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

The pancreatic islet hormone secretion is modulated by one or more gastrointestinal peptides ("gut-factor") secreted in response to various types of ingested nutrients. Among a number of postulated candidates for the putative "gut-factor", the gastric inhibitory polypeptide (GIP) has recently emerged as a most likely enteric signal of physiologic import, although its precise role in the pathophysiology of diabetes mellitus remains incompletely understood. During the past decade, an avalanche of knowledge has accumulated regarding a number of peptide agents common to the gastro-enteric-pancreatic system and the nervous system. Preliminary evidence indicates a potential role of several of these peptides in the pathophysiology of diabetes. For instance, cholecystokinin and human pancreatic polypeptide (hPP) may be importantly involved in the regulation of appetite and satiety control and the development of obesity whereas somatostatin, "endorphins", and neurotensin may directly or indirectly modulate islet hormone secretion. Finally the significance of the recently demonstrated presence of insulin and glucagon or glicentin-like peptides in the brain requires close scrutiny.
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PMID:The role of gastrointestinal and neuronal peptides in the pathophysiology of diabetes mellitus. 612 74

Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in rats after ventromedial hypothalamic (VMH) lesions were evaluated by measuring fasting hormone levels and their secretion from the isolated perfused pancreas. Fasting peripheral insulin levels were not altered 1 week after the VMH lesions but became progressively elevated at 3-4, 8-9, and 11-12 weeks compared to the values in sham-operated and age-matched control rats. In the portal vein, insulin levels also progressively increased in VMH-lesioned rats, but the portal-peripheral gradient of insulin in the later phase of VMH obesity was significantly lower than in the early phase after VMH lesions. On the contrary, the arginine-induced insulin release from the perfused pancreas was highest at 1 week and gradually decreased thereafter, although it continued to remain higher than that of controls. The perfusate somatostatin response to arginine also was exaggerated in the VMH-lesioned rats. However, both the peripheral glucagon level and the glucagon secretion from the perfused pancreas of the VMH-lesioned rats were not significantly different from the controls. These results show that VMH lesions result in an increased insulin and somatostatin secretion. Using the cyclically perfused liver in situ, we have found that the hepatic extraction rate of insulin is indeed reduced in rats 8-9 weeks after VMH lesioning, and so have at least partly accounted for the decreased portal-peripheral gradient of insulin in the later VMH postoperative phase.
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PMID:Changes in insulin, somatostatin, and glucagon secretion during the development of obesity in ventromedial hypothalamic-lesioned rats. 614 Jan 60

In the past 10 years, numerous gut peptides have been tested for their satiating effect on food intake. Cholecystokinin (CCK), bombesin, pancreatic glucagon, and somatostatin have the best supporting evidence for such a specific behavioral effect. The satiety effect of CCK, somatostatin, and glucagon is abolished or markedly reduced by abdominal vagotomy, but the satiety effect of bombesin is not. The effect of vagotomy has been interpreted as the result of the loss of vagal afferent fibers that are necessary for carrying information about visceral effects of these peptides to the brain. This hypothesis is under active investigation. There are three reports that CCK decreases the size of a test meal in lean and obese humans. This suggests that CCK or the other peptides may be useful in treating human obesity and bulimia.
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PMID:Gut peptides and postprandial satiety. 614 53

Although the incidence of obesity in the domesticated dog is high, few studies have investigated the regulation of food intake in this species. In the present study we investigated the response of the dog to a number of putative satiety agents including cholecystokinin (CCK), bombesin, calcitonin and naloxone. CCK significantly suppressed food intake during a scheduled fifteen minute meal in intact dogs and in dogs receiving total subdiaphragmatic vagotomies. Emesis occurred following injection of higher doses of CCK in most dogs. Bombesin and calcitonin reduced intake in both normal and vagotomized dogs, although higher doses of calcitonin were needed to significantly suppress feeding in vagotomized dogs compared with intact animals. Naloxone reduced feeding by as much as 60% in intact and vagotomized animals. Glucagon suppressed feeding in intact dogs, but not in vagotomized animals. Somatostatin and pancreatic polypeptide did not alter food intake. Thus the domesticated dog responds somewhat differently to some neuropeptides compared with the laboratory rat stressing the importance of examining the regulation of food intake across species.
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PMID:Peptidergic regulation of feeding in the dog (Canis familiaris). 614 23

Diabetes mellitus in the adult Chinese hamster is characterized by subnormal pancreatic insulin release in vitro, decreased insulin content, and lack of obesity. The cause of the islet B-cell failure is not clear. We measured insulin, glucagon, and somatostatin release from in vitro perfused pancreases of young (mean age 10 and 20 weeks), genetically diabetic animals (subline AC, mean plasma glucose 8.0 and 16.6 mmol/l, respectively). Compared to age- and sex-matched normal hamsters (subline M, mean plasma glucose 5.3 mmol/l), the younger diabetic animals had a significantly elevated mean plasma glucose level, but net in vitro pancreatic release of insulin, glucagon, and somatostatin was normal. Pancreatic content of insulin and glucagon was also not significantly different from normal. At age 20 weeks, when the plasma glucose of the diabetic animals was even more elevated, pancreatic content and release of insulin were significantly subnormal, whereas glucagon and somatostatin release were normal, and pancreatic content of glucagon was normal. In a similar group of young (mean age 10 weeks) diabetic animals, non-fasting plasma insulin levels were within the normal range, but the corresponding glucose levels were excessive in most of the animals (13 out of 19). In conclusion, 10-week-old diabetic hamsters show mild hyperglycaemia which cannot be accounted for directly by decreased pancreatic release in response to a glucose plus arginine stimulus in vitro. Decreased ability of the B cell to respond in vivo to hyperglycaemia or peripheral resistance to insulin may contribute to later B-cell failure in the older diabetic hamster.
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PMID:Insulin, glucagon, and somatostatin release from the prediabetic Chinese hamster. 614 71

Fenfluramine, an anorectic used in the treatment of obesity, in a final concentration of 1 mM strongly inhibited both phases of insulin release by the perfused rat pancreas. Insulin secretion resumed promptly after cessation of the drug infusion. This concentration of the drug markedly increased glucagon output. The blockade of alpha-adrenergic receptors and the use of antiserotonin agents did not alter the inhibitory effect of fenfluramine on insulin secretion. It is concluded that in the perfused rat pancreas 1 mM fenfluramine acutely inhibits glucose-induced insulin secretion and potentiates glucagon output. The direct effect of fenfluramine on insulin secretion is not related to alpha-adrenergic activity, nor is it mediated by serotonin.
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PMID:Fenfluramine inhibits insulin secretion and potentiates glucagon release by the perfused rat pancreas. 622 12

The age-related development of the capacity of the cardiac adenylate cyclase system to be stimulated with secretin, vasoactive intestinal peptide (VIP), glucagon, the beta-adrenergic agonist isoproterenol, Gpp(NH)p, and NaF was compared in obese (fa/fa) Zucker rats and their lean (FA/?) littermates. The obese (fa/fa) Zucker rats tested developed postweaning obesity associated with marked hypertriglyceridemia, mild hyperglycemia, and hyperinsulinism. At 4 weeks, there was already a 57% reduction in secretin-VIP-stimulated adenylate cyclase activity in fa/fa rats. At 12 weeks, the secretin-VIP-stimulation was reduced by 77%, and glucagon- and isoproterenol-stimulations by 16-21%. At 45 weeks, secretin-VIP-stimulation was reduced by 91%, glucagon- and isoproterenol stimulations by 34-42%, and Gpp(NH)p- and NaF-stimulations by 16-23%. The reductions of isoproterenol-, Gpp(NH)p-, and NaF-stimulations were totally or partially reversed in 30-week old fa/fa animals submitted for 5 weeks to severe food restriction that almost normalized the altered blood parameters. In sharp contrast, food restriction imposed a further decrease in secretin-VIP- and glucagon-stimulated adenylate cyclase activities. This pattern of impaired secretin-VIP-stimulated adenylate cyclase activity appeared limited to cardiac membranes in obese animals as the responses of liver, brain and anterior pituitary adenylate cyclase activities to secretin and/or VIP were unaltered. These results suggest that secretin-VIP receptors coupled to adenylate cyclase were rapidly and specifically altered in the heart of fa/fa Zucker rats.
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PMID:Impairment of hormone-stimulated cardiac adenylate cyclase activity in the genetically obese (fa/fa) Zucker rat. 626 81

It is concluded that besides NA, some other hormones (adrenaline, glucagon, growth hormone, ACTH, insulin and adrenal steroids) are also thermogenic. While brown adipose tissue is the most important site of heat during NA thermogenesis, some other organs, namely muscles, also contribute to thermogenesis due to various hormones. Hormones seem to potentiate heat production due to their action in target organs. Humoral thermogenesis not only can compensate the heat loss from the body of cold exposed individuals, but it can also prevent obesity under conditions of an high caloric intake. Some substance, on the other hand, induce a hypometabolic effect (rT3, hibernation trigger, antabolone, bombesin). Additionally, absence of gonadal steroids induce hibernation. Thus, humoral substances contribute both to the control of hyper- and hypometabolic states.
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PMID:Humoral control of hyper- and hypometabolic states. 631 84

Hepatocytes were isolated from 3 and 5 month old female genetically obese Zucker rats and their lean littermate controls. An age-dependent loss in sensitivity of fatty acid synthesis to inhibition by both glucagon and dibutyryl cyclic AMP was observed with hepatocytes from the obese rats. Hepatocytes from lean animals were much more sensitive to these agents, regardless of age. Low concentrations of glucagon and dibutyryl cyclic AMP actually produced some stimulation of fatty acid synthesis with hepatocytes prepared from the older obese rats. 5-Tetradecyloxy-2-furoic acid, a compound which inhibits fatty acid synthesis, was a very effective inhibitor of fatty acid synthesis by hepatocytes isolated from all rats used in the study. An inhibition of lactate plus pyruvate accumulation and a strong stimulation of glycogenolysis occurred in response to both glucagon and dibutyryl cyclic AMP with hepatocytes from both age groups of lean and obese rats. The results suggest that with aging of the obese female Zucker rat some step of hepatic fatty acid synthesis becomes progressively less sensitive to inhibition by glucagon and dibutyryl cyclic AMP. This may play an important role in maintenance of obesity in these animals.
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PMID:Age-related decrease in sensitivity to glucagon and dibutyryl cyclic AMP inhibition of fatty acid synthesis in hepatocytes isolated from obese female Zucker rats. 632 93

Twenty-six patients who were more than 35 per cent above their ideal weight were examined before the introduction of a weight reduction programme. At the end of a three-month period, seven patients had lost more than 10 per cent of their body weight. These patients had significantly lower triglyceride levels, fasting gastric inhibitory polypeptide levels (GIP) and prolactin levels. Fasting vasoactive intestinal polypeptide levels (VIP) before commencing diet were raised in six of the 19 patients who subsequently did not lose weight whereas the seven patients who lost weight had normal VIP levels (X2 = 3.07, P less than 0.05). Patients with high VIP levels had higher triglyceride levels, higher mean C-terminal glucagon-like immunoreactivity (C-GLI) and higher post glucose infusion secretin levels. There was a significant correlation between triglycerides and VIP. The significance of abnormally high VIP levels in obesity and the inability of these patients to lose weight is discussed.
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PMID:Vasoactive intestinal polypeptide in obesity. 634 22


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