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

Hypoglycaemic and growth hormone responses were studied at different steady-state plasma insulin concentrations during a graded infusion of monocomponent human insulin. The control group consisted of ten volunteer subjects. The other groups studied included women taking oral contraceptives and patients with obesity, thyrotoxicosis, myxoedema, acromegaly, diabetes mellitus (moderate and severe) and liver disease. The hypoglycaemic response was measured in two ways: (i) the percentage reduction in plasma glucose below basal, and (ii) the rate of fall of plasma glucose (Kg-%/min). Insulin sensitivity was greatest in the normal subjects and in the other groups decreased in the order thyrotoxicosis greater than oral contraceptive greater than obesity greater than myxoedema greater than acromegaly greater than liver disease. Insulin sensitivity was difficult to assess in the diabetic patients because basal plasma glucose concentrations were elevated. At any given insulin concentration, the diabetics metabolized approximately the same amount of glucose as the normal subjects but the fact that this rate of glucose turnover occurred at higher plasma glucose concentrations probably indicated insulin resistance. Within each group Kg at each dose level of insulin correlated with the steady state plasma insulin concentration during the same infusion period. Diminishing sensitivity to insulin was reflected in an increasing fasting plasma insulin and insulin/glucose ratio except in patients with diabetes. GH responses to insulin infusion in normal subjects reflected the pattern of fall of plasma glucose. In the diabetic patients GH secretion appeared to be related to the infusion of insulin and occurred before plasma glucose had fallen to hypoglycaemic levels. GH secretory patterns were within normal limits in women taking oral contraceptives and in seven of eleven patients with liver disease but were impaired in three of seven patients with thyrotoxicosis and four of five patients with myxoedema. Four obese patients had a markedly delayed but eventually normal GH response.
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PMID:Metabolic responses to monocomponent human insulin infusions in normal subjects and patients with liver and endocrine disease. 110 16

The growth and metabolic activity of cultured cells derived from human adipose tissue (CAT cells) were studied and compared to cultured skin fibroblasts. The morphological appearance of the CAT cells was distinctly different from that of fibroblasts. The growth rate of CAT cells as measured by 3H-thymidine incorporation was much slower than the fibroblast growth rate. Cultured CAT cells synthesized significantly 14C-glucose, while fibroblast cultures had a higher metabolic rate as measured by CO2 production. Insulin stimulated 3H-thymidine incorporation in both CAT and fibroblast cultures. The CAT cells did not show a consistent insulin response of lipid or CO2 production, but this may be a reflection of donor age or nutritional status. Even though the CAT cell may be a type of stromal cell peculiar to adipose tissue rather than a preadipocyte or adipocyte, it may prove useful in studies of human obesity.
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PMID:Observatons on the growth and metabolic functions of cultured cells derived from human adipose tissue. 115 32

Insulin-carbohydrate relationships were investigated in four groups of young rats fed low protein diets differing in carbohydrate and fat contents: (1) a diet in which the nonprotein energy was provided by fatty acids (FA); (2) a similar diet in which the fatty acids were substituted by neutral fat (NF); (3) FA diet supplemented with glycerol (FA-Glyc); and (4) a carbohydrate-rich diet (HC). Control rats were fed a stock diet. Rats fed the FA diet lost weight, were hypoglycemic and hypoinsulinemic in the fed state and normoglycemic and normoinsulinemic in the fasted state, and had an impaired glucose tolerance and hyperinsulinemia after a glucose load. Liver and muscle glycogen were low in fed rats. Fasting increased glycogen in liver and decreased glycogen in muscle. NF animals gained weight, were hypoglycemic in both fed and fasted states, and their plasma glucose level after an oral glucose load was almost normal. Plasma insulin/glucose ratio, both in fed and fasted states and after a glucose load indicated hyperinsulinism, which was accompanied by obesity. Muscle and liver glycogen were low in fed animals and did not change after a fast. Supplementation of the FA diet with glycerol (FA-Glyc) abolished weight loss and fasting hyperglycemia and normalized plasma glucose and insulin response to a glucose load. Rats fed the HC diet had an improved glucose tolerance and an increased sensitivity to insulin. Liver glycogen was high in the fed state and normal in the fasted state, whereas muscle glycogen was normal in both nutritional states.
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PMID:Effects of carbohydrate-free diets on the insulin-carbohydrate relationships in rats. 115 29

The action of insulin (0.1 U/ml) on the metabolism of human intestinal smooth muscle was studied in vitro. The experiments were performed on the muscle layer of human jujunum obtained from patients undergoing intestinal shunt operations because of obesity. Insulin significantly increased glucose uptake, glycogen content, the membrane transport of alpha-amino-isobutyric acid (AIB), the incorporation of leucine into protein and tended to increase the membrane transport of the nonutilizable model monosaccharide 3-0-methylglucose. The effects of insulin were moderate and appeared after incubation times of 120 to 180 min.
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PMID:Effect of insulin on human intestinal smooth muscle. 118 19

Adipose tissue from twelve normal-weight and ten obese subjects on weight-maintaining diets and nine obese subjects on hypocaloric diets was removed at surgery and incubated in vitro. Basal glucose oxidation correlated significantly (r = 0.68, p less than 0.005) with fat-cell diameter in subjects on weight-maintaining diets. This relationship was significantly altered (p less than 0.02) in subjects on calorie-restricted diets. In tissue from subjects on weight-maintaining diets, physiologic concentrations of insulin (25 muU./ml.) significantly increased glucose incorporation into carbon dioxide (p less than 0.005) and glycogen (p less than 0.001). Maximum insulin-stimulated glucose oxidation (increase over basal) was significantly enhanced (p less than 0.05) in tissue from obese subjects, whereas insulin-mediated glucose incorporation into glycogen was similar in controls and obese subjects on weight-maintaining diets. Insulin-stimulated glucose oxidation was imparied in tissue from subjects on hypocaloric diets although fat-cell diameter was similar to those of obese subjects on weight-maintaining diets. The effect of insulin on glucose incorporation into glycogen in isolated adipocytes was also studied. There was no correlation between insulin-stimulated glycogen synthesis and cell diameter. When cells from the same individual were separated into small and large adipocytes by differential flotation, the insulin effect was similar whether expressed as absolute or per cent increase over basal. These results indicate that in vitro glucose oxidation by adipose tissue, in both the absence and the presence of insulin, is largely determined by dietary factors. This may also be true for insulin-stimulated glycogen synthesis. No evidence is provided for the concept that the enlarged human fat cell of obesity is insensitive to insulin in vitro.
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PMID:Insulin sensitivity of the large human adipocyte in vitro. 119 13

Insulin, proinsulin and glucagon extracted from lean rat pancreases were studied in radioimmunoassay, radioreceptorassay and bioassay systems. Extracted insulin behaved identically to a rat insulin used as a reference standard in radioimmunoassay. On the basis of its immunoreactivity, extracted insulin was slightly less potent (about 70%) than the rat standard insulin in competing with the binding of 125I-insulin to rat liver membranes (radioreceptorassay) and in stimulating glucose oxidation by rat fat cells (bioassay). Extracted glucagon and a pork glucagon used as a reference standard were indistinguishable in two radioimmunoassay systems for glucagon, in competing with the binding of 125I-glucagon to rat liver membranes (radioreceptorassay) and in stimulating adenylate cyclase in rat liver membranes (bioassay). Genetically obese rats (Zucker, "fatty") were compared to their lean littermates with respect to insulin, proinsulin and glucagon extracted from their pancreases. Proinsulin represented the same proportion of total immunoreactive insulin in both types of rats. In the radioimmunoassays, the radioreceptorassays and the bioassays, insulin, proinsulin and glucagon from obese rats were indistinguishable from insulin, proinsulin and glucagon from lean rats. It is concluded that the pancreatic hormones of obese ("fatty") rats possess the same immunoreactivity and biological potency as those of nonobese rats. This excludes the possibility that some alteration in the biological properties of pancreas insulin and/or glucagon of fatty rats could explain the metabolic abnormalities observed in this type of obesity.
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PMID:Glucagon and insulin from lean rats and genetically obese fatty rats: studies by radioimmunoassay, radioreceptorassay and bioassay. 120 22

Lean mice were made obese by feeding, ad libitum, a high-lard diet. They showed an increased fat cell size and number which were maintained when this diet was replaced by the control high-carbohydrate diet for 10 weeks. Obese fed mice showed normal glucose and insulin serum levels, but insulinaemia was elevated after an overnight fast. The insulinaemic response after intraperitoneal injection of glucose was insignificant. Thus hyperinsulinism is not a prerequisite for the development of obesity. High-fat diet influenced, in vitro, glucose metabolism of adipose tissue, liver and muscle: basal lipogenesis was markedly reduced in adipose tissue and liver, and glucose oxidation was decreased in muscle. Insulin sensitivity was reduced by increased fat cell size. De novo formation of fatty acids in liver and adipose tissue did not contribute to the development of obesity. The increased lipoprotein lipase activity of the large fat cells suggested that obesity resulted from a direct storage of dietary fatty acids esterified by glycerol formed from circulating glucose.
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PMID:Metabolism of the mouse made obese by a high-fat diet. 123 69

The relationship between arterial blood pressure and clinically apparent diabetes mellitus was examined by measuring blood pressure, under standardised conditions, in 735 ambulant diabetic patients attending St. Mary's and King's College Hospital, London. Other biometric, clinical and family data were also systematically collected. A large proportion of first degree relatives of the diabetics and a control group of first degree relatives of non-diabetics were also seen and examined; they were also tested for the presence of unsuspected diabetes. Blood pressure in diabetics was evaluated in two ways. Mean pressures (systolic and diastolic) were calculated by age and sex and compared with similar data from two British non-diabetic populations. In addition, age and sex adjusted blood pressure "scores" were derived for each of the diabetic propositi and for the relatives by calculating the degree to which their pressures deviated from the mean of a corresponding age/sex group of non-diabetics. These deviations were then made comparable by standardising them for the systematic change in variance with age and sex. Using both "raw pressures" and "adjusted scores" the influence of age, sex, obesity, arm girth, response to diagnosis and ethnic, obstetric and anamnestic features were examined. Analysis of the influence of various characteristics of the diabetic state on blood pressure was made; this included mode of presentation, known duration; insulin dose and degree of metabolic control. Finally the relationship of blood pressure levels to the long-term sequels of diabetes was analysed with special reference to renal disease, eye changes, neuropathy and arterial disease. No systematic difference between arterial blood pressure in diabetics and a suitable control population was detected. Younger patients, females more than males, tended to have somewhat higher mean diastolic pressures but these were balanced by rather lower mean pressures in older diabetics. There was evidence of raised pressure levels at the time of diagnosis of diabetes, particularly in older patients, which "settled" with time for reasons which were not clear. The relationship of arterial pressure with adiposity was comparable to that in non-diabetics. After allowance for age and sex, blood pressures and scores were not related to the mode of onset of the diabetes. In the youngest onset group, however, known duration of diabetes appeared to correlate positively with arterial pressure in excess of the effect of age. Insulin dose and metabolic characteristics of the diabetes showed little clear association with arterial pressure but, as expected, patients with evidence of renal disease had higher mean pressures. However, cause-effect relationship between raised pressure and renal disease in diabetics may operate in both directions. Some elements of retinopathy were positively correlated with blood pressure; others were not. The role of co-existing renal disease in determining this association was examined...
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PMID:Arterial pressure in clinically apparent diabetics. 123 79

Obese-hyperglycemic (ob/ob) mice have the interesting feature of being hyperinsulinemic, thus having some characteristics in common with human maturity-onset diabetics. As the cause of hyperinsulinemia in these mice is not established, and as the liver is known to play a role in determining the amount of hormone that reaches the periphery, it was hypothesized that an anomaly in the hepatic handling of insulin might prevail in obese-hyperglycemic mice. Immunoreactive insulin was therefore measured in the perfusate before and after a single passage through perfused livers of lean and ob/ob mice, permitting. It was found that the removal of insulin by livers of lean mice increased with increasing concentrations of the hormone in the portal vein. The removal process had a limited capacity, however, and as a consequence the percentage of hormone removed by the liver actually decreased when portal insulin concentrations increased. Insulin removal by livers of ob/ob mice had qualitatively the same characteristics but was considerably less efficient than in normal livers. Due to this, more insulin was found in the perfusate leaving the liver of ob/9b mice than in that of controls, at any insulin concentration tested. These observations suggest that in obese-hyperglycemic mice more of the hormone may reach the periphery and thus contribute to hyperinsulinemia. The present study further suggests that the anomaly of insulin removal observed in perfused livers of ob/ob mice might be secondary to hyperinsulinemia, since it was partly corrected upon artificially decreasing the circulating levels of insulin (e.g. via a fast, anti-insulin serum, or streptozotocin treatment) before perfusion. The characteristics of hepatic insulin removal reported in this study, as well as the differences observed between livers of lean and ob/ob mice, may reflect changes in membrane insulin receptors and/or in processes responsible for the degradation of the horomone.
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PMID:An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice. 126 59

The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose.
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PMID:Management of non-insulin-dependent diabetes mellitus. 128 May 75


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