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Biomedical subjects

R Lauro

Publications and source records attributed to R Lauro.

At least 73 records · Page 4Linked to original sources

Changes in insulin receptors during oral contraception.

Combined estrogen/progestagen oral contraceptives (OC) have been reported to be associated with a deterioration of glucose tolerance and a decrease in insulin sensitivity; thus, since it has been suggested that steroids affect insulin receptor properties, the influence of OC on insulin receptors was investigated. The study groups were composed of nine normal menstruating women (controls), nine pill users, and two healthy women on OC for the first time. Insulin receptors on monocytes were evaluated at 7-day intervals during the 28 days between menses. Insulin receptor concentration and/or affinity did not show any variation in pill users during the test period and did not differ from values observed in controls in the luteal phase; consequently, the insulin receptor concentration in pill users is lower than that during the follicular phase or in men. The physiological variation of insulin receptor concentration and the increase of receptor affinity in the midfollicular phase, which characterize the normal menstrual cycle, are therefore abolished by OC. This effect occurs rapidly because it was also evident in the two women on OC for the first time. No difference was observed in fasting blood glucose and serum immunoreactive insulin concentrations between control subjects and pill users. The present data appear to confirm that sex steroids affect the insulin receptor and lend further support to the concept that caution must be used in clinical studies of insulin receptors when women are included. In addition, the results suggest that insulin receptors may play a role in the glucose intolerance and insulin insensitivity which have been described in pill users.

Adult↗

[In vivo effects of conjugated estrogens on the insulin receptor and on glucose binding in isolated adipocytes of male rats].

Studies have been carried out with labeled substrates on isolated adipocytes of male rats injected with sulpho-conjugated estrogens. Three days treatment did not affect insulin receptor concentration or affinity in the cells. Conversely glucose uptake is reduced in the absence of insulin, or by reduced responsiveness in the presence of it. After ten days treatment, insulin binding impaired on account of reduced receptor concentration, whereas glucose uptake was normal in the absence of insulin, increased at low and decreased at high insulin concentration, on account of both decreased responsiveness and increased sensibility to insulin. Thus it is suggested that estrogens acts on glucose uptake prior to act on the insulin receptor in the adipocytes.

Adipose Tissue↗

Binding properties of the insulin receptor of human placenta under different conditions of incubation.

The effect of incubation temperature and media on insulin receptor has been investigated employing membranes (4,000 x g pellet; particulate receptor) and solubilized material (solubilized receptor) from normal human placenta. Particulate receptor concentration (Ro) and affinity (Ke) were seen to be affected by buffer employed in binding experiments, both at 24 degrees C as well as at 4 degrees C; solubilized receptor affinity, on the other hand, is affected by buffer at 24 degrees C but not at 4 degrees C and receptor concentration does not vary at either temperature. Solubilization induced an increase in receptor affinity or in receptor concentration depending upon the buffer used in binding experiments. Insulin binding increases at the lowest incubation temperature; this phenomenon is due entirely to the greater receptor affinity on both particulate and solubilized receptor. From these data it appears that buffers induce variations in binding properties of the human placenta insulin receptor, thus, at ths present state of our knowledge, no definite conclusions can be drawn on the effect of procedures, such as solubilization, on human placenta insulin receptor affinity and/or concentration.

Buffers↗

Effects of prazosin on the cAMP system in the spontaneously hypertensive rat (SHR) aorta.

3',5'-adenosine monophosphate (cAMP), adenylate cyclase and cAMP-phosphodiesterase (PDE) activity were measured in aorta homogenates from normal and spontaneously hypertensive rats (SHR) during treatment with prazosin, an antihypertensive drug. cAMP levels were lower in SHR than in normal rats. In SHR prazosin treatment induced marked inhibition of PDE activity thus causing an increase in cAMP levels; adenylate cyclase activity remained unaffected. This effect was only present for the first 32 days of drug administration.

3',5'-Cyclic-AMP Phosphodiesterases↗

Insulin antibodies prevent insulin-receptor interactions.

The study was carried out to investigate whether insulin bound to antibody is able to bind the insulin receptor of target tissues. Three specific rabbit anti-insulin sera as well as sera from eight diabetic patients with insulin antibodies were incubated, free of insulin, with labelled insulin for 48 h at 4 degrees C; following incubation labelled insulin was employed in binding experiments on monocytes, erythrocytes and placenta membranes. Using rabbit sera, receptor binding was absent when insulin was totally combined with antibody, and appeared in increasing amounts as the percentage of free insulin increased to reach a maximum when no insulin was combined with antibody. The same experiment using sera from diabetic patients showed a close negative relationship (r = 0.95) between the amount of insulin bound to the antibody and the amount bound to receptors. The influence of the insulin-antibody complex on the insulin receptor interaction was evaluated by exposing the insulin-antibody complex to the receptor in pH, temperature and competition-inhibition curve experiments. The complex had no effect on receptor affinity or on the pH and temperature relationship influence with insulin-receptor interaction. The findings suggest that insulin resistance in the presence of insulin antibodies is due only to an alteration occurring before the interaction of insulin with its receptor, and demonstrate that the insulin-antibody complex does not influence the insulin receptor interaction.

Binding, Competitive↗

Differences in insulin receptors between men and menstruating women and influence of sex hormones on insulin binding during the menstrual cycle.

Specific binding of [125I]insulin to circulating monocytes and erythrocytes from nine normal menstruating women and nine normal men was determined during a 28-day period (one sample every 7 days). In women, insulin binding was higher to both monocytes (P less than 0.001) and erythrocytes (P less than 0.02) in the follicular phase than in the luteal phase. In men, insulin binding to monocytes was similar to the follicular phase values for women; however, insulin binding to erythrocytes from men showed higher values than insulin binding to erythrocytes from women in both the follicular (P less than 0.001) and luteal (P less than 0.001) phases. These differences were due primarily to changes in receptor concentration rather than receptor affinity. An inverse relationship was found between insulin binding to monocytes and levels of 17 beta-estradiol, progesterone, and 17 alpha-hydroxyprogesterone; this relationship was not observed in insulin binding to erythrocytes. The present data, therefore, suggest that sex hormones may play a role in the control of insulin receptors. Furthermore, it appears that other factors exist during the follicular phase that lower insulin binding to erythrocyte insulin receptors. If insulin receptors on circulating cells reflect the behavior of the main insulin target tissues, the present data might in part explain the reduction in glucose tolerance reported by various authors in the second half of the menstrual cycle.

Adult↗

Effect of dexamethasone and cortisone on insulin receptors in normal human male.

Results of a recent study suggested that depending upon the glucocorticoid or the model used, opposite changes occur in insulin binding; in fact, the increase in insulin receptor number on monocytes after prednisone ingestion in man appears to contrast with previous reports in animals in which a decrease was shown after dexamethasone. To establish whether this apparent discrepancy depends upon the model used in human studies (i.e. monocytes), the effect of dexamethasone and corticone intake on normal men was evaluated. A significant decrease was observed in insulin binding on circulating monocytes 24, 48, and 72 h after both steroids, mainly due to reduced receptor affinity. Furthermore, steroid treatment increased insulinemia which did not appear to be related to insulin binding. These data are in agreement with results in animal studies and appear to suggest that previous data on prednisone do not depend upon the model used (i.e. monocytes) but upon the hormone itself, thus indicating that glucocorticoids, depending upon their chemical structure, may produce opposite changes in membrane insulin binding sites. Furthermore, since dexamethasone and cortisone affect plasma insulin levels in the same fashion as previously reported with prednisone, it is suggested that the variation in insulin binding observed after glucocorticoid treatment is not due to variations in insulinemia.

Cortisone↗

Insulin receptors on monocytes and erythrocytes from obese patients.

Insulin receptors were studied in monocytes and erythrocytes [red blood cells (RBC)] isolated from 15 normal and 15 nondiabetic obese outpatients on an unrestricted diet. Insulin binding on both monocytes (P < 0.001) and RBC (P < 0.01) was higher in normal than in obese subjects due to different receptor concentrations. In some obese patients, binding to monocytes was decreased, while binding to RBC was normal. These data demonstrate that obese out-patients on an unrestricted diet have a reduced number of insulin receptors. It is suggested that interpretation of insulin binding based upon RBC should be used with caution, since a discrepancy exists in some subjects in the results obtained with these cells and monocytes.

Adult↗

Erythrocyte insulin receptors in non-insulin-dependent diabetes mellitus.

Insulin binding was studied on circulating erythrocytes isolated from 12 normal and 12 untreated, adult, nonobese, nonketotic, non-insulin-dependent diabetic subjects. Insulin binding in normal subjects was higher than in diabetics (P less than 0.01); binding variation was caused mainly by a reduction in insulin receptor concentration. Insulin binding was inversely correlated with fasting serum insulin levels (R = 0.49; P less than 0.01). The close agreement between the present data and previous data on other cell populations suggests that isolated erythrocytes may be a useful tool in clinical investigations on the human insulin receptor.

Diabetes Mellitus↗