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

Administration of alloxan to rats which developed hypothalamic adiposity damaged the pancreatic beta-cells and reduced the insulin secretion, thus arresting further weight gain despite some excess in food ingestion. A conclusion was drawn that in injury of the ventro-medial nuclei of the hypothalamus the most significant mechanism of obesity development was insulin hypersecretion induced by this action.
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PMID:[Role of the endocrine function of the islands of Langerhans in the mechanism of development of hypothalamic obesity]. 80 Sep 55

A new automated potentiometric method for the determination of colipase was developed, taking advantage of the reactivation of purified lipase, in the presence of bile salt and at pH 6.5. High-fat and high-starch diets induced an opposite regulation of lipase and amylase in the rat pancreas. At the same time, the level of colipase was not influenced by nutrition. During fasting and in alloxan diabetes, the specific activity of lipase almost doubled, that of amylase decreased sharply, and colipase was not affected in the rat pancreas. In obese-hyperglycemic mice, suffering from obesity, hyperinsulinism, and moderate diabetes, there was also no regulation of pancreatic colipase. Thus, at variance with a number of hydrolases, there was no dietary or hormonal adaptation of colipase. However, this was probably without any bearing on intraluminal lipolysis. Indeed, comparison of lipase and colipase activities in pancreas and in small intestine suggests that colipase concentration is not a limiting factor of intraluminal lipolysis. The molecular mechanism of this assumption is discussed on the basis of in vitro studies.
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PMID:Lack of adaptation of pancreatic colipase in rats and mice. 84 20

ALS and ALR mice were developed as mouse models of alloxan-induced diabetes. These strains do not show spontaneous onset of diabetes. When an obesity gene (Ay) was introduced to these two strains, severe diabetic conditions occurred spontaneously in the produced ALS-Ay and ALR-Ay strains. These strains were examined body weight gain, food consumption, water consumption, urinary sugar content, ketone body level and blood sugar level, and subjected to glucose tolerance test. As a result, in comparison with ALS mice, male ALS-Ay mice showed no obesity and very low tolerance to the glucose tolerance test performed 24 weeks after birth. The level of insulin secretion was 5.0 microU/ml or less, showing hardly any secretory reaction. On the other hand, female ALS-Ay mice were obese and showed no marked decrease in glucose tolerance. The level of insulin secretion was high, and the secretory reaction was strong. In ALR-Ay strain, both male and female mice were obese and showed diabetic conditions similar to those of ALS-Ay mice, though the severity tended to be lower. The characteristic features of diabetic conditions in these mice suggest that these strains, particularly ALS-Ay, may serve as useful new-type models of diabetes.
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PMID:[Diabetic peculiarity of the ALS-Ay and ALR-Ay strains]. 191 99

We studied the lipase and colipase activity in pancreatic acinar tissue of insulin-deficiency and insulin-resistance obese Zucker rats (fa/fa). After injection of streptozotocin (STX 75 mg/kg) in normal Sprague-Dawley rats, the activity of lipase and colipase in pancreatic acinar tissue was increased by approximately 100%, the increase in colipase occurring 3 days later than that of lipase. At the same time, the amylase activity was decreased by 98%. Injection of alloxan (125 mg/kg) induced a similar change of pancreatic enzyme pattern, with amylase activity strongly reduced by 79% and activity of lipase and colipase increased 20.5 and 18.6%, respectively. Correction of the diabetic state with insulin (1 U/100 g/day) reversed the activity of these enzymes to their prediabetic levels. Administration of insulin (6 U/100 g/day) to normal Sprague-Dawley rats increased the activity of amylase as well as lipase and colipase, whereas injection of glucagon (0.3 mg/100 g/day) decreased the activity of amylase and colipase but had no significant effect on lipase activity. In the obese Zucker rats (fa/fa), the activity of lipase and colipase at onset of obesity (5 weeks of age) was lower than that in their lean littermates (fa/o). Thereafter the activity of the two proteins increased with age, being 40% higher in the fa/fa rat than in the fa/o rat at age 7 weeks. During the same period, amylase activity decreased. These results indicate that pancreatic lipase and colipase activity are increased following either insulin deficiency or insulin resistance in rats by a mechanism related to the changed levels of insulin.
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PMID:Pancreatic lipase and colipase activity increase in pancreatic acinar tissue of diabetic rats. 247 69

Obese and lean Zucker rats were made diabetic by intracardiac injections of alloxan (65-72 mg/kg body weight) and then given daily injections of protamine zinc insulin [1.25 U/(100 g/d)] for 6, 9 and 12 d. Body weight, food intake, plasma glucose and immunoreactive insulin concentrations were not different for lean and obese diabetic rats of similar ages. Rates of increase in carcass protein, mixed muscle protein and myofibrillar protein were less in obese than in lean rats. However, rates of increase for the sarcoplasmic fraction were not different. Fractional rates of synthesis of total muscle protein and myofibrillar protein, as determined by continuous intravenous infusion of [14C]tyrosine, were comparable in the two genotypes. Fractional rate of myofibrillar protein degradation, as determined by urinary 3-methylhistidine excretion, was higher in obese than in lean rats. Differences in calculated absolute rates between genotypes did not parallel differences in the fractional rates, due mainly to a smaller protein mass in obese rats. As a consequence, absolute synthetic rates were lower in obese rats, while absolute degradation rates were similar in the two genotypes. In contrast, rates of liver protein synthesis were similar in obese and lean rats, whether expressed as fractional or absolute rates. These results indicate that decreased protein deposition in the obese animal is a consequence of both an absolute decrease in protein synthesis in muscle as well as a disproportionately elevated protein degradation in muscle. Hyperinsulinemia normally seen in obese rats may be an adaptive response to minimize the impaired balance between protein synthesis and degradation.
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PMID:Protein turnover in insulin-treated, alloxan-diabetic lean and obese Zucker rats. 389 2

Male, 5 months old, massively obese, spontaneously hypertensive rats (Obese/SHR) were given 10 mg alloxan/100 g b.w., s.c., to induce diabetes. Control Obese and non-obese/SHR were given saline. Insulin therapy was withheld. All of the animals were killed at 6 months of age. Alloxan caused a slight but statistically significant increase in blood pressure, pituitary and adrenal glandular hyperplasia, hyperlipidemia, hyperglycemia, and increased BUN levels. The giant sized islets of Langerhans in Obese/SHR showed only partial degranulation of the insulin-producing beta cells concomitant with residual but apparently adequate blood insulin levels, whereas the islets of non-obese/SHR exhibited virtually total beta cell degranulation and only trace amounts of blood insulin. The alloxanized, non-obese rats were severely emaciated; the alloxanized Obese/SHR maintained their obesity. Alloxan-treated, Obese and non-obese/SHR manifested gross and microscopic degenerative changes suggesting acceleration of the normal aging process. The genetically-programmed pathogenesis of diabetes, obesity, hypertension, and Cushingoid pathophysiology of Obese/SHR may be due to hyperadrenocorticism.
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PMID:Resistance of obese and non-obese, spontaneously hypertensive rats to alloxan-induced diabetes. 635 Jul 80

In summary, the present review provides evidence in support of the proposition that pancreatic islet cell hyperplasia precedes the development of insulin insensitivity in the obese mouse and, it is likely, that similar events occur in obese humans. Moreover, the hyperplastic pancreatic islet appears to be responsible for the development of insulin insensitivity, since suppression of the hyperplastic islet, by either alloxan or streptozotocin administration to the obese mouse, results in amelioration of insulin insensitivity in vivo. Since no change occurred in the degree of obesity or in adipocyte cell size or number, it is evident that insulin sensitivity is independent of obesity per se. Hence, although obesity and insulin insensitivity frequently co-exist, insulin insensitivity is independent of obesity and is due rather to the presence of pancreatic islet cell hyperplasia. Light and electron microscopy of the hyperplastic pancreatic islets of the obese mouse reveal increased numbers of A- B- and D-cells. Islet suppression with alloxan or streptozotocin results in the selective reduction of B-cells with preservation of A- and D-cells. Therefore, restoration of insulin sensitivity in the obese mouse following pancreatic islet cell suppression appears to be directly related to suppression of B-cell hypersecretion. Biochemical studies of muscle and adipose tissues from the obese mouse reveal profound insulin unresponsiveness without clear cut improvement in vitro following pancreatic islet cell suppression and restoration of insulin sensitivity in vivo. These data are consistent with a relatively modest reduction in the number of available insulin receptors upon these tissues in relation to the marked insulin resistance and imply an impairment of insulin action beyond the insulin receptor interaction [either transport or intracellular action(s)] as the major site(s) of insulin resistance in the muscle and adipose tissues of obese mice. Conversely a reduction of insulin receptors upon hepatocytes of obese mice and their improvement following a reduction of B-cell hypersecretion support the proposition that the number of available insulin receptors may be the major site for the regulation of insulin action upon that tissue. Finally, evidence is presented which suggests that an inability of insulin to limit hepatic gluconeogenesis may be the predominant cause of insulin insensitivity in the obese mouse.
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PMID:The relationship between the hyperplastic pancreatic islet and insulin insensitivity in obesity. 645 13

Obese and lean alloxan-diabetic rats were given daily injections of insulin for 9 days. Plasma glucose and insulin concentrations were not different between the two genotypes given comparable amounts of insulin. Carcass fat and epididymal and retroperitoneal fat pad weights increased as the dose of insulin was increased. At each of four doses, fatties had larger fat cells, bigger pads, and more body fat than lean rats. Adipose lipoprotein lipase (LPL) activity per pad or per fat cell was increased by insulin. Except for the lowest dose of insulin, LPL activity was higher in obese rats than in lean rats. LPL activity per cell and cell size were highly correlated. However, when differences in cell size were corrected for, no significant effect of genotype existed. Cardiac LPL activities were different between the two genotypes only in nondiabetic rats. These results suggested that both insulin and some other genetic factors were important in elevating adipose LPL activities and thus fat deposition in obese Zucker rats.
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PMID:Adipose lipoprotein lipase in insulin-treated diabetic lean and obese Zucker rats. 704 62

Five-week-old male obese and lean Zucker rats were made comparably diabetic by intracardiac injections of alloxan (65-72 mg/kg body wt). Lean rats were then given daily injections of protamine zinc insulin at 3 doses: 0.25, 1.25, and 4.0 U.100 g body wt-1.day-1 for 3 wk. Obese rats received identical amounts as corresponding lean controls independent of body weights. The drop of blood glucose concentration after injections of regular insulin and the percentage fall in radioactive plasma insulin after injections of 125I-insulin were comparable in lean and obese rats. Weight gain, fat gain, and protein gain over 21 days increased with increasing amounts of insulin administered. However, at the same dose of insulin, although weight gain was comparable, fat gain was higher and protein gain was lower in obese rats when compared to lean controls. These results suggest that the enhanced lipid deposition of the obese Zucker rat is not totally dependent on insulin levels, but is exaggerated by hyperinsulinemia.
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PMID:Effect of insulin on fat and protein deposition in diabetic lean and obese rats. 705 84

The metabolism of neutral lipids (free and ester-bound cholesterols, mono-, di- and triacylglycerides) was greatly impaired in liver, spleen, thymus tissues and ileocecal lymph nodes of BALB/c mice with subacute alloxan diabetes (content of sugar in blood was no less than 14 mmol/l) as shown by 3H-acetate and 14C-palmitate incorporation into the corresponding lipid fractions. The rate of neutral lipid turnover was specifically decreased in all the tissues studied. However, a considerable accumulation of these lipid fractions was found in thymus tissue. Incorporation of labelled palmitate into triacylglycerides was increased in the spleen but without obesity of the organ.
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PMID:[Metabolism of neutral lipids in hemopoietic organs and in the liver of mice with alloxan diabetes]. 783 58


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