patients reported symptoms of acute infection within two months before diabetes was diagnosed. The mean age was 8.5 years and 15 (63%) of the patients were girls. No clear seasonal variation in onset was seen. Coxsackie B (CB)-virus-specific IgM responses were detected by reverse radioimmunoassay (RIA) in 16 of the 24 (67%) patients on the day of diagnosis of IDDM. The highest titre was usually recorded at that time, but with some the highest titre was found with a second serum obtained three to seven weeks after diagnosis. Thereafter the titres declined, and after six months IgM was detected only in a few patients. Thirteen patients displayed monotypic IgM responses, whereas three patients showed ditypic responses. Among the former, IgM was recorded against Coxsackie B4 (CB4) in four, B5 (CB5) in three, B1 (CB1) in two, B2 (CB2) in two, and B3 (CB3) in two patients. The ditypic responses were against CB2 and CB3, CB3 and CB4, and CB5. No CB-virus-specific IgM was detected in sera, found during the same period, from age-matched nondiabetic children without evidence of infection. In neutralisation (NT) tests, antibodies to the homotypic virus were found in 12 of the 16 diabetic patients showing CB-virus-specific at the time of diagnosis. A significant rise in NT titre was demonstrated in three of these patients. No significant clinical difference was noted between IgM positive and IgM negative patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High frequency of Coxsackie-B-virus-specific IgM in children developing type I diabetes during a period of high diabetes morbidity. 299 22

Acylethanolamides are endogenous compounds with lipid structure including anandamide (AEA), palmitoilethanolamide, oleylamide and oleylethanolamide (OEA). AEA binds to the cannabinoid receptor CB1, located at the central nervous system, while OEA is an endogenous ligand for the alpha subtype of peroxisome-proliferator activating receptor (PPARalpha). Since AEA acts on the same receptor which binds marihuana active derivatives, this group of compounds were called endocannabinoids. Besides typical central effects of cannabinoids, CB1 receptor activation leads to hyperphagia, whereas its pharmacological blockade is followed by changes in energy metabolism favouring substrate oxidation. OEA has inhibitory effects on food intake by acting on PPARalpha receptors which modulate the autonomous nervous system. Both acylethanolamides, AEA and OEA, have opposite effects suggesting that they form part of a satiety sensor system. Whereas fasting triggers AEA release and inhibits OEA synthesis, eating has the reverse effect. Additionally OEA is also produced by adipocytes ad has some effects on lipid metabolism. All these data suggest a role for acylethanolamides and the endocannabinoid system in the pathophysiology of obesity, diabetes and atherosclerosis.
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PMID:[The endocannabinoid system and food intake control]. 1538 9

The antinociceptive action of cannabinoids in acute and inflammatory pain states have been well-documented. There is also accumulating evidence suggesting that cannabinoids are effective analgesics in chronic pain conditions. WIN 55,212-2, a mixed CB1 and CB2 cannabinoid receptor agonist, has been shown to be effective against hyperalgesia and allodynia in painful peripheral mononeuropathy. Recently, in addition to their spinal and supraspinal antinociceptive action, cannabinoids have also reported to exert local analgesic effects. The aim of this study is to observe the effect of a high affinity cannabinoid, WIN 55,212-2, on tactile allodynia and thermal hyperalgesia in diabetic rats. Diabetes was produced with the injection of a single dose of streptozocin (50 mg/kg, i.p.) and this procedure resulted in neuropathic pain behaviors in the hindlimbs. Mechanical allodynia was detected by application of von Frey filaments to the plantar surface of the foot, and thermal hyperalgesia was studied using the Hargreaves' method; however, thermal hyperalgesia did not develop in diabetic rats. With its higher doses, both systemic (3 and 10 mg/kg, i.p.) and peripheral (30 microg, i.p.l.) injections of WIN 55,212-2 reduced mechanical allodynia. These results suggest that WIN 55,212-2 has an antiallodynic effect in streptozocin-induced diabetic rats and may be a promising approach in the treatment of diabetic neuropathy.
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PMID:The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. 1551 50

We investigated the effects of chronic treatment with the CB1 receptor antagonist rimonabant (10 mg/kg/day p.o. for 10 weeks) in mice with established obesity (5-month high-fat diet). Untreated obese mice showed a weight gain of 46% (45.0 +/- 0.6 g vs. 30.8 +/- 0.5 g) compared with age-matched animals fed a standard diet. Rimonabant treatment, commencing after 5-month high-fat diet, produced a marked and sustained decrease in body weight (34.5 +/- 0.8 g vs. 47.2 +/- 0.5 g in the high-fat vehicle group, p < 0.001). The anti-obesity effect of rimonabant was similar to that obtained by switching obese mice from high-fat diet to standard laboratory diet during 10 weeks (final weight 33.7 +/- 0.6 g) and was associated with only transient (14 days) reduction in energy intake. Serum leptin, insulin and glucose levels were markedly elevated in obese animals. Rimonabant treatment significantly reduced these elevations (leptin -81%, insulin -78%, glucose -67%, p < 0.001 in all cases vs. high-fat vehicle group). In addition, rimonabant treatment modestly but significantly increased serum adiponectin levels (+18%, p < 0.05 vs. high-fat vehicle group). Obese mice demonstrated abnormal serum lipid profiles. Although rimonabant did not modify high-density lipoprotein cholesterol (HDLc) and had modest effects on total cholesterol, it significantly reduced triglycerides and low-density lipoprotein cholesterol (LDLc) and, notably, increased the HDLc/LDLc ratio (12.4 +/- 0.8 vs. 7.9 +/- 0.2 in high-fat vehicle group, p < 0.001). Therefore, in a model of established obesity, chronic rimonabant treatment produces a marked and sustained decrease in body weight (equivalent to that achieved by dietary change) which is associated with favourable modifications in serum biochemical and lipid profiles.
Diabetes Obes Metab 2005 Jan
PMID:The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. 1564 77

Recent reports have described the presence of cannabinoid CB1 receptors in pancreatic islets. Here we show that administration of the endogenous cannabinoid anandamide or the selective cannabinoid CB1 receptor agonist Arachidonyl-2'-chloroethylamide (ACEA) results in glucose intolerance after a glucose load. This effect is reversed by the selective cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251). These results suggest that targeting cannabinoid CB1 receptors may serve as new therapeutic alternatives for metabolic disorders such as diabetes.
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PMID:Activation of cannabinoid CB1 receptors induces glucose intolerance in rats. 1642 47

The prevalence of Type 2 diabetes is showing a rapid progression worldwide, a phenomenon largely resulting from the epidemic proportions reached by obesity in various populations of the world. However, physicians have been puzzled by the heterogeneity of obesity as not every obese patient is characterized by chronic complications. In this regard, body fat distribution, especially intra-abdominal adipose tissue accumulation, has been found to be a key correlate of a cluster of diabetogenic, atherogenic, prothrombotic and inflammatory metabolic abnormalities increasing the risk of Type 2 diabetes and cardiovascular disease. In this regard, it has been recently demonstrated that abdominal obesity was independently associated with an increased risk of coronary heart disease and Type 2 diabetes independently of overall adiposity. Lifestyle modification programs have shown the benefits on cardiometabolic risk variables of a moderate weight loss as it has been found to be associated with a substantial loss of intra-abdominal fat in viscerally obese patients. However, to be successful, such programs require the support of a multidisciplinary team not available to most clinicians. In this context, it is proposed that pharmacotherapy of obesity should target abdominally obese patients at high risk of Type 2 diabetes and cardiovascular disease, such risk being encompassed by the notion of "cardiometabolic risk". The recent discovery of the endocannabinoid-cannabinoid receptor type 1 (CB1 receptor) system and of its impact on the regulation of energy metabolism represents a significant advance which could help physicians to target abdominal obesity and its related metabolic complications. In this regard, studies have shown that rimonabant (the first CB1 blocker developed) therapy could be useful for the management of clustering cardiovascular disease risk factors in high-risk abdominally obese patients through its marked effects on both abdominal adiposity and related metabolic risk factors.
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PMID:Intra-abdominal obesity: an untreated risk factor for Type 2 diabetes and cardiovascular disease. 1675 11

Rimonabant is the first drug to target the endocannabinoid (CB) pathway by inhibiting the actions of anandamide and 2-archidonyl-glycerol on CB1 receptors. This review gives an overview of rimonabant and the CB system and how this system relates to obesity. Rimonabant blocks the central effects of this neurotransmitter pathway involved in obesity and weight control and also blocks the direct effects of CBs on adipocyte and hepatocyte metabolism. Blockade of CB1 receptors leads to a decrease in appetite and also has direct actions in adipose tissue and the liver to improve glucose, fat and cholesterol metabolism so improving insulin resistance, triglycerides and high-density lipoprotein cholesterol (HDL-C) and in some patients, blood pressure. The Rimonabant in Obesity (RIO) trials have shown that rimonabant induces weight loss > 5% in 30-40% of patients and > 10% in 10-20% above both a dietary run-in and long-term hypocaloric management over a 2 year period with a low level of drug-related side effects. Rimonabant therapy is associated with an extra 8-10% increase in HDL-C and a 10-30% reduction in triglycerides and improvements in insulin resistance, glycaemic control in patients with diabetes and also adipokines and cytokines including C-reactive protein over hypocaloric diet therapy. In addition rimonabant abolishes the weight gain associated with smoking cessation and improves the chances of quitting smoking. Thus rimonabant has major effects on both the metabolic syndrome and cardiovascular risk factors thus has the potential to reduce the risks of type 2 diabetes and cardiovascular disease associated with the cardiometabolic phenotype.
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PMID:Rimonabant: endocannabinoid inhibition for the metabolic syndrome. 1710 77

The discovery of the endocannabinoid system (ECS) has raised a large interest in the scientific community providing us with a strikingly long list of apparently independent multi organ effects. As a result, in most reviews on this issue the main function of the ECS is considered as modulatory. Unfortunately, this vision does not add much to our understanding of the specific biological function of the ECS. Thus, modulatory is what in general all biological systems are or should be. In this review we will show that the apparent inconsistent puzzle of the very different tissue specific effects of endocannabinoids (ECs) can be reconstructed in one unitary picture. This picture clearly shows that all the different CB1-mediated effects of ECs sub-serve one major physiological function: to facilitate and increase energy storage. We will also analyze the implications of this unitary vision of the ECS in different contexts. First, in the context of the systems that regulate energy balance, introducing a new systematization based on two homeostatic systems: an endostatic and an exostatic system. Second, in the context of evolution, showing how the function of the ECS has shifted from essential to survival to almost pathological in current times. Finally, in a pathophysiological context, introducing the new concept of "proactive evolution diseases", which can explain the current obesity epidemic and the role the ECS plays in it.
Diabetes Metab 2007 Apr
PMID:Integrated physiology and pathophysiology of CB1-mediated effects of the endocannabinoid system. 1735 Aug 71

Clinical reports (RIO trials) have shown that chronic administration of a CB-cannabinoid receptor antagonist (rimonabant) provides improvements of disturbed metabolic parameters observed in overweight and obese patients with type 2 diabetes. The production of endocannabinoid and the expression of CB1-cannabinoid receptors are largely distributed in the different organs aside from the brain. It is now clearly established that endocannabinoids act both through orexigenic effects and peripheral metabolic effects in various tissues involved in the control of metabolism and energy expenditure (i.e. adipose tissue, liver, gastrointestinal tract, skeletal muscle and pancreas). This review will consider: i) the disturbances of glucose and lipid metabolisms in obese type 2 diabetics; ii) an overview of the pharmacological properties of rimonabant and iii) the various mechanisms involved in tissues and organs to explain the therapeutic efficacy of rimonabant. A special attention will be paid to its utilization in obese type 2 diabetics. The emerging concept of endocannabinoids acting as metabolic regulators is the more likely explanation of the success of rimonabant treatments in phase III studies.
Diabetes Metab 2007 Apr
PMID:Effects of CB1 antagonist on the control of metabolic functions in obese type 2 diabetic patients. 1741 7


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