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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pharmacological treatment of obesity has been neglected as a viable therapeutic option for many years. Recent long term studies with combinations of obesity drugs gives promise that drugs may play a role in weight maintenance, which classically has been the most difficult aspect of treating obesity. Currently available obesity drugs include centrally acting adrenergic agents and serotonin agonists. Drugs still in development include a lipase inhibitor that produces fat malabsorption, a combined adrenergic-serotonergic reuptake inhibitor, various gut-central nervous system peptides, and a number of beta-3 agonists. Any of these obesity drugs given alone produces modest weight loss, and for most, weight loss continues for as long as medication is given. The most successful drug regimens to date are combinations of phentermine and fenfluramine or of ephedrine, caffeine, and/or aspirin. The former combination produces reduction in body weight and complications of obesity for 2 to almost 4 years in clinical trials to date. More research is needed to document long term efficacy and particularly the long term safety of these and other combinations.
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PMID:Combined drug treatment of obesity. 869 49

Non-insulin-dependent diabetes (NIDDM) is a common problem in the elderly. The discovery of several classes of oral antidiabetic agents has increased the prospects of achieving better control of hyperglycaemia with reduced risk of severe adverse events. Some of these agents, such as acarbose or miglitol, do not cause hypoglycaemia and act locally in the gut. As such they are safer agents. On the other hand, the low cost of some sulphonylurea agents and a once or twice daily administration schedule make them an attractive option. Metformin appears to be especially useful in obese insulin-resistant patients with NIDDM. However, obesity is not as much of a problem in the elderly as it is in middle-aged patients, and contraindications to the use of metformin are common in the elderly. The use of a combination of 2 or 3 oral antidiabetic agents to delay the need for insulin therapy is now possible. The long term effects of this approach are not known and the cost of polypharmacy is of concern.
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PMID:Drug therapy of non-insulin-dependent diabetes mellitus in the elderly. 873 15

Glucagon-like peptide 1 (GLP1) is postulated to regulate blood glucose and satiety, but the biological importance of GLP1 as an incretin and neuropeptide remains controversal. The regulation of nutrient-induced insulin secretion is dependent on the secretion of incretins, gut-derived peptides that potentiate insulin secretion from the pancreatic islets. To ascertain the relative physiological importance of GLP1 as a regulator of feeding behavior and insulin secretion, we have generated mice with a targeted disruption of the GLP1 receptor gene (GLP1R). These GLP1R-/- mice are viable, develop normally but exhibit increased levels of blood glucose following oral glucose challenge in association with diminished levels of circulating insulin. It is surprising that they also exhibit abnormal levels of blood glucose following intraperitoneal glucose challenge. Intracerebroventricular administration of GLP1 inhibited feeding in wild-type mice but not in GLP1R-/- mice; however, no evidence for abnormal body weight or feeding behavior was observed in GLP1R-/- mice. These observations demonstrate that GLP1 plays a central role in the regulation of glycemia; however, disruption of GLP1/GLP1R signaling in the central nervous system is not associated with perturbation of feeding behavior or obesity in vivo.
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PMID:Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. 889 56

The object of this study was to examine whether eating behavior, food preference, gastric emptying, and gut hormone patterns are altered after jejunoileal bypass (JIB) in patients with severe obesity. Eight obese [mean (+/- SD) body mass index (BMI; in kg/m2) 42.9 +/- 4] subjects were studied prospectively before and 9 mo after JIB with eight age- and sex-matched normal-weight control subjects. Total energy intake, data from the universal eating monitor (VIKTOR), eating motivation measured by visual analog scales, a food-preference checklist, a forced-choice list, solid-phase gastric emptying, and postprandial concentrations of cholecystokinin, motilin, and neurotensin were studied. BMI was reduced by 29% after JIB. Compared with normal subjects, the JIB patients showed a reduced desire to eat, decreased hunger, and reduced prospective consumption before a test meal. After surgery, obese subjects selected fewer food items and showed a reduced preference for high-carbohydrate and high-fat items before a test meal. There was a trend from an accelerated toward a decelerated eating pattern in obese subjects after JIB. After JIB, gastric emptying of obese subjects was slowed and similar to that in control subjects. Obese subjects had lower postprandial cholecystokinin concentrations that were lower than those of control subjects both before and after JIB. Postprandial concentrations of neurotensin were higher after JIB. We conclude that after JIB, the desire to eat and preference for high-carbohydrate and high-fat items is reduced, resulting in decreased energy intake. That gastric emptying is prolonged and gut hormone patterns are altered with low postprandial plasma cholecystokinin and high neurotensin plasma concentrations may at least partly account for these observations.
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PMID:Reduced food intake after jejunoileal bypass: a possible association with prolonged gastric emptying and altered gut hormone patterns. 920 88

Glucagon-like peptide 1 (GLP-1) is a physiological incretin hormone in normal humans explaining in part the augmented insulin response after oral versus intravenous glucose administration. In addition, GLP-1 also lowers glucagon concentrations, slows gastric emptying, stimulates (pro)insulin biosynthesis, reduces food intake upon intracerebroventricular administration in animals, and may, in addition, enhance insulin sensitivity. Therefore, GLP-1, in many aspects, opposes the Type 2-diabetic phenotype characterized by disturbed glucose-induced insulin secretory capacity, hyperglucagonaemia, moderate insulin deficiency, accelerated gastric emptying, overeating (obesity) and insulin resistance. The other incretin hormone, gastric inhibitory polypeptide (GIP), has lost almost all its activity in Type 2-diabetic patients. In contrast, GLP-1 glucose-dependently stimulates insulin secretion in diet- and sulfonylurea-treated Type 2-diabetic patients and also in patients under insulin therapy long after sulfonylurea secondary failure. Exogenous administration of GLP-1 ([7-37] or [7-36 amide]) in doses elevating plasma concentrations to approximately 3-4 fold physiological postprandial levels fully normalizes fasting hyperglycaemia in Type 2-diabetic patients. The half life of GLP-1 is too short to maintain therapeutic plasma levels for sufficient periods by subcutaneous injections. Current research activities aim at finding GLP-1 analogues with more suitable pharmacokinetic properties than the original peptide. Another approach could be the augmentation of endogenous release of GLP-1, which is abundant in L cells of the lower small intestine and the colon. Interference with sucrose digestion using alpha-glucosidase inhibition moves nutrients into distal parts of the gastrointestinal tract and, thereby, prolongs and augments GLP-1 release. Enprostil, a prostaglandin E2 analogue, fully suppresses GIP responses, while only marginally affecting insulin secretion and glucose tolerance after oral glucose, suggesting compensatory hypersecretion of additional insulinotropic peptides, possibly including GLP-1. Given the large amount of GLP-1 present in L cells, it appears worthwhile to look for more agents that could 'mobilize' this endogenous pool of the 'antidiabetogenic' gut hormone GLP-1.
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PMID:Glucagon-like peptide 1 (GLP-1) as a new therapeutic approach for type 2-diabetes. 928 4

Type II diabetes is a common disorder whose prevalence is increasing in the United States and throughout the world. Type II diabetes is also associated with several other metabolic abnormalities such as central obesity, hypertension, and dyslipidemia, which contributes to the very high rate of cardiovascular morbidity and mortality. The main pathologic defects in diabetes consist of excessive hepatic glucose production, peripheral insulin resistance, and defective beta-cell secretory function. The duration and severity of the hyperglycemia dictate the microvascular complications, no matter what the etiology of the glucose intolerance, and the goals of therapy should be similar to those of insulin-dependent type I diabetic patients. Initiation of nonpharmacologic therapy should be started as soon as the diagnosis is made. Pharmacologic agents should be initiated if the glycemic goals are not met with a 3-month trial of diet and exercise. The cornerstone of therapy consists of a regular exercise routine along with a diet consisting of 40% to 50% complex carbohydrates, 10% to 20% protein, and monounsaturated fats such as canola oil and olive oil. If nonpharmacologic therapy does not achieve adequate glycemic control, initiation of an oral antidiabetic agent is warranted. In addition to the sulfonylureas, which work by stimulating insulin secretion, we now have metformin, which inhibits excessive hepatic glucose production; acarbose, which delays the absorption of carbohydrates in the gut; and troglitazone, which reduces insulin, resistance primarily in skeletal muscle. The selection of an initial oral antidiabetic agent depends on patient characteristics such as the presence of obesity and dyslipidemia, the duration of diabetes, and other concomitant conditions. Combination therapy with two or three of the different classes of oral antidiabetic agents is effective and has been used throughout the world. When maximum doses of oral antidiabetic agents do not adequately control glycemia, insulin therapy is necessary. In selected patients, combination therapy consisting of bedtime intermediate-acting insulin in addition to daytime oral antidiabetic agent(s) can be an effective method to normalize glucose control without the need for rigorous insulin regimens. When combination therapy fails, a split-mixed regimen using premixed 70/30 insulin prebreakfast and predinner can be very effective in obese subjects. In thin insulin-requiring subjects with type II diabetes, more intensive regimens may be required. In general, the risk of severe hypoglycemia is quite low in patients with type II diabetes, and the main adverse effect of insulin therapy is weight gain. Prevention and aggressive treatment of glucose intolerance and the other adverse metabolic conditions associated with type II diabetes will not only have a positive effect on the quality of life but also provide long-term cost savings.
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PMID:Type II diabetes mellitus. 950 90

The effects of inclusion of different levels of raw kidney bean (Phaseolus vulgaris) of high lectin content (27 g/kg meal) in a high-quality (lactalbumin) control diet were tested in nutritional trials on the growth and metabolism of obese Zucker (fafa) rats and their lean littermates in comparison with pair-fed controls. All diets contained 100 g total protein/kg and either 50 g lipids/kg (low fat) or 150 g lipids/kg (moderate fat). The growth of both obese and lean rats on bean diets was retarded by the daily bean intake in a dose-dependent manner. However, most of this was because bean-fed rats contained less body fat than the controls after 10 d. Thus, after feeding low-fat diets containing up to 130 g kidney bean/kg (lectin intake < or = 0.2 g/kg body weight (BW) per d) in both 10 d and 70 d trials, the bodies of obese rats contained less fat but not protein than their pair-fed controls. Moreover, by increasing the lipid content of the diet to 150 g/kg, the level of bean inclusion could be increased to 280 g/kg (lectin intake > or = 0.4 g/kg BW per d) without loss of body protein and skeletal muscle. Although these rats contained more body fat than those which were fed on low-fat diets, their weight reduction could be accounted for exclusively by reduced lipid content. In contrast, significant body protein loss occurred when the same diet of high lectin content was fed to lean littermates. Plasma insulin levels were significantly depressed in the obese Zucker rats on bean diets but the pancreas was not significantly enlarged nor its insulin content changed in 10 d trials. However, significant pancreatic growth occurred on long-term (70 d) bean feeding compared with pair-fed controls. The results suggest that, in addition to animal nutrition, it may also be possible to use the bean lectin as a dietary adjunct or therapeutic agent to stimulate gut function and ameliorate obesity if a safe and effective dose-range can be established for human subjects.
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PMID:Lipid accumulation in obese Zucker rats is reduced by inclusion of raw kidney bean (Phaseolus vulgaris) in the diet. 953 66

The pancreatic polypeptide (PP-fold) family of peptides consists of the endocrine peptides, pancreatic polypeptide (PP) and peptide YY (PYY), and the neuroneally derived peptide, neuropeptide Y (NPY). All three peptides are found in the circulation, with PP found primarily in the pancreas and PYY found principally in the gut. NPY is released into the circulation from neuroneal stores in response to stress. These peptides have broad peripheral actions on a number of organs. Not surprisingly, PYY and PP are believed to play an important role in the function of the gastrointestinal tract while NPY is a potent vasconstrictor and may have effects on the gut through the enteric nervous system. In the brain, NPY has been implicated in anxiety and depression, feeding and obesity, memory retention, neuroneal excitability, endocrine function, and metabolism. Recent advances in the molecular biology of the receptors for these peptides have resulted in the identification of at least six receptor subtypes with varying peptide pharmacology. Compared to other G-protein coupled receptor families, the PP-fold peptide receptors exhibit a relatively low level of sequence identity. Further advances in the development of selective agonists and antagonists for individual receptor subtypes will be needed to understand further their role in physiological function.
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PMID:Multiple receptors for the pancreatic polypeptide (PP-fold) family: physiological implications. 957 48

Obese hyperglycemic mice have large pancreatic islets and high levels of serum insulin and blood glucose. Vagotomy was performed on 3-wk-old animals to investigate the role of gut cholinergic innervation in young Umea ob/ob mice. After vagotomy, obesity and hyperglycemia are dissociated. Weight increase in obese vagotomized mice was lower than in sham-operated controls during the 1st wk postoperatively but not thereafter. Blood glucose was lower up to 5 mo after vagotomy, but vagotomized mice showed reduced glucose tolerance. Islet cell proliferation rate was reduced 2 and 3 wk but not 5 mo after vagotomy. After 5 mo, islet volume was smaller in vagotomized mice. Serum insulin levels were the same in vagotomized animals as in sham-operated controls. The effects of reduced cholinergic innervation are probably caused both by direct effects of denervation and by lowered metabolic demand.
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PMID:Vagotomy in young obese hyperglycemic mice: effects on syndrome development and islet proliferation. 961 Nov 53

The gut peptide glucagon-like peptide 1(7-36) amide (GLP-1) is released into the circulation after food intake. GLP-1 has been shown to have an incretin effect and inhibits gastrointestinal motility in humans. In rats, intracerebral administration of GLP-1 results in reduced food intake. Obese humans have been found to have an attenuated plasma GLP-1 response to a mixed meal. To approximate the physiologic state, GLP-1 or saline was administered intravenously and randomly at the beginning of a test meal served on a universal eating monitor to 6 obese subjects to test our hypothesis that GLP-1 influences termination of food intake (and thus food intake during a meal) and feelings of satiety in humans. As a marker for gastric emptying, 1.5 g acetaminophen was given at the start of the meal. Blood samples for analysis of acetaminophen, insulin, glucose, glucagon, and C-peptide were obtained. Hunger, fullness, and food choice were assessed with visual analogue scales and food-choice questionnaires. GLP-1 infusion resulted in a prolonged period of reduced feelings of hunger, desire to eat, and prospective consumption after the meal. The rate of gastric emptying was slower during infusion of GLP-1. Postprandial blood glucose concentrations were reduced during the GLP-1 infusion, but the amount of energy consumed, eating rate, and plasma concentrations of insulin, glucagon, and C-peptide were unchanged. GLP-1 given exogenously at the start of a meal did not seem to affect meal termination or the amount of food eaten. However, postprandial feelings of hunger decreased, suggesting that exogenous GLP-1 may influence feelings of hunger and satiety in humans.
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PMID:Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. 973 26


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