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

Studies of 125I -insulin binding to erythrocytes (RBC) from 5 patients with Cushing's disease were performed in an attempt to evaluate the insulin resistance in this disease. Five obese, nondiabetic patients and six normal subjects served as controls. Insulin resistance was present in both the obese, nondiabetic subjects and in the patients with Cushing's disease. Patients with Cushing's disease showed insulin resistance out of proportion to obesity, and of greater severity than in the obese subjects. As in previous studies, the insulin resistance of the obese subjects could be at least partially ascribed to a reduced number of receptors. In contrast, in our patients with Cushing's disease, no physiologically significant changes in the parameters of insulin-receptor interaction could be demonstrated. This suggests that the RBC insulin receptor is not involved in this type of insulin resistance.
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PMID:Insulin resistance in Cushing's disease. Evaluation by studies of insulin binding to erythrocytes. 637 54

Type II, non-insulin-dependent, diabetes mellitus occurs worldwide, though with great variations in prevalence rates: the highest rates--about 30-35%--are reported for the Pima Indians and for the population of the island Nauru in the Pacific. The disease is to some extent inherited, but the mode of inheritance is unknown. Recent studies of the length polymorphism of the insulin gene, however, suggest that it may be possible to find a genetic marker for the disease. Obesity is common among type II diabetics, and the occurrence of the type II diabetes increases with age. One possible explanation is that both obesity and advanced age are associated with a decrease in insulin sensitivity. Insulin resistance is a common finding in type II diabetes; it has been demonstrated with several methods, including the euglycaemic insulin clamp technique. The role of insulin receptor and post-receptor defects in the pathogenesis of this insulin resistance is currently being studied with great interest. In addition to impairment of insulin sensitivity, there is a reduction in glucose-stimulated insulin secretion in individuals with type II diabetes. The primary defect of the disease, however, has yet to be established. Type II diabetes may well be a heterogeneous disorder with several different aetiologies; one argument for heterogeneity within the disease is the chlorpropamide alcohol flush reaction that can be demonstrated among about one third of type II diabetics. Further investigations of the pathogenesis of the disease are needed, and it is hoped that these will pave the way for the development of more specific therapy, and even prevention of the disease.
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PMID:The pathogenesis of type II diabetes mellitus. A brief survey. 638 83

By use of the glucose clamp sequential insulin infusion technique, we compared the dose-response characteristics of insulin-mediated glucose disposal in 17 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 13 age- and weight-matched nondiabetic volunteers. In terms of plasma insulin concentrations, the dose-response curve in the diabetics was shifted to the right (Km 156 +/- 28 vs. 58 +/- 4 microU/ml in nondiabetics, P less than 0.01) with a decreased maximum response (Vmax 320 +/- 22 vs. 405 +/- 10 mg X m-2 X min-1 in nondiabetics, P less than 0.01). Moreover, coupling between insulin receptor binding and activation of insulin effector units was defective in the diabetic subjects (half-maximally effective insulin receptor occupancy 184 +/- 11 vs. 145 +/- 12 pg in nondiabetics for monocytes, P less than 0.02, and 120 +/- 8 vs. 85 +/- 4 pg for erythrocytes in nondiabetics, P less than 0.01). The presence of defective coupling in itself could explain the abnormal insulin dose-response characteristics for glucose disposal in NIDDM and differentiates the insulin resistance of this condition from that of obesity in which coupling is normal.
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PMID:Abnormal coupling of insulin receptor binding in noninsulin-dependent diabetes. 638 57

The insulin binding properties and the molecular weights of the insulin receptor and its insulin binding subunit were studied in omental and subcutaneous adipocytes prepared from obese- and normal-weight subjects. Insulin binding by such adipocytes was decreased in obesity when the binding activity was expressed per unit of cell surface area. No significant difference from the lean controls was evident, however, when binding was calculated on a per cell basis, indicating that the total receptor content of the cells from the obese subjects was not altered. In addition, the normal difference in the receptor binding affinities previously reported between omental and subcutaneous cells from lean individuals was unaffected by the obese condition. Studies of the molecular weight of the non-reduced insulin receptor in fat cell membranes prepared from pieces of omental and subcutaneous fat demonstrated a major receptor species of 390-425K Mr. In contrast, adipocytes isolated by collagenase treatment of the fat had heterogeneous non-reduced receptor species of Mr 355K, 285K and small amounts of 427K and 182K. Although different non-reduced receptor species were evident depending on the adipocyte receptor preparation (e.g. isolated adipocytes or fat cell membranes), no differences were found between obese and lean controls or between subcutaneous and omental receptors when the appropriate comparisons were made. Upon sulphydryl reduction, all receptor preparations had a major binding subunit of 125K Mr. In conclusion, obesity is characterized by a dilution of the insulin receptor over the adipocyte cell surface in the absence of a change in total cellular content of receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Binding and molecular weight properties of the insulin receptor from omental and subcutaneous adipocytes in human obesity. 639 88

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

Hepatic glucose production and metabolic clearance rate of glucose were measured using (3-3H) glucose at steady state, basally and during two sequential 2 h insulin (25 and 40 mU . kg -1 . h -1)/glucose (2 and 3 mg. kg -1 . min -1) infusion periods. Eight diabetic subjects were studied before and after 1 week of twice daily insulin therapy; six control subjects matched for age, weight and degree of obesity were also studied. In the diabetic patients, pre-treatment hepatic glucose production was 20.0 +/- 2.2, 9.9 +/- 2.9, and 1.4 +/- 0.8 mu mol . kg -1 . min -1 respectively (+/- SEM) for each of the three periods, and fell significantly with treatment to 12.8 +/- 1.7, 4.0 +/- 1.5 and 1.9 +/- 1.0 mu mol . kg -1 . min -1. Hepatic glucose production in normal subjects was 13.2 +/- 0.6, 2.2 +/- 0.8 and less than 1 mu mol . kg -1 . min -1. The pre-treatment metabolic clearance rate in all diabetic studies with insulin levels greater than or equal to 30 mU/l was 1.10 +/- 0.14 ml . kg -1 . min -1 and remained virtually unchanged following insulin therapy; this was significantly lower than in the control subjects (6.83 +/- 1.02, p less than 0.001). Basal non-esterified fatty acid levels were higher (p less than 0.02) in the pre-treated diabetic patients compared to post-treated diabetic patients and control subjects. Non-esterified fatty acids in each group fell to similar levels during the insulin infusions, but the rate of fall was slower in the pre-treated diabetic patients. Insulin receptor binding to erythrocytes was normal in the diabetic subjects and unchanged by treatment. Therefore, following insulin treatment of uncontrolled Type 2 (non-insulin-dependent) diabetes, the initially increased basal hepatic glucose production, and decreased hepatic sensitivity, return towards normal. However, the glucose clearance remains low, despite good diabetic control, and appears to be a major factor in the continuing glucose intolerance. As insulin receptor binding is normal, the defect of glucose clearance in Type 2 diabetes appears compatible with a post-receptor defect of glucose metabolism.
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PMID:Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes. 675 16

The hyperinsulinemia of obese rodents has been associated with a reduced number of hepatic insulin receptors except in hepatocytes from fatty Zucker rats. We isolated liver plasma membranes from 10-11-wk-old lean and fatty Zucker rats, some of which were injected with streptozotocin 2--4 wk earlier. We have determined that although the number of hepatic insulin receptors is not reduced in young hyperinsulinemic fatty Zucker rats, the number of receptors can be increased when the hyperinsulinemia of the fatty rats is reduced by treatment with streptozotocin. In the fatty rats, this reduction in circulating insulin is accompanied by a reduction in plasma triglyceride concentration, consistent with a decreased stimulation of hepatic lipogenesis. Competitive binding curves for insulin were obtained with isolated liver plasma membranes and 125I-insulin. Analysis of these curves for affinity and number of receptors indicated that the number of insulin receptors was unchanged for the fatty control rats relative to the lean control rats but was increased in streptozotocin-treated animals. These data indicate that the regulation of hepatic insulin receptors is altered in the young fatty Zucker rat as characterized by a lack of downregulation of hepatic insulin receptors by hyperinsulinemia and an upregulation of hepatic insulin receptors at insulin concentrations higher than those found in lean rats. An altered state of hepatic insulin receptor regulation may be characteristic of developing obesity.
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PMID:Studies on the regulation of insulin binding by liver plasma membranes from Zucker fatty rats. 675 20

Two cases of insulin resistance are described, and recent developments in the pathogenesis and treatment of insulin resistance are reviewed. Both immune and nonimmune types of insulin resistance have been described. Immune resistance is related to the presence of circulating antibodies directed against exogenous insulin or the insulin receptor sites. Nonimmune resistance is associated with obesity, ketoacidosis, infection, or endocrinopathies. Treatment of insulin-resistant diabetics can include proper diet and weight control; use of insulin in large quantities; selection of less antigenic forms of insulin, such as pork, fish, or sulfated insulin; oral hypoglycemics such as tolbutamide; and immunosuppressive therapy with corticosteroids. The production of human insulin by recombinant DNA technology promises benefits to patients with high levels of antibodies directed against insulin from animal sources. True insulin resistance is a rare phenomenon, which must be documented adequately before vigorous treatment is considered.
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PMID:Insulin resistance: definition and treatment. 677 14

The New Zealand Obese (NZO) mouse was studied as a potential model for autoimmune diabetes. NZO mice develop obesity, glucose intolerance, and insulin resistance, and have low-titer IgM antibodies to the insulin receptor. It is shown that they have circulating antibodies to both native DNA and denatured, single-stranded DNA. The antibody levels are higher in females, and, up to 6 mo of age, are comparable to those found in the related NZB X NZW F1 (NZB/W) mouse, a model for systemic lupus erythematosus. After 6 mo of age the antibody levels in NZO mice fall toward normal, in contrast to the persistently elevated levels in NZB/W mice. NZB/W mice are known to succumb to immune complex-mediated proliferative glomerulonephritis before 1 yr of age, whereas NZO mice survive. NZO kidneys exhibit light microscopic features of both diabetic and lupus nephropathies: glomerular proliferation, mesangial deposits, mild basement membrane thickening, glomerulosclerosis, eosinophilic nodules in some glomeruli, occasional hyalinization of the glomerular arterioles, and healing arteriolar inflammation. These changes are associated with glomerular deposition of immunoglobulin, especially IgM, in a granular pattern on fluorescent staining. The NZO mouse, therefore, has evidence of a generalized immune disorder and provides a model for studying the relationship between autoimmunity, obesity, and diabetes.
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PMID:Diabetes is associated with autoimmunity in the New Zealand obese (NZO) mouse. 700 65

Effects of physical training on factors associated with diabetes mellitus and its increased risk for cardiovascular disease are reviewed. Plasma insulin levels are decreased by training particularly in obesity and glucose tolerance seems to be improved. Training leads also in general to diminished body fat, but this is not obligatory for the plasma insulin decrease. There are no changes in concentrations of amino acids growth hormone or catecholamines, which can explain the insulin decrease. Cortisol is decreased the days after an acute exercise as well as after training in parallel with the plasma insulin decrease. The cortisol decrease may lead to changes in insulin receptor density in tissues leading to increased insulin sensitivity. The insulin decrease seems to be due to both a decreased production (to about 2/3) and an increased clearance (to about 1/3). Physical training leads to a decrease in plasma triglycerides and to a decrease in blood pressure. All these effects of physical training seem to be beneficial in the treatment of diabetes mellitus.
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PMID:Metabolic effects of physical training. 701 Sep 7


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