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Biomedical subjects

R Gherzi

Publications and source records attributed to R Gherzi.

53 records · Page 3Linked to original sources
PubMed1987

Species specificity of insulin binding and insulin receptor protein tyrosine kinase activity.

The effect of monoclonal anti-insulin receptor antibody MA 10 on [125I]insulin binding and on insulin receptor protein tyrosine kinase activity was investigated in human and rat tissues. It was observed that MA 10 inhibits insulin binding to human, but not rat, tissues while inhibiting insulin-stimulated receptor autophosphorylation and protein tyrosine kinase activity in both human and rat tissues. These data suggest that MA 10 is directed against a region of the insulin receptor that is in between the insulin-binding domain and the beta-subunit and that in human, but not rat, tissues, this region is involved in insulin binding.

Adipose Tissue↗
PubMed1986

Insulin receptor autophosphorylation and kinase activity in streptozotocin diabetic rats. Effect of a short fast.

Insulin receptor associated kinase activity and its relationships with the insulin resistance of streptozotocin-induced diabetes were investigated in rats, using solubilized, partially purified insulin receptors from liver membranes. Insulin receptor kinase activity was measured by means of both autophosphorylation and phosphorylation of the exogenous substrate Glu4:Tyr1. Diabetes was associated with a 45% reduction in kinase activity, in the same number of insulin receptors, with no change in insulin binding affinity. To investigate the independent roles of hyperglycemia and hypoinsulinemia on the observed impairment of receptor kinase activity, diabetic rats were fasted for 24 h in order to normalize blood glucose levels only. After this short fast, no change in kinase activity, from the values measured in fed diabetic animals, was observed. Our findings suggest that streptozotocin diabetes is associated with a reduction of insulin receptor kinase activity, which a short fast is not able to reverse.

Animals↗
PubMed1986

Insulin-like growth factor I (IGF I) receptor autophosphorylation and kinase activity. Effect of a human polyclonal antibody (pIgG)

IGF I receptor is a tyrosine kinase capable of phosphorylating the receptor itself and other substrates. A high degree of homology does exist in tyrosine kinase domain among receptors for several polypeptide growth factor receptors and this enzymic activity has been indicated as a possible mediator of biological action. Nevertheless growth factor receptors possess peculiar specificities both in their functions and tissue distribution. A human polyclonal IgG (pIgG), previously characterized as anti insulin receptor antibody, able to inhibit insulin receptor kinase activity, was used to further investigate subunit homologies and differences in antigenicity and functional regulation between IGF I and insulin receptors, IGF I receptor tyrosine kinase was stimulated by a IGF I analog (aIGF I), produced by DNA recombinant technology, pIgG was able to inhibit IGF I receptor kinase activity, thus revealing antigenic homologies between the kinase domains of insulin and IGF I receptors. However the more pronounced inhibition of IGF I receptor-compared with insulin receptor kinase activity by pIgG suggests the existence of different regulatory mechanisms.

Antigen-Antibody Reactions↗
PubMed1986

Effect of insulin receptor autophosphorylation on insulin receptor binding.

Insulin receptor beta-subunit autophosphorylation, the first event occurring after insulin binding, plays a crucial role in modulation of receptor-associated kinase activity towards exogenous substrates and possibly in the transmission of biological signals of insulin. Receptor autophosphorylation strongly depends on insulin receptor occupancy. Till now the effects of receptor phosphorylation on insulin binding itself have not been clarified. In the present report we demonstrate the absence of any feedback mechanism by which insulin receptor activation by phosphorylation affects binding affinity of insulin receptor itself.

Adenosine↗
PubMed1985

Inhibition of insulin and epidermal growth factor (EGF) receptor autophosphorylation by a human polyclonal IgG.

The immunoglobulin G of a polyclonal antiserum (pIgG) from a patient with insulin resistance and hypoglycemia was tested for its ability to inhibit insulin binding and to affect the autophosphorylation of partially-purified insulin receptors extracted from rat liver membranes. pIgG, when added 4 hr prior to insulin, inhibited subsequent insulin binding by 50% at 30 micrograms added protein; however, insulin previously bound to the receptor could not be displaced by a 4 hr subsequent exposure of up to 70 micrograms pIgG. pIgG, independent of its effect on insulin binding, inhibited both basal and insulin-stimulated autophosphorylation of the insulin receptor in a dose-dependent manner with a half maximal effect at 3.3 to 7 micrograms protein. Furthermore, pIgG also reduced basal autophosphorylation of the EGF receptor. The effect of pIgG to inhibit basal autophosphorylation of insulin and EGF receptors, together with its ability to reduce autophosphorylation of insulin receptors fully occupied by insulin, imply that the effect of pIgG on receptor autophosphorylation is largely independent of its effect on ligand binding. Moreover, these findings suggest that pIgG may inhibit autophosphorylation by acting on domains which are similar in the insulin and EGF receptors.

Animals↗
PubMed1985

Influence of cell age and ketoaminic linkage on rapid glycosylation of hemoglobin in human red cells in vitro.

In vitro the rate of synthesis of the aldiminic linkage between Hb and glucose depends on glucose concentration, length of incubation and some other physiological factors. To understand better the regulation of this synthesis and to verify the role of cell age and of basal HbA1 levels on the rate of synthesis of pre-A1, we studied red cells from 7 normal controls and 7 diabetics, with high HbA1 levels. We found that the content of HbA1 (stable glycosylated hemoglobin) is able to negatively affect the rate of synthesis of new pre-A1, according to a curvilinear model. These results suggest that in vitro the glycosylation process is saturable, and that elevated values of HbA1 are able to slow the synthesis of pre-A1 in vitro.

Adult↗
PubMed1985

Insulin receptor regulation in human mature red cells in vitro.

We have studied the ability of mature red cells to regulate the number and affinity of their insulin receptors, in vitro. Our data show that mature red cells are not able to change either the number and the affinity of their insulin receptors, after preincubation with high concentrations of insulin alone or insulin and glucose. We conclude that mature red cells possess an insulin receptor system not completely similar to that of major target cells such as hepatocytes and adipocytes, and therefore we suggest some criticism in evaluating these cells in clinical studies, regarding the insulin receptor status.

Animals↗
PubMed1985

Insulin receptor binding on red cells of hypertriglyceridemic patients. Effect of a low fat, low carbohydrate diet.

Insulin binding on circulating red cells has been studied in hypertriglyceridemic (HTG) patients before and after normalization of plasma TG levels by a low fat and low CHO diet, followed for 2 months. Under basal condition HTG patients showed lower insulin binding on red cells (B/T) than control subjects. The reduction in binding was due to a lower receptor number (binding capacity). After the diet and normalization of TG levels, insulin binding was identical in HTG patients and always lower than in controls. The fasting values of blood glucose, IRI, FFA, were also unchanged after TG reduction, suggesting, together with the low insulin binding, a state of insulin resistance. We conclude that our lean patients, affected by HTG, present a state of insulin resistance. Despite normalization of plasma TG, obtained with diet alone, insulin receptor binding on red cells in unchanged.

Cholesterol↗
PubMed1984

Insulin binding on MOLT 4 cells: effect of a sulfonylurea.

Cultured neoplastic cell lines are widely considered an adequate model for insulin receptor studies. In this work the insulin receptor of a well-known continuous T-cell line (MOLT 4) was characterized. These cells showed specific insulin receptor with binding properties quite similar to those of other lymphoblastoid cells. Therefore, we used MOLT 4 receptor to evaluate the effect of the sulfonylurea glipizide on insulin binding. After a 24-hour preliminary incubation of cells with glipizide, we found a 44% increase of insulin receptor binding apparently due to an increase of insulin binding sites.

Cell Line↗