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Biomedical subjects

M Muggeo

Publications and source records attributed to M Muggeo.

At least 127 records · Page 7Linked to original sources
PubMed1983

[Correlation of metabolic and hemorrheological parameters in diabetes and hyperlipidemia].

Blood viscosity, plasma viscosity and erythrocyte filterability were studied in 46 diabetic and in 24 hyperlipidemic patients and were compared with those of a group of normal controls; 35 diabetics were type I (IDDM, 13 of whom complication-free and 22 with micro- and macroangiopathy), 11 diabetics were type II (NIDDM, 5 of whom complication-free and 6 with micro- and macroangiopathy). Erythrocyte filterability was lower in type I and II diabetes than in controls, and was also lower in diabetics with vascular complications than in complication-free patients. Erythrocyte filterability inversely correlated with HbA1c and with plasma uric acid levels. The hyperlipidemic group included 6 type IIa, 6 type IIb, 8 type IV and 4 type V patients. All hyperlipidemic patients were examined before and during diet and drug therapy. In all the hyperlipidemic patients blood viscosity inversely correlated with HDL-cholesterol, while plasma viscosity directly correlated with plasma uric acid. All these findings suggest that some hemorheological factors can play a role in the onset and progression of vascular complications of diabetes mellitus and hyperlipidemias, and that the hemorheological changes correlate with the severity of the metabolic abnormalities.

Blood Viscosity↗
PubMed1982

Impaired insulin degradation in a patient with insulin resistance and acanthosis nigricans.

The kinetics of plasma insulin were studied in a 14 year old girl with the syndrome of insulin resistance and acanthosis nigricans. The clearance of plasma insulin was found to be strikingly reduced (135 ml/min . m2 versus 456 +/- 22 in 17 normal control subjects), whereas the basal systemic insulin delivery rate was increased about 10-fold (25.5 mU/min . m2 versus 2.6 +/- 0.3 in normal subjects). Thus, reduced insulin clearance and excessive posthepatic delivery of the hormone both contributed to the severe fasting hyperinsulinemia (218 microunits/ml) associated with the other clinical features of the syndrome (glucose intolerance, primary amenorrhea, polycystic ovaries, hirsutism). Following ovarian wedge resection, insulin clearance rose to 264 ml/min . m2, and insulin delivery fell to 9.8 microunits/ml min . m2. The resulting abatement of the patient's hyperinsulinism (fasting plasma insulin = 37 microunits/ml) was accompanied by the appearance of menses, normalization of glucose tolerance, and amelioration of the acanthosis. The improvement in menstrual function and acanthosis, however, was not sustained. This case provides evidence for interdependence of insulin action and insulin degradation in humans.

Acanthosis Nigricans↗
PubMed1982

Autoantibodies to the insulin receptor and insulin-resistant diabetes.

Autoantibodies to the insulin receptor are a rare cause of insulin-resistant diabetes, but when they occur they produce a profound clinical syndrome. These antibodies block insulin binding, immunoprecipitate solubilized insulin receptors, and their acute effect is to mimic the biological effects of insulin. However, prolonged exposure of cells to these antibodies produces a state of insulin resistance. Since the antigen to which the antibody is directed is relatively well-characterized, many of the observations in this syndrome can serve as a model for elucidating molecular mechanisms in other diseases with antibodies against membrane components. The autoantibodies to the insulin receptor have also provided valuable probes in the study of insulin receptor structure and insulin action.

Adipose Tissue↗
PubMed1982

Insulin sensitivity, binding, and kinetics in pancreatogenic and type I diabetes.

Pancreatogenic diabetes (PD), secondary either to chronic calcific pancreatitis or to pancreatectomy, is characterized by higher frequency of hypoglycemic events during insulin therapy in comparison with type I insulin-dependent diabetes (IDD). Not only glucagon deficiency, but an enhanced peripheral tissue sensitivity to insulin could account for this metabolic behavior. We investigated several facets of insulin action, e.g., tissue sensitivity to insulin, insulin binding to red cells, and insulin kinetics in seven patients with PD in comparison with type I. Tissue sensitivity to insulin was evaluated by means of the glucose-insulin clamp technique as M/I x 100 ratio (mg . kg .-1 min-1/muU . ml-1), where M is the amount of glucose infused by Biostator GCIIS to clamp BG at basal level and I is the free insulin plateau concentration achieved by a primed-constant insulin infusion. At high BG 15 h after the last injection of regular insulin M/I x 100 was 7.79 (range 4.25-9.75) in PD and 4.20 (range 1.20-6.91) in D (P less than 0.05). At low and equal BG M/I x 100 was 8.55 (range 6.35-9.72) in PD and 3.42 (range 1.19-6.75) in D (P less than 0.01). The rate of endogenous glucose production was nearly totally suppressed in both groups of patients. Just before the two clamps, 125I-insulin specific binding to red cells was studied. The maximum specific binding was significantly higher in PD than in D at high BG (10.7 +/- 1.7 vs. 7.4 +/- 0.8/10(9) red cells) and at low and equal BG (12.4 +/- 1.2 vs. 6.8 +/- 0.8). Receptor concentration also was significantly higher in PD thant in D (P less than 0.02) while no significant differences were found in high affinity (Ke). Insulin kinetic data were analysed by using both "Model independent" (or noncompartmental) method and compartmental modeling. Patients with PD had significantly higher (P less than 0.05) plasma clearance of insulin.

Adult↗
PubMed1981

Heterogeneity of the insulin-receptor interaction in lipoatropic diabetes.

[125] Insulin binding to its receptors was studied on circulating cells from 11 patients (8 females and 3 males) with lipoatropic diabetes. The patients ranged in age from 9-54 yr. All were insulin resistant, as evidenced by fasting hyperinsulinemia and insulin tolerance tests. Nine patients were evaluated by specific [125] insulin binding to monocytes. Three different patterns of receptor abnormalities were observed: 3 patients demonstrated decreased binding due to decreased binding capacity, 2 patients revealed normal tracer binding with decreased receptor affinity,, and 4 patients had normal or increased insulin binding. [125] Insulin binding to erythrocytes in 9 cases demonstrated similar heterogeneities of initial binding. In most cases there was a good correlation between the binding with erythrocytes and monocytes, although decreased affinity was not observed in the red blood cells. There was no obvious correlations between the nature of the receptor defect and the clinical patterns in these patients. Heterogeneity in insulin binding was even observed among affected members of the same family. Antibodies to the insulin receptor were not detected in any of these patients by either binding inhibition or immunoprecipitation assays. These data suggest that the pathogenesis of the insulin resistance in lipoatropic diabetes is heterogeneous and may involve both receptor and postreceptor abnormalities.

Adolescent↗
PubMed1980

Characterization of insulin receptors in patients with the syndromes of insulin resistance and acanthosis nigricans.

This report analyzes the in vitro characteristics of 125I-insulin binding to the monocytes of nine patients with the syndromes of acanthosis nigricans and insulin resistance. The 3 Type A patients (without demonstrable autoantibodies to the insulin receptor) had decreased binding of insulin due to a decreased concentration of receptors. In these patients the residual receptors demonstrated normal dissociation kinetics, negative cooperativity, and were blocked by anti-receptor antibodies in a manner similar to normal cells. In contrast, monocytes from the 6 Type B patients (with circulating anti-receptor autoantibodies) had decreased binding of insulin due to a decrease in receptor affinity. Insulin binding to monocytes of Type B patients demonstrated accelerated rates of dissociation with no evidence of cooperative interactions among insulin receptors. When coupled with previous data, the present studies further suggest that different mechanisms account for the defects in insulin binding and insulin resistance observed in these patients.

Acanthosis Nigricans↗
PubMed1979

Regulation of insulin receptors in normal and abnormal physiology in humans.

Insulin receptors in human tissue undergo marked changes in both their concentration and their affinity for insulin. In general, alterations in receptor affinity are associated with rapidly changing metabolic environments and can occur within hours, whereas alterations in receptor concentration appear to require longer time periods for their induction. The association of a given type of receptor alteration (i.e., change in affinity or concentration) with a given clinical state indicates the presence of distinct modulators of the insulin-receptor interaction. We have presented evidence for 2 specific modulators, i.e., insulin itself and anti-insulin-receptor antibodies. In several clinical states, especially those associated with changes in receptor affinity, receptor alterations are unrelated to either ambient insulin levels or anti-receptor antibodies, suggesting the presence of several as yet unknown mediators of the insulin receptor. The direct metabolic consequences of these receptor events are not well established. In several states, the receptor alteration correlated quite well with the clinical sensitivity of the whole organism to insulin, indirectly implicating the receptor as the major control point for insulin sensitivity. In contrast, specific examples were cited in which receptor events are not consonant with observed biologic responses to insulin, thereby suggesting a predominance of postreceptor processes. Finally, it should be emphasized that the study of hormone receptors and their relationship to disease states is in the formative stage. With new and improved methodology we hope we will be able to investigate the entire pathway of insulin action at its target tissues, from the initial receptor binding to the final biologic effect.

Acanthosis Nigricans↗
PubMed1979

Altered control of growth hormone secretion in patients with cirrhosis of the liver.

Ten male patients with cirrhosis of the liver (three with portacaval anastomosis [PCA]) and eight sex- and age-matched controls underwent an arginine infusion test followed by an intravenous glucose tolerance test. Plasma glucose and growth hormone (GH) levels were measured during a period of three hours. In the normal subjects, the peak GH response to arginine occurred 60 minutes after the start of the infusion and was followed by a progressive decline in GH concentration; dextrose injection resulted in a further rapid fall in GH concentration. In cirrhotic patients, both fasting and postarginine GH concentrations were significantly higher than in controls; in addition, the dextrose injection, after causing a transitory drop in plasma GH levels, resulted in a marked increase in plasma GH concentration. In the patients with PCA, the plasma GH increase after arginine and after dextrous was more marked. In these cirrhotic patients, the plasma GH levels correlated directly with the magnitude of the portal hypertension and inversely with the serum albumin concentration, suggesting that the abnormality of GH secretion was a reflection of the derangement in liver function.

Adult↗
PubMed1978

Extreme insulin resistance in ataxia telangiectasia: defect in affinity of insulin receptors.

The syndrome of ataxia telangiectasia is associated with glucose intolerance and insulin resistance. We examined the status of insulin receptors on circulating monocytes and on cultured fibroblasts from two siblings with ataxia telangiectasia and severe insulin resistance. 125I-insulin binding to monocytes of the two patients consistently demonstrated an 80 to 85 per cent decrease in receptor affinity. In contrast, the defect in receptor affinity was not expressed on the patients' cultured fibroblasts or on monocytes or fibroblasts obtained from unaffected family members. Whole plasma and immunoglobulin-enriched fractions of plasma from the patients inhibited the normal binding of insulin to its receptors on cultured human lymphocytes (IM -9 line) and on human placental membranes. We conclude that the insulin resistance in the two siblings with ataxia telangiectasia was associated with defects in the affinity of the receptors for insulin, probably caused by circulating inhibitors of insulin binding.

Acanthosis Nigricans↗