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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

Normal, male Sprague-Dawley (S-D) rats and female, lean and obese Zucker rats were studied in the fed state and after 48 hours of food deprivation. Somatostatin-like immunoreactivity (SLI) was measured from acetic acid extracts of oesophagus-cardia, stomach, small and large intestine, pancreas, hypothalamus, pituitary and cerebellum. Within the CNS, the highest levels of SLI were found in the hypothalamus, while in the gut, these levels were highest in the stomach and pancreas. All Zucker rats displayed higher hypothalamic levels of SLI than did S-D rats. Obese Zucker rats in the fed state differed from their lean littermates in that SLI levels were lower in oesophagus-cardia, stomach and hypothalamus, while being higher in pancreas and pituitary. The response to starvation in both obese and lean Zucker rats was qualitatively similar, and included significant increases in stomach and oesophagus-cardia SLI, but with a significant fall hypothalamic SLI. We have concluded that the increase in gastrointestinal SLI with starvation in Zucker as well as in S-D rats may represent a significant regulatory mechanism in nutrient homeostasis. We postulate that gastric SLI may decrease the availability of intestinal insulin secretagogues in the fasting state. This adaptive mechanism appears to be intact in the obese Zucker rat.
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PMID:Starvation increases gastrointestinal somatostatin in normal and obese Zucker rats: a possible regulatory mechanism. 612 4

To investigate some factors that may be related to the hyperinsulinemia of obesity, we measured fractional gastric emptying rates and changes of circulating levels of glucose, insulin, and somatostatin-like immunoreactivity (SLI) following the intragastric instillation of glucose in age-matched obese and nonobese Pima Indians with normal glucose tolerance. Results for the nonobese Pimas were also compared with findings for age- and weight-matched Caucasians with normal glucose tolerance. The levels of fasting plasma insulin and the integrated insulin response to glucose were significantly greater (P less than 0.01) in obese than in nonobese Pimas. Mean rates of fractional gastric emptying, both in the basal state and after the glucose load, were similar for the three groups. The fractional gastric emptying rates after a glucose load were strongly correlated with the integrated responses of both plasma glucose and insulin in the nonobese Caucasians (r = 0.88, 0.90; P less than 0.01) but not in either Pima group. There were no significant differences in peripheral plasma SLI for any of the three groups, either in the basal state or after the glucose load. These findings suggest that the hyperinsulinemia of established obesity is not mediated by alterations in the gastric emptying rate of liquids or by peripheral plasma SLI concentrations. They do not, however, exclude defects in gastric emptying of solid foods. Nor do they exclude the possibility that gastric or D-cell abnormalities exist during the period of fat accumulation but recede after obesity is established.
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PMID:Hyperinsulinemia in obesity: lack of relation to gastric emptying of glucose solution or to plasma somatostatin levels. 613 35

Using a combined infusion of somatostatin, insulin and glucose, insulin resistance was assessed in vivo in two groups of females with polycystic ovaries (PCO), obese (PB-PCO) and normal weight (NO-PCO) and in two groups of matched (for age, sex and body mass index) controls (OB and NO). A steady state plasma glucose (SSPG) and insulin (SSPI) was attained after 90 min. OB-PCO and NO-PCO showed higher SSPG with respect to matched controls. The SSPG levels were related to body mass index (r = 0.69; P less than 0.001). The SSPG values were significantly correlated with the fasting insulin levels (r = 0.47; P less than 0.003). Gonadotrophin and steroid peripheral blood concentrations were also evaluated in the PCO females. A significant correlation was found between the SSPG values and the dehydroepiandrosterone sulphate levels (r = 0.46; P less than 0.05) and between the fasting insulin levels and the androstenedione concentrations (r = 0.64; P less than 0.01). Moreover, significant correlation coefficients were found between the glucose to insulin ratio and the A (r = -0.59; P less than 0.01) and the DHEA-S (r = -0.50; P less than 0.05) plasma levels. Finally, no relationship between body mass index and A or DHEA-S levels was found in PCO females considered as a group. We conclude that insulin resistance is present in females with PCO and it is mainly due to the presence of obesity, but other factors such as androgen levels, probably of adrenal sources, must be considered as a cause.
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PMID:Insulin resistance in patients with polycystic ovaries: its relationship to body weight and androgen levels. 613 24

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

Skeletal muscle sensitivity and responsiveness to insulin and their relationship to overall glucose disposal and insulin binding were determined in 89 premenopausal women of varying body fat topography (waist/hips girth ratio [WHR] 0.64-1.02) and obesity level (percentage of ideal body weight 92-230). As a marker of insulin action, the percentage of total glycogen synthase present in the I form (glucose-6-phosphate independent) was measured in quadriceps muscle biopsies. The increase in percentage of synthase I 1 h after oral glucose loading was not significantly different between nonobese and obese weight-matched subgroups of increasing WHR, but this response was maintained at the expense of increasing plasma insulin levels as the WHR rose. The increase in percentage of synthase I in response to submaximal steady state plasma insulin (SSPI) of approximately 100 microU/ml achieved by the infusion of somatostatin, insulin, and glucose, however, was significantly lower in obese than in nonobese subjects, and was inversely correlated with WHR. The increase in percentage of synthase I correlated inversely with the steady state plasma glucose (SSPG) concentration, which is an index of the efficiency of overall glucose disposal, and directly with insulin binding to circulating monocytes. Insulin binding also correlated inversely with WHR and with fasting plasma insulin levels. When obese subjects were separated into three weight-matched subgroups on the basis of increasing WHR, significant trends to decreased percentage of synthase I response, increased SSPG, and decreased insulin binding were found. In women with predominantly upper body obesity (WHR greater than 0.85), the increase in percentage of synthase in response to submaximal SSPI was diminished, but there was no impairment of percentage of synthase I responsiveness to supramaximal SSPI of approximately 1,000 microU/ml. At supramaximal SSPI levels, SSPG in four obese women was normal, whereas in five women, SSPG concentrations were markedly increased. Our results suggest that in premenopausal women, impaired skeletal muscle insulin sensitivity that results in decreased glucose storage capacity may contribute to the diminished efficiency of glucose disposal and insulin resistance that are associated with upper body obesity. The impairment in skeletal muscle sensitivity may be overcome in vivo at the expense of increasing plasma insulin levels, with maximal responsiveness remaining unimpaired. This defect may result from a reduction in insulin receptor number which could, in turn, be secondary to persistently elevated fasting plasma insulin levels. In some upper body segment obese women, however, an additional defect affecting other insulin-sensitive pathways may also be present.
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PMID:Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. 614 58

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

A possible role for increased androgenic/estrogenic activity in the pathogenesis of upper body fat localization and its accompanying cellular and metabolic characteristics was examined. Eighty healthy, nonhirsute, premenopausal, caucasian women with a wide range of body fat topography [waist to hips girth ratio (WHR), 0.64 to 1.02] and obesity level (percentage of ideal body weight, 92-251%) were studied. Increasing androgenicity, as reflected by a decrease in plasma sex hormone-binding globulin capacity and an increase in the percentage of free testosterone, was accompanied by 1) increasing WHR, this relationship being independent of and additive to that of obesity level; 2) increasing size of abdominal, but not femoral, adipocytes; 3) increasing plasma glucose and insulin levels, both basally and in response to oral glucose loading; and 4) diminished in vivo insulin sensitivity, as revealed by increasing steady state plasma glucose levels at comparable plasma insulin levels, attained by the infusion of somatostatin, insulin, and glucose. No association was found between total plasma testosterone, androstenedione, dehydroepiandrosterone sulfate, or estradiol concentrations and WHR, fat cell size, or metabolic profiles. We, therefore, propose that in premenopausal women, a relative increase in tissue exposure to unbound androgens may be responsible in part for localization of fat in the upper body, enlargement of abdominal adipocytes, and the accompanying imbalance in glucose-insulin homeostasis.
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PMID:Relationship of androgenic activity to body fat topography, fat cell morphology, and metabolic aberrations in premenopausal women. 634 69


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