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ABSTRACT: In the present study the effect of long-term fasting (6 days) on obese (ob) gene expression was examined in nine severely obese females of 34 +/- 3 years and with a body mass index of 46.4 +/- 2.3 kg/m2. Six days of fasting induced a significant weight loss (126.8 +/- 5.3 vs 120.5 +/- 5.1 kg, P < 0.0001). Insulin-stimulated glucose uptake (hyperinsulinemic, euglycemic clamp, insulin infusion rate 1.5 mU/kg per min) was markedly reduced following fasting (M-value 5.96 +/- 0.74 vs 2.79 +/- 0.23 mg/kg per min, P < 0.0001). Ob mRNA/beta-actin concentration in fat biopsies from abdominal subcutaneous adipose tissue was unchanged after 6 days of fasting (1.50 +/- 0.40 vs 1.47 +/- 0.36 arbitrary units, not significant), whereas serum leptin levels decreased significantly from 53.8 +/- 4.7 to 30.7 +/- 2.0 ng/ml (P < 0.0001) during the same period. No significant correlations were found between insulin-stimulated glucose uptake and serum leptin concentration, either prior to the fast or after the fast. Serum leptin levels were unchanged by hyperinsulinemia for 3 h during the clamp prior to the fast, while hyperinsulinemia for 3 h after 6 days of fasting increased serum leptin by 25% (P < 0.01). In conclusion, 6 days of fasting reduced serum leptin by about 40%. In contrast, ob mRNA in abdominal subcutaneous adipose tissue was unchanged. Furthermore, after 6 days of fasting insulin was able to increase the serum level of leptin significantly, indicating that the effect of insulin on the level of leptin is dependent on the nutritional state.
European Journal of Endocrinology 09/1997; 137(3):229-33. · 3.42 Impact Factor
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E Hjøllund
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ABSTRACT: Since the beginning of the seventies, studies of the cellular mechanisms behind insulin resistance in man have included studies of insulin receptor binding and insulin action in isolated cells. In the first studies, only measurements of insulin binding to circulating blood cells (mononuclear cells and erythrocytes) were possible. In these studies it was thus necessary to anticipate that insulin binding to these cells was representative for binding to target cells for insulin (adipocytes, hepatocytes, muscle cells). Later, studies of the human adipocyte became available. In the isolated human adipocyte it was possible to measure both insulin binding and the action of insulin on glucose transport and on the intracellular glucose processing. Immediately, it was observed that receptor binding to the different cell types was not always comparable. Moreover, the relationship between fat cell insulin binding and action was not always straightforward. Because fat tissue is only responsible for a small fraction of total glucose uptake, it is not possible to know whether changes in insulin binding and action in this tissue is representative for changes in the total organism. In the present review these problems have been elucidated by studies of patients with insulin-dependent and non-insulin-dependent diabetes mellitus. In chapter one, the methods used in the clinical studies are reviewed. The precision (intraassay variability) and reproducibility (intraperson variability) has been measured for all insulin receptor assays. It was found that the earlier used assay for mononuclear cells was improved by using a pure monocyte assay, because precision as well as reproducibility was improved. On the other hand, these values were considerably poorer than those found for the other cell types. The precision was 0.09, 0.04, and 0.04 for monocytes, erythrocytes and adipocytes, respectively. The reproducibility was 0.19, 0.06 and 0.11. In order to be able to measure comparability between insulin binding to the above mentioned cell types and hepatocytes, methods for measurement of insulin binding to these cell types from swine have been developed. These studies showed that insulin binding to swine cells have many similarities to that of human cells whereas several dissimilarities were seen between insulin binding to rat and human cells. Thus, it is surmised that swine cells are more suitable than rat cells concerning insulin receptor binding and action studies.(ABSTRACT TRUNCATED AT 400 WORDS)
Danish medical bulletin 07/1991; 38(3):252-70. · 0.75 Impact Factor
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ABSTRACT: We have described the receptor binding of A14-labelled [125I]insulin to viable adipocytes, hepatocytes, monocytes and erythrocytes from the pig. For all cell types the binding was of high affinity, specific for insulin, the non-specific binding low and degradation of insulin in the medium was minimal. At 24 degrees C, steady state insulin binding was achieved in all four cell types. At 37 degrees C, steady state insulin binding could be measured to adipocytes and hepatocytes. Specific insulin binding levels and receptor affinity for blood and fat cells from the pig are comparable to that in human cells, whereas differences, especially according to affinity, exist between pig and rat cell insulin receptor binding. It is therefore concluded that the pig is a more suitable model for studies of insulin binding in man than rodents. Finally, no correlations between the individual binding levels to the different cell types were observed. Hence, measurement of insulin binding to the easier available blood cells cannot replace studies of insulin binding to target cells of insulin.
Acta endocrinologica 06/1988; 118(1):59-67.
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ABSTRACT: Uptake and metabolism of the physiologically labelled D-glucose (D-[U-14C]glucose) has been characterized in human adipocytes at several unlabelled D-glucose concentrations in the absence and presence of insulin. Following a 90 min incubation, about 80% of the intracellular radioactivity was incorporated into total lipids at tracer glucose concentration, as well as at higher glucose concentrations in basal and insulin-stimulated cells, whereas 20% was recovered as hydrophilic metabolites. The only 14C-labelled metabolite escaping the cells in detectable amounts was CO2, which accounted about 4%. At trace glucose concentrations (5 mumol/l), the rate of glucose uptake was linear with time. Comparative studies of initial glucose uptake after 10 s and tracer D-glucose conversion to total lipids after 90 min showed high coefficients of correlation between basal rates (r = 0.87), maximal response above basal level to insulin (r = 0.92) and insulin sensitivity (r = 0.78). Thus, under these conditions glucose transport is rate-limiting for net glucose uptake, and measurements over long time intervals of rates for total cell-associated radioactivity or lipogenesis may serve as reliable estimates of initial glucose influx rates. However, the conversion rate of tracer glucose to metabolites decreased progressively with the glucose concentration and with an apparent Km of about 0.2 mmol/l. The three metabolic pathways exhibited similar percentage decreases in their activities, suggesting that a common enzymatic step is rate-limiting. In comparison, the Km for initial D-glucose uptake rate was about 7 mmol/l. Hence, the capacity for total glucose metabolism comprised only a small fraction of the glucose transport capacity at medium glucose concentrations above tracer concentrations. Both basal, half-maximal and maximal insulin-stimulated rates of adipocyte glucose utilization were dependent on the glucose concentration. Thus, comparing lipogenesis at tracer and at 0.5 mmol/l medium glucose concentration, it was shown that the higher medium glucose concentration was associated with a 60% lowering of the basal rate, a 35% reduction in the percentage response above baseline to maximal insulin stimulation and a 4-fold increase in the insulin sensitivity. Obviously, these findings reflect some intracellular step(s) being rate-limiting at medium glucose levels above tracer values.
Biochimica et Biophysica Acta 02/1988; 937(1):93-102. · 4.66 Impact Factor
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ABSTRACT: To evaluate the relative contribution of insulin binding and postbinding defects of glucose utilization in peripheral tissue during normal and diabetic pregnancy, we have studied the in vitro insulin action of isolated adipocytes from eight nondiabetic pregnant women and nine pregnant women with insulin-dependent diabetes mellitus who were undergoing cesarian section. The pregnant women were compared with a matched group of normal nonpregnant women undergoing gynecologic surgery. Insulin binding to adipocytes measured at tracer insulin concentration was reduced by 45% (P less than 0.01) in normal pregnant women and by 30% (P less than 0.02) in pregnant women with diabetes. In contrast, no changes were found between the three groups in insulin binding to pure monocytes and erythrocytes. The glucose transport system in fat cells from both groups of pregnant women was characterized by impaired maximal (P less than 0.05) and half-maximal (P less than 0.05) response to insulin. When fat cell glucose metabolism was studied, pregnant diabetic women exhibited decreased basal lipogenesis (P less than 0.05) and decreased maximal responses of lipogenesis and glucose oxidation to insulin stimulation (P less than 0.05). Similar but less pronounced abnormalities were seen in glucose metabolism of adipocytes from nondiabetic pregnant women. In conclusion, both in late normal and diabetic pregnancy, insulin binding to adipocytes is significantly reduced and accompanied by decreased insulin sensitivity and reduced maximal insulin responsiveness of glucose transport and by impaired basal and maximally insulin-stimulated glucose metabolism.
Diabetes 06/1986; 35(5):598-603. · 8.29 Impact Factor
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ABSTRACT: Studies of the in vivo insulin action in conventionally treated Type 1 diabetic patients have shown insulin resistance, especially in poorly controlled patients. We reported previously on impaired basal and insulin-stimulated glucose utilization in adipocytes from Type 1 diabetic subjects. In this study we have examined whether a near-normalization of glycaemia and plasma levels of metabolites in Type 1 diabetic patients induced by continuous subcutaneous insulin infusion might reverse abnormalities of adipose tissue metabolism. 11 Type 1 diabetic subjects who had been treated conventionally with diet and insulin for 11 yr were studied before and after continuous subcutaneous insulin infusion for 6 months. In Type 1 diabetic patients before insulin pump treatment we found decreased adipocyte insulin binding (p less than 0.01), normal insulin binding to monocytes and erythrocytes, impaired insulin sensitivity of the adipocyte glucose transport (p = 0.02) and reduced basal and maximally insulin-stimulated rates of adipocyte glucose oxidation and lipogenesis (all p less than 0.05). After pump therapy for 6 months we found a further reduction of basal and maximal adipocyte glucose oxidation and lipogenesis (all p less than or equal to 0.05), whereas we found no significant changes of insulin receptor binding or insulin sensitivity of adipocyte glucose utilization. We conclude that continuous subcutaneous insulin infusion of Type 1 diabetic patients for 6 months aggravates the defects in basal (non-insulin-stimulated) and maximally insulin-stimulated glucose utilization of isolated adipocytes despite an optimization of glycaemic control and a near-normalization of plasma metabolites.
Diabetes research (Edinburgh, Scotland) 02/1986; 3(1):17-23.
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ABSTRACT: Previous studies have shown cellular insulin resistance in conventionally treated insulin-dependent diabetics. To determine whether insulin resistance is also present in insulin-dependent diabetics before the commencement of insulin therapy, we studied nine newly diagnosed untreated insulin-dependent diabetics and nine control subjects. Insulin binding to adipocytes, monocytes, and erythrocytes was normal in the diabetic individuals. Basal (noninsulin stimulated) glucose transport rate was normal, whereas the maximal insulin responsiveness of glucose transport was severely impaired (P less than 0.02). Insulin sensitivity as judged by left or rightward shifts in the insulin dose-response curves was unchanged. Moreover, the basal lipogenesis rate measured at a glucose concentration of 0.5 mmol/liter was decreased in the diabetics (P less than 0.05), and the maximal insulin responsiveness of lipogenesis was also reduced (P less than 0.05). We conclude that fat cells from untreated insulin-deficient diabetics are insulin resistant. The major defects are (1) reduced maximal insulin responsiveness of glucose transport and conversion to lipids that are postbinding abnormalities, and (2) reduced basal glucose conversion to lipids.
Journal of Clinical Investigation 01/1986; 76(6):2091-6. · 15.39 Impact Factor
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ABSTRACT: Insulin binding, glucose transport, and glucose metabolism were investigated in isolated adipocytes from 11 lean and 13 obese patients with non-insulin-dependent diabetes mellitus. Insulin binding at 15 degrees C was reduced by 35% (p less than 0.01) in both lean and obese diabetic patients, whereas insulin binding (or uptake) at 37 degrees C was similar in diabetic patients and healthy controls. In lean diabetic patients both non-insulin-mediated (basal) and maximally insulin-stimulated glucose transport and metabolism were significantly reduced (all p less than 0.01). The percentage responses to insulin were also markedly reduced (p less than 0.05, p less than 0.02). In obese diabetic patients basal glucose transport was reduced (p less than 0.01) but basal glucose metabolism was not. Insulin-stimulated glucose transport and metabolism were significantly reduced (p less than 0.01, p less than 0.05). The percentage responses were reduced compared to healthy controls (p less than 0.05, p less than 0.05) but higher than in lean diabetic patients (p less than 0.05). We conclude that adipocytes isolated from both lean and obese patients with non-insulin-dependent diabetes mellitus are characterized by severely depressed non-insulin-mediated and insulin-mediated glucose transport and depressed insulin-mediated glucose metabolism. The major defect seems to be a reduced maximal effect of insulin on glucose metabolism, suggesting post-binding and post-transport abnormalities.
Diabetic Medicine 12/1985; 2(6):468-73. · 2.90 Impact Factor
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ABSTRACT: It is now well established that longstanding human uremia is associated with impaired in vivo insulin action on glucose utilization of peripheral target tissues. In an attempt to define the cellular basis of the uremic insulin resistance we studied insulin action in adipocytes from eight patients with undialyzed chronic uremia and from eight matched healthy controls. (125I)-Insulin binding to fat cells from uremic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited half-maximal response was 422 +/- 95 pmoles/liter in uremic patients and 179 +/- 38 pmoles/liter in normal subjects (P less than 0.01). The noninsulin- and the maximal insulin-stimulated glucose transport of adipocytes from uremic patients with normal. (14C)-D-glucose conversion to total lipids was also measured in these cells in the absence and presence of various insulin concentrations. Similar to the findings in transport studies the lipogenesis of fat cells from uremic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmoles/liter in uremic patients and at 11 +/- 3 pmoles/liter in normal subjects, P less than 0.01) with unchanged noninsulin and maximal insulin-stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uremia may be accounted for primarily by postbinding defects localized to glucose transport and metabolism.
Kidney International 06/1985; 27(5):780-4. · 6.61 Impact Factor
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ABSTRACT: A three-step hyperinsulinemic euglycemic clamp was performed in 14 nondialyzed uremic and ten age-matched healthy subjects. Nine of the uremics were restudied for a mean of 42 days (range, 21 to 88 days) after initiation of dialysis therapy. Insulin was infused at the following three rates: 0.5 mU X kg-1 X min-1, 2.0 mU X kg-1 X min-1, and 4.0 mU X kg-1 X min-1. Each dose was given for 120 minutes. Glucose uptake during the last 30 minutes of each clamp were consistently lower in uremic patients pre-dialysis than in controls (2.3 +/- 0.3 v 6.6 +/- 0.8 mg X kg-1 X min, 7.8 +/- 0.6 v 13.2 +/- 1.1 mg X kg-1 X min-1 and 9.6 +/- 0.7 v 15.5 +/- 1.0 mg X kg-1 X min-1, all P less than 0.001). Serum insulin levels were similar in the two groups, and blood glucose values during steady state were maintained at 79 +/- 2.77 +/- 2, and 77 +/- 2 mg/100 mL in uremic subjects and at 72 +/- 3, 73 +/- 2, and 75 +/- 2 mg/100 mL in healthy subjects. The insulin levels required to elicit half-maximal biological response in uremics (82 +/- 5 microU/mL) were markedly higher than in controls (54 +/- 8 microU/mL, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism 06/1985; 34(5):465-73. · 2.66 Impact Factor
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ABSTRACT: The effects of prostaglandin E2 were studied on glucose metabolism (3-O-methylglucose transport, CO2 production and lipogenesis) in human adipocytes. Initially, the effects of endogenously produced adenosine and prostaglandins were indirectly demonstrated by using adenosine deaminase and indomethacin in the incubations. From these studies it was found that adenosine deaminase (5 micrograms/ml) had a pronounced effect on adipocyte glucose metabolism in vitro. In the basal (nonhormonal-stimulated) state, glucose transport, CO2 production and lipogenesis were inhibited by about 30% (P less than 0.05). Furthermore, adenosine deaminase significantly inhibited the isoproterenol- and insulin-stimulated CO2 production and lipogenesis (P less than 0.01). Indomethacin (50 microM) had a consistently inhibitory effect on the insulin-stimulated CO2 production (P less than 0.05), whereas indomethacin had no significant effects on basal or isoproterenol-stimulated glucose metabolism. In contrast to the relatively minor effect of endogenous prostaglandins, the addition of exogenous prostaglandin E2 significantly stimulated the glucose transport, glucose oxidation and lipogenesis in human adipocytes, especially in the presence of adenosine deaminase. Half-maximal stimulation was obtained at prostaglandin E2 concentrations of 2.2, 0.8 and 0.8 nM, respectively. The effect of prostaglandin E2 was specific, since the structurally related prostaglandin, prostaglandin F2 alpha, had practically no effect on glucose metabolism. The maximal effect of prostaglandin E2 (1 microM) on glucose metabolism was 30-35% of the maximal insulin (1 nM) effect. When insulin and prostaglandin E2 were added together, the effect of prostaglandin E2 on glucose metabolism was additive at all insulin concentrations tested.
Biochimica et Biophysica Acta 04/1985; 844(3):359-66. · 4.66 Impact Factor
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ABSTRACT: Glucose intolerance is a common concomitant of untreated chronic renal failure, but the effect of long-term treatment on the insulin resistance believed to be behind it is as yet not clarified. Peripheral tissue sensitivity to insulin was therefore examined in 7 dialyzed uraemic patients, 8 undialyzed uraemic and 8 matched healthy subjects using the hyperinsulinaemic euglycaemic clamp technique. The dialyzed subjects had been on maintenance haemodialysis for a mean of 4 yr (range, 3-131 months) and were studied both before and after a single random dialysis. The clamping was performed during 150 min using a glucose controlled insulin infusion system (Biostator). Insulin was infused at a rate of 2.0 mU/kg/min. Tissue sensitivity to insulin was expressed as glucose uptake (M) at steady state (90-150 min) over steady state serum insulin concentration (I). While M was significantly greater in healthy subjects (12.52 +/- 1.02 mg/kg/min, mean +/- 1 SEM) than in dialyzed uraemics (9.59 +/- 0.78 mg/kg/min and 9.36 +/- 0.70 mg/kg/min, both p less than 0.05), M/I was similar in chronically dialyzed patients (before and after dialysis: 0.098 +/- 0.017 mg/kg/min per microU/ml vs 0.104 +/- 0.020 mg/kg/min per microU/ml) and in controls (0.111 +/- 0.015 mg/kg/min per microU/ml; p greater than 0.20). In contrast M/I ratio of uraemic subjects who had never been dialyzed (0.062 +/- mg/kg/min per microU/ml) was significantly reduced (both p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes research (Edinburgh, Scotland) 04/1985; 2(2):57-63.
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ABSTRACT: In an attempt to define the cellular basis of the uraemic insulin resistance we studied insulin action in adipocytes from eight patients with undialysed chronic uraemia and from eight matched healthy controls. (125I)-insulin binding to fat cells from uraemic patients was normal. In contrast (14C)-D-glucose transport exhibited decreased sensitivity to insulin. The concentrations of insulin that elicited a half-maximal response were 422 +/- 95 pmol/L in uraemic patients and 179 +/- 38 pmol/L in normals (p less than 0.01). The non-insulin and the maximally insulin stimulated glucose transport of adipocytes from uraemic patients was normal. The lipogenesis of fat cells from uraemic patients had depressed sensitivity to insulin (half-maximal stimulation at 38 +/- 8 pmol/L in uraemic patients and at 11 +/- 3 pmol/L in normals, p less than 0.01) with unchanged non-insulin and maximally insulin stimulated lipogenesis. Taken together these results suggest that the insulin resistance of adipocytes from patients with chronic uraemia may be primarily accounted for by post-binding defects localised to glucose transport and metabolism.
Proceedings of the European Dialysis and Transplant Association - European Renal Association. European Dialysis and Transplant Association - European Renal Association. Congress 02/1985; 21:725-31.
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ABSTRACT: In vivo studies in noninsulin-dependent diabetic patients have indicated that sulphonylurea drugs have an extra-pancreatic effect. To further elucidate the mechanisms of this action, we studied the effect of glibenclamide on in vivo and in vitro cellular insulin receptor binding in normal subjects. Oral administration of glibenclamide in dose of 2.5 mg/day increased insulin binding to monocytes by 70% (P less than 0.001), in spite of increased postprandial serum insulin levels. This change in insulin receptor binding occurred in the absence of changes in diet or body weight. In contrast, glibenclamide had no stimulatory effect on in vivo insulin binding to erythrocytes. The in vitro studies with monocytes revealed a dose-related insulin receptor stimulatory effect of glibenclamide (P less than 0.05), with a maximal effect of 20% above basal level. These data indicate that glibenclamide increases the insulin-binding ability of monocytes but not of erythrocytes. As the monocyte is judged a better model for studying insulin receptors on target cells than the erythrocyte, this effect may be responsible, at least in part, for the extrapancreatic effect of sulphonylureas, which seem to be of major importance for their hypoglycemic effect in noninsulin-dependent diabetic patients.
Journal of Clinical Endocrinology & Metabolism 01/1984; 57(6):1257-62. · 6.50 Impact Factor
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ABSTRACT: Nine non-insulin-dependent diabetics were studied before and after 3 weeks on an isoenergetic high-fiber/high-starch/low-fat diet (alternative diet), and nine non-insulin-dependent diabetics were studied on their usual diet. In the group that ate the alternative diet, the intake of fiber and starch increased 120% and 53%, whereas fat intake decreased 31%. Diabetes control improved as demonstrated by decreased fasting plasma glucose (P less than 0.05) and 24-hour urinary glucose excretion (P less than 0.05). The in vivo insulin action increased (KIVITT increased, P less than 0.05) with no change in fasting serum insulin levels. In fat cells obtained from patients in the alternative-diet group, insulin receptor binding increased (P less than 0.05) after the change of diet. Insulin binding to purified monocytes (more than 95% monocytes) also increased (P less than 0.05), whereas no change was found in insulin binding to erythrocytes. When lipogenesis was studied at a tracer glucose concentration at which glucose transport seems to be rate limiting, insulin sensitivity increased (P less than 0.02). This is the predicted consequence of increased receptor binding. Moreover, when CO2 production and lipogenesis were studied at a higher glucose concentration, where steps beyond transport seem to be rate limiting for glucose metabolism, increased insulin sensitivity was also observed. In contrast, no change was found in maximal insulin responsiveness. Fat and blood cells from the patients who continued on their usual diet showed no changes of the mentioned quantities.(ABSTRACT TRUNCATED AT 250 WORDS)
Metabolism 12/1983; 32(11):1067-75. · 2.66 Impact Factor
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ABSTRACT: The present study was designed to determine the participation of a decreased insulin binding versus that of a post-binding defect in uraemic insulin resistance and to examine the possible effect of dialysis treatment. This was done by constructing an in vivo insulin dose-response curve using the euglycaemic clamp technique. We found that the maximal responsiveness to insulin was decreased in uraemic patients. Long-term dialysis treatment improved the maximum glucose metabolism significantly (7.7. +/- 0.7 mg/kg/min versus 10.7 +/- 0.6 mg/kg/min, p less than 0.01). On the contrary we found no clearcut alteration of the half-maximal insulin concentrations in relation to dialysis. In conclusion, this report indicates that the insulin resistance in uraemia is primarily due to post-binding defects, i.e. an impaired intracellular glucose metabolism or an abnormal glucose transport system.
Proceedings of the European Dialysis and Transplant Association. European Dialysis and Transplant Association 02/1983; 20:686-91.
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ABSTRACT: We have studied (125I)-insulin binding and insulin dose response relationships of (14C)-methylglucose transport conversion of (14C)-glucose to CO2 and total lipids, and lipolysis at 37 degrees C and pH 7.4 in adipocytes from obese patients before (n = 15) and after fasting for 10 days (n = 6). Studies of adipocytes from obese before fasting showed a significant reduction of insulin binding when expressed to cell surface area and rightward shifts of the insulin dose response curves (decreased insulin sensitivity) for glucose transport, glucose oxidation, lipogenesis and antilipolysis. The decreased insulin sensitivity of adipocytes from obese was most likely the functional consequence of the impaired insulin binding. Moreover, decreased maximal glucose transport capacities were present in rat cells from obese both in the basal and maximally insulin stimulated states. Similarly, the percentage response above basal level to maximal insulin stimulation of glucose oxidation and lipogenesis was impaired to these cells. The latter findings suggest post receptor defects localized both to the transport system per se and to intracellular mechanisms involved in the metabolism of glucose. Conversely, the post receptor pathways for the insulin induced antilipolysis was intact in fat cells from obese man. Studies after fasting showed an increase of adipocyte insulin binding accompanied by an increased sensitivity to the antilipolytic effect of insulin with unchanged maximal responsiveness. However, due to marked post receptor alterations, the insulin stimulated glucose utilization was severely blunted. Thus, the glucose transport system of adipocytes from all fasted subjects was totally unresponsive to insulin, while some of the fasted patients had a slight response of glucose oxidation and lipogenesis in the presence of insulin in maximally effective concentrations.
Metabolism 10/1982; 31(9):884-95. · 2.66 Impact Factor
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Diabetes 09/1982; 31(8 Pt 1):706-15. · 8.29 Impact Factor
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ABSTRACT: Insulin binding and action were studied in fat cells from the gluteal region of young healthy subjects. Fat cells from females were larger than those of males, had higher insulin receptor binding and higher rates of noninsulin-stimulated and maximally insulin-stimulated rates of methylglucose transport and glucose metabolism when these data were expressed per cell number. However, when insulin binding and insulin effects were expressed per cell surface, which may be physiologically more relevant, no sex differences were found in insulin binding and glucose transport, whereas noninsulin-stimulated and maximally insulin-stimulated glucose metabolism was still significantly increased in female fat cells. The latter indicates postreceptor differences in glucose metabolism between females and males. The insulin concentrations causing half-maximal responses (a measure of the sensitivity to insulin) of glucose transport, glucose metabolism and lipolysis were similar in fat cells from the two sexes, which is consistent with the comparable values of insulin receptor binding when adjusted to cell surface. Studies of rate-determining steps for the glucose utilization of human fat cells showed that glucose transport was not the rate-limiting step at physiological glucose concentrations. Moreover, at physiological glucose levels, glucose metabolism exhibited a decreased maximal insulin responsiveness and an increased insulin sensitivity when compared with glucose metabolism at low glucose concentrations at which glucose transport is rate limiting for the fat cell glucose utilization.
The American journal of physiology 09/1982; 243(2):E158-67.
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ABSTRACT: We have characterized the 24-h changes of insulin receptors on erythrocytes from patients with insulin-dependent diabetes of long duration. These diabetics were studied both in usual and poor metabolic control. Moreover, we have examined daytime changes of insulin receptors on monocytes from newly discovered diabetics. In both erythrocyte and monocyte studies, diabetics were compared to healthy controls. At insulin tracer concentration, insulin receptor binding to erythrocytes from diabetics in usual control and normal volunteers underwent a statistically significant diurnal variation with high binding values in the early morning, low daytime values with a nadir in the late afternoon, and a peak around midnight. Even diabetics in poor metabolic control due to insulin deprivation had preserved a similar 24-h rhythm of erythrocyte insulin receptors. Insulin receptor binding to monocytes at insulin tracer concentration declined significantly during the day both in newly discovered diabetics and in healthy controls. The mechanisms responsible for the acute phase changes of insulin-receptor binding are unknown, but the receptor changes seem related to the fed state. Moreover, analysis of the temporal interrelationship between erythrocyte insulin binding and plasma insulin concentration in diabetics during the 24-h period suggests that in these patients insulin may be one of the factors determining the rapid insulin receptor regulation.
The American journal of physiology 03/1982; 242(2):E127-36.
