Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether hyperglycemia in the obese hyperglycemic (ob/ob) mouse is related to enhanced activity of the pancreatic beta cell, streptozotocin (175 mg/kg) was injected into lean and ob/ob mice at 8 wk of age. The influence of this injection upon glucose metabolism, adipose cellularity, pancreatic morphology and immunoreactive insulin (IRI) release from isolated pancreatic islets was measured. The plasma glucose levels before and after an oral glucose load were elevated in lean and decreased in ob/ob mice 2 wk after treatment with streptozotocin. By 5 wk after this treatment, a reduced pancreatic islet size, beta cell number and a decreased pancreatic islet IRI release were present in both lean and ob/ob mice. At this time, plasma glucose was still elevated in lean, but depressed in ob/ob mice and the insulin responsiveness in muscle and adipocytes was unchanged. Hyperglycemia abates in the ob/ob mouse as hypersecretion of insulin is diminished, but these observations may not be directly related, since streptozotocin affects key metabolic activities of the livers as well as the pancreatic beta cell. The progression of obesity and status of adipose cellularity are not directly related to hyper-insulinemia, since they are not altered following streptozotocin treatment.
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PMID:Effects of streptozotocin on glucose metabolism, insulin response, and adiposity in ob/ob mice. 12 52

Glycerokinase activity in isolated fat cells was elevated in both Ob/Ob and Db/Db mice in comparison to their lean controls and this elevation was associated with obesity, hyperinsulinemia and hyperglycemia. In the other forms of acquired and genetic obesity in the rats and mice studied (also associated with hyperinsulinemia), adipose tissue glycerokinase activity was not elevated in comparison to lean control groups when expressed on a mg protein basis. It is concluded that the elevated glycerokinase activity is not due to the specific Db or Ob mutation, but is secondary to the obesity and hyperinsulinemia interacting with the similar genetic background in the C57BL/KsJ and the C57BL/6J mouse strains.
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PMID:Adipose tissue glycerokinase activity in genetic and acquired obesity in rats and mice. 16 46

Mutation diabetes in the mouse occurs in the C57BL/Ks strain. All homozygous animals (db/db) develop obesity, elevated blood sugar levels and increased or normal blood insulin concentration. The defects in cellular immunity in db/db mice and their littermate controls were examined both in vivo and in vitro. Significant suppression of delayed footpad swelling and first and second set skin allograft rejection time were observed. In addition, DNA synthesis in spleen cells after nonspecific mitogen stimulation was markedly inhibited. Diabetic animals with a mean blood sugar of 512 +/- 101 mg/100 ml did not respond to exogenous insulin therapy by lowering their blood sugar levels or reversing the defect in DNA synthesis. Adding insulin to spleen cell culture in vitro had no demonstrable effect on their response to mitogens. Thus, mutation diabetic mice with their known defect in the peripheral utilization of insulin have markedly suppressed cell-mediated immune mechanisms.
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PMID:Impairment of cell-mediated immunity in mutation diabetic mice (db/db). 34 1

A new strain of obese mouse, the PBB/Ld, has been studied in terms of fat pad cellularity, serum insulin and blood glucose levels, and response to gold thioglucose injections. Age-matched C57B1/6J mice were used as controls. Adipocyte size and number in the major fat depots were determined at various ages from weanling to maturity in the PBB/Ld and C57B1/6J strains. Results indicated that obesity in the PBB/Ld was due to hypertrophy of adipocytes in retroperitoneal and subcutaneous fat depots and to hypertrophy and hyperplasia in the epididymal fat pad. PBB/Ld mice also developed hyperinsulinemia and hyperglycemia and these findings have been discussed in terms of the developmental changes in fat pad cellularity. The injection of gold thioglucose led to increased food intake in both PBB/Ld and C57B1/6J mice. Hyperphagia was also present in the PBB/LD control group, but increased efficiency of converting calories to body weight was not observed in this group when compared to control C57B1/6J mice. The characteristics of obesity seen in the PBB/Ld mouse are discussed and comparisons are made to similar studies in other rodent models of obesity.
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PMID:Description of obesity in the PBB/Ld mouse. 34 7

A longitudinal in vivo and in vitro analysis of the genesis of insulin resistance has been carried out in mice made obese by chemical made obese by chemical lesion (goldthioglucose, GTG) of the hypothalamus. Six weeks after GTG administration, glycemia and glucose disposal were normal but associated with increased insulin concentration, suggesting incipient insulin resistance. The in vitro counterpart of the latter in obese mice was observed in soleus muscle that was somewhat less responsive to insulin than controls, in liver that had increased basal lipogenesis but was uninfluenced by insulin, and in hepatic plasma membranes in which a slight decrease of insulin binding was measured. At this stage of obesity, basal adipose tissue lipogenesis was increased but the tissue responded in a normal fashion to insulin. These relatively discrete early metabolic changes were corroborated in vivo by a normal hypoglycemic effect of exogenous insulin. Sixteen weeks after GTG administration, hyperglycemia and gross hyperinsulinemia were recorded. This insulin resistance was evidenced in vivo by the lack of hypoglycemic effect of exogenous insulin unless considerable amounts of the hormone were administered. It coincided in vitro with a poor response of soleus muscle to insulin, an absence of a stimulatory effect of the hormone upon both adipose tissue and liver tissue, and a marked decrease in insulin binding to liver plasma membranes. It appears that insulin resistance is a multifactorial and progressive abnormality that might involve both insulin receptor and intracellular metabolic alterations.
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PMID:Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. 36 21

Five nonalcoholic diabetic women were clinically and histologically verified as having micronodular cirrhosis. In this series all the patients were over 50 years of age, and showed obesity, hyperglycemia, enlarged liver and mild abnormalities of liver function tests. The histological findings differed from hepatitic cirrhosis. In two patients serial biopsies confirmed development of cirrhosis from centrilobular necrosis.
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PMID:Five patients with nonalcoholic diabetic cirrhosis. 46 92

Medical records of the Pima Indian population aged 0--24 yr were reviewed for a diagnosis of diabetes before initiation of glucose tolerance testing. None of 1556 subjects below age 15, but 6 of 657 aged 15--24, had a previous diagnosis. Of the six known diabetics, five had been treated with insulin and four had had ketoacidosis. Subsequently, plasma glucose levels were determined after a 75-g oral carbohydrate load in 1712 subjects aged 5--24 yr, which is about 78% of the eligible population. Previously diagnosed diabetes and asymptomatic hyperglycemia were more frequent in subjects 15--24 yr old than were reported in other populations. Glucose intolerance in young Pimas was associated with obesity. In Pima offspring, the presence of diabetes in both parents was related to glucose tolerance in those above but not below the age of 15 yr. Both asymptomatic hyperglycemia and insulin-requiring diabetes occurred frequently in young Pimas, suggesting that these syndromes represent the clinical spectrum of a single disease in the Pima Indian.
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PMID:High prevalence of diabetes in young Pima Indians: evidence of phenotypic variation in a genetically isolated population. 47 85

Obese (ob/ob) and diabetes (db/db) mice are genetic mutants that have been shown to have altered levels of central catecholamines as well as syndromes of obesity, hyperphagia, and hyperglycemia. Because of catecholamines, and particularly norepinephrine (NE), are implicated in the control of feeding, levels of central catecholamines were experimentally reduced in ob/ob and db/db mice to investigate the role of the catecholamines in these cases of spontaneously occurring obesity. Lesions produced by 6-hydroxydopamine (6-OHDA) were used to produce large depletions of NE and dopamine (DA) in both ob/ob and db/db mice and in lean control mice of the same background strains. In the db/db but not the ob/ob, central catecholamine depletion was accompanied by a significant and persistent weight loss and by a reduction in plasma glucose levels when compared with vehicle-infused controls. Treatment with the NE uptake blocker desmethylimipramine (DMI) prior to 6-OHDA infusions attenuated NE but not DA depletion. Diabetes mice that received DMI pretreatment showed a weight loss and decrease in plasma glucose proportional to the amount of NE depletion. Lean mice that received the 6-OHDA treatments showed only a transient weight loss and no significant change in blood glucose. It is concluded that abnormalities in central noradrenergic systems may account for part of the obesity syndrome observed in the diabetes mouse.
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PMID:Differential effects on body weight of central 6-hydroxydopamine lesions in obese (ob/ob) and diabetes (db/db) mice. 52 20

Hyperglycemic obese and hyperinsulinemic mice of DBM strain develop a diabetic syndrome which can be compared to human maturity onset diabetes. In this study 6 to 49 weeks old female mice were used. Hyperglycemia and concomitant obesity were observed at 9 weeks. Plasma immunoreactive insulin (IRI) was maximum at 15--20 weeks, then decreased progressively with broad individual variations. Metformin, administered at 200 mg/kg per os, ineffective dosage in normal mice, showed a strong hypoglycemic effect in younger mice (11--18 weeks) with a plasma IRI decrease and no blood lactate and liver glycogen alteration. Plasma metformin concentration curve showed an exponential elimination fitted to a one compartment model with a plasma half-life of 2.7 hours. Metformin-induced hypoglycemia was lower in older mice (23--29 weeks) and corroborated their lower initial plasma IRI. All these results are in accordance with those reported in man and show that DBM mice provide a suitable model for a better understanding of antidiabetic drugs effects.
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PMID:DBM mice as a pharmacological model of maturity onset diabetes. Studies with metformin. 52 68

The natural history of patients with glucose intolerance was observed in 334 patients during a period of 18 years. Glucose tolerance testing (100 g orally) was characterized by measurement of induced insulin secretion. Diabetic complications of retinopathy, sensory neuropathy, and renal disease developed only in the group of patients in whom the induced serum insulin peak fell below 60 mu U/ml. Preservation of an insulin secretory reserve that permitted serum insulin peaks of 60 muU/ml or greater was not associated with development of these complications or symptoms of insulin deficiency despite the presence of an equal degree of fasting hyperglycemia and glucose intolerance. A critical amount of insulin secretory reserve distinguishes between two qualitatively distinct clinical syndromes: true diabetes mellitus (the development of signs and symptoms of insulin deficiency) and the syndrome of pure resistance to insulin (signs and symptoms of hyperglycemia in the setting of adequate or excessive insulin secretion, frequently with obesity, but without diabetic complication).
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PMID:Insulin secretion in the diagnosis of adult-onset diabetes mellitus. 67 27


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