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Biomedical subjects

A Valerio

Publications and source records attributed to A Valerio.

At least 91 records · Page 5Linked to original sources
PubMed1987

Insulin receptors on circulating blood cells from patients with pancreatogenic diabetes: a comparison with type I diabetes and normal subjects.

We studied 125I-insulin binding to erythrocytes from 14 patients with diabetes secondary to chronic pancreatitis or pancreatectomy and compared the results with those found in 10 patients with type I diabetes and 25 normal controls. Patients with pancreatogenic diabetes had higher 125I-insulin binding and enhanced tissue sensitivity to exogenous insulin measured with the glucose clamp technique as compared with patients with type I diabetes. Similar binding data were obtained with monocytes from 3 patients with pancreatogenic diabetes. The increase in insulin binding seemed due mainly to an increase in receptor number. The increase in insulin binding to cells from patients with pancreatogenic diabetes in comparison with cells from normal subjects was also seen in young-erythrocyte-rich fractions and in old-erythrocyte-rich fractions obtained from the mixed population of circulating erythrocytes by centrifugation in density gradient of Percoll-Pielografin. These data, in the absence of any sign of major hematological disorders, suggest that the increase in insulin receptors seen in erythrocytes and in monocytes from patients with pancreatogenic diabetes, can mirror a general phenomenon on tissues throughout the body, including major target cells for insulin and correlate with the heightened sensitivity to insulin characteristic of these patients. In conclusion, patients with pancreatogenic diabetes have increased insulin binding as compared to controls and to patients with type I diabetes with chronic hypoinsulinemia of the same degree. Thus, in addition to insulin deficiency, other factor (s), such as glucagon deficiency, are responsible for the clinical and metabolic differences between these two conditions of insulin deficiency.

Blood Cells↗
PubMed1987

Metabolic control of kidney hemodynamics in normal and insulin-dependent diabetic subjects. Effects of acetoacetic, lactic, and acetic acids.

Diabetes mellitus is associated with important changes in renal hemodynamics. The purpose of this study was to determine whether an increase in blood concentration patterns of ketone bodies and lactic acid, organic acids often elevated in poorly controlled insulin-dependent diabetes mellitus (IDDM), could contribute to increase glomerular filtration rate (GFR) and renal plasma flow (RPF) regardless of changes in circulating levels of glucose and insulin. Six IDDM patients and six normal subjects were given a saline infusion (15 mumol.min-1.kg-1) for 2 h, an acetoacetic acid infusion (15 mumol.min-1.kg-1) for another 2 h, and then a saline infusion after an overnight fast during euglycemic insulin-glucose clamp. Acetoacetic acid infusion resulted in an increase of blood ketone bodies in the range of 0.7-1.5 mM from a basal value of 0.1-0.3 mM. GFR was 125 +/- 16 and 136 +/- 17 ml.min-1.1.73 m-2 in normal and IDDM subjects, respectively, during baseline saline infusion and 138 +/- 21 (P less than .01 vs. basal level) and 158 +/- 15 ml.min-1.1.73 m-2 (P less than .001 vs. basal level) during acetoacetic acid infusion. During the last saline infusion, renal hemodynamic patterns decreased again to baseline levels. Another six IDDM patients and six normal subjects were given saline, lactic acid, and saline infusions at the same rates of infusion after an overnight fast during euglycemic insulin-glucose clamp. Lactic acid concentration increased from approximately 0.5-0.8 to 1.0-1.5 mM in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1987

Alcohol impairs insulin sensitivity in normal subjects.

The effects of alcohol on insulin action are not yet clearly established. To assess the effects of intravenously administered ethanol on insulin mediated glucose disposal, euglycaemic clamps at 3 different plasma insulin levels and insulin receptor binding studies on circulating monocytes after alcohol infusion were performed. Ethanol infusion leads to a significant reduction of insulin mediated glucose disposal (7.08 +/- 0.4 vs 8.6 +/- 0.6 mg/Kg/min; 9.8 +/- 0.7 vs 13.4 +/- 0.7; 14.7 +/- 0.7 vs 18.1 +/- 0.7 at 33, 73 and 760 mU/m2/min insulin infusion rate respectively). Monocyte insulin-receptor binding was decreased in all the subjects from 30 to 60% after ethanol infusion. These results demonstrate that alcohol can adversely influence the insulin mediated glucose disposal.

Blood Glucose↗
PubMed1986

Alpha cell autoantibodies: immunological and metabolic follow-up study.

We studied glucagon responses to OGTT and insulin and arginine stimulation in 12 out of 21 patients who were found positive for alpha cell autoantibodies (ACA) during routine screening procedures for autoimmunity in a group of 4080 individuals. The study was repeated in 8 subjects after an average observation period of 42 months. In both studies glucagon plasma levels were normal and independent of ACA titres, ACA ability to fix complement and ACA ability to cross-react with duodenal alpha cells. The clinical significance of ACA remains to be elucidated.

Adolescent↗
PubMed1986

Identification of neurotensin receptors associated with calcium channels and prolactin release in rat pituitary.

Neurotensin (NT) is now reasonably well established as a neurotransmitter or neuromodulator candidate in the CNS. In the present study, we characterized the NT receptors in dispersed cells from the anterior lobe of rat pituitary and investigated the involvement of both cyclic AMP and calcium in the release of prolactin (PRL) induced by NT receptor stimulation. The [3H]NT binding to membranes from anterior pituitary dispersed cells was found saturable and stereospecific. Scatchard analysis of the data gave a straight line indicating a Bmax value of 121 +/- 11 fmol/mg protein and a KD value of 1.4 +/- 0.2 nM. The calculated IC50 values for [3H]NT binding were 5.8 nM for NT, 7.8 nM for L-Phe-NT, and 3,000 nM for the pharmacologically inactive form D-Phe-NT. NT, up to a concentration of 1 microM, did not affect the cyclic AMP generating system in homogenates of anterior pituitary from male or lactating female rats. The same pattern of results was obtained for cyclic AMP formation in intact cells. NT and its analogs stereospecifically enhanced the influx of calcium into dispersed cells from rat anterior pituitary. The effect was time- and dose-dependent. It appeared to be associated with neurotransmitter-operated calcium channels since: preincubation of the cells with tetrodotoxin did not affect the increase in calcium influx induced by NT; concentrations of verapamil that counteract the influx of calcium induced by potassium lacked the capacity to modify the influx of calcium induced by NT; and NT lost its capacity to release PRL in the absence of extracellular calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Dopaminergic inhibition of prolactin release and calcium influx induced by neurotensin in anterior pituitary is independent of cyclic AMP system.

The present study demonstrates that 3,4-dihydroxyphenylethylamine (DA, dopamine) prevents neurotensin (NT) stimulation of both prolactin (PRL) release and calcium influx by interacting with specific receptors that are functionally linked to calcium channels. As shown by the studies with dispersed cells from rat anterior pituitary, the pharmacology of the control of PRL release and calcium influx, both induced by NT, was found to be typical of a DAergic process. This was demonstrated by the order of potency of agonists in inhibiting PRL release and calcium influx (DA greater than epinephrine greater than norepinephrine much greater than isoproterenol); by the high affinity of antagonists such as haloperidol and fluphenazine for this process; and by the high degree of stereoselectivity of sulpiride. Specific D2 receptor agonists, such as bromocriptine and lisuride, and the specific D2 receptor antagonist (-)-sulpiride were found to be highly potent on the DA receptors negatively coupled with calcium channels and PRL release. DA was found to lack the capacity to change the influx of calcium induced by either the sodium channel activator veratridine or high extracellular potassium levels, thus indicating a specific action of this amine on calcium channels sensitive to NT. In a range of concentrations that are effective in inhibiting either the calcium influx or the PRL release, both induced by NT, DA did not alter the cyclic AMP generating system. DA (from 1.0 nM to 50 nM) did not affect adenylate cyclase activity in rat pituitary gland homogenates and did not modify intracellular cyclic AMP levels in pituitary cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1985

Glycosylated serum proteins in diabetic patients and their relation to metabolic parameters.

Glycosylated plasma proteins (GSP) and some metabolic parameters (plasma glucose profile, urine glucose excretion, glycosylated hemoglobin, cholesterol, triglycerides) were evaluated in 70 diabetic and 70 normal subjects. Of the late diabetic complications, retinopathy, nephropathy and somatic neuropathy were evaluated. Proliferative retinopathy was observed in 41 of the 70 diabetics studied. No retinopathy or background retinopathy was observed in 29 diabetics. Nephropathy was diagnosed in 39 patients and somatic neuropathy in 44 patients; 26 diabetic subjects had no complications. GSP levels were 0.82 +/- 0.03 nmolHMF/mg prot in diabetics and 0.43 +/- 0.02 nmolHMF/mg prot in controls. GSP levels were positively correlated with metabolic parameters evaluated the same day and 14 days before. A positive correlation between GSP and triglycerides was seen for the first time. The patients with retinopathy showed levels of GSP significantly higher (p less than 0.001) in respect to patients with background retinopathy or absence of it (0.91 +/- 0.03 vs 0.74 +/- 0.04 nmolHMF/mg prot). GSP were significantly higher in the patients with somatic neuropathy (0.93 +/- 0.02 nmolHMF/mg prot) (p less than 0.001) than in the subjects without neuropathy (0.72 +/- 0.04 nmolHMF/mg prot). GSP levels were 0.92 +/- 0.03 nmolHMF/mg prot in diabetics with proteinuria and 0.75 +/- 0.04 nmolHMF/mg prot in diabetics without proteinuria (p less than 0.001). These results confirm the importance of GSP determination as another parameter of glycemic control and particularly as an index of the overall protein glycosylation processes.

Adult↗
PubMed1985

Is red cell sorbitol content a good marker of glycemic control in diabetic patients?

Red cell sorbitol (RCS) concentration and some metabolic parameters were evaluated in 62 diabetic patients. 42 normal subjects were studied as controls. RCS levels were 66.1 +/- 2.0 nmol/gHb in diabetic patients and 41.8 +/- 2.0 nmol/gHb in controls (p less than 0.001). RCS levels were positively correlated with all metabolic parameters evaluated in diabetic patients and in controls. To evaluate RCS distribution, diabetic subjects were subdivided in 3 groups according to fasting plasma glucose (FPG) (less than or equal to 150; 151-200; greater than 200 mg/dl) and glycosylated hemoglobin (GHb) levels (less than or equal to 8; 8.1-10; greater than 10%). 31 patients with FPG less than or equal to 150 mg/dl, all except 7, had RCS levels in the normal range. These 7 patients however had GHb levels greater than 10%. 18 patients with FPG between 151-200 mg/dl had RCS levels in the normal range. Of 13 patients with FPG greater than 200 mg/dl all, except 3, had RCS levels above the normal range. These 3 patients had GHb levels greater than 10%. 45 patients with GHb less than or equal to 10% had RCS values in the normal range. 17 patients with GHb levels greater than 10%, had RCS levels over the normal range. Our data show that RCS levels seem to be related more strictly with GHb. RCS levels increase significantly only in patients with bad metabolic control. Even if RCS levels seem to be a medium-term index of metabolic "equilibrium" they cannot be useful in the routine monitoring of metabolic control in diabetic patients.

Adult↗
PubMed1983

Insulin receptor on monocytes from patients with acromegaly and fasting hyperglycemia.

[125I]Insulin binding to insulin receptors on circulating monocytes was studied in 9 patients with acromegaly associated with fasting hyperglycemia and was compared to previously reported studies of 11 patients with acromegaly who had normal or nearly normal glucose tolerance and 29 normal volunteers. In the hyperglycemic acromegalic, as had been found in the normoglycemic acromegalic, the total receptor concentration per cell was decreased in proportion to the hyperinsulinemia, i.e. the receptor concentration was inversely related to the basal level of insulin, similar to what is found in patients with obesity, diabetes, and insulin-secreting tumors. However, the acromegalic patients with hyperglycemia failed to show the increase in affinity of the empty receptor that had previously been found in their normoglycemic counterparts. The failure to increase receptor affinity causes the cells of the hyperglycemic acromegalic patients to bind less insulin at each insulin concentration than do the cells of normoglycemic patients. Again, the abnormalities in the patients correlates very closely with abnormalities at the level of the insulin receptor, though the sequence of the molecular events that produce these changes remains to be determined.

Acromegaly↗
PubMed1983

Insulin resistance in Cushing's syndrome.

It is well established that cortisol excess causes insulin resistance in man, but the mechanisms responsible for this insulin resistance are poorly understood. We studied five women with Cushing's syndrome with impaired oral glucose tolerance tests and seven normal subjects, plotting the shape of the insulin-induced disposal dose-response curve obtained by means of the euglycemic clamp procedure during four different plasma insulin plateaus at four infusion rates of 21, 73, 760, and 1200 mU/M2 . min. Glucose disposal (M = mg/M2 . min) was calculated as glucose amount infused to maintain euglycemia. In Cushing's syndrome the dose-response curve was shifted to the right in comparison with normal subjects, with a significantly lower M (337 +/- 35 vs. 657 +/- 76 P less than 0.01) during the highest insulin infusion rate [maximal glucose disposal (MGD)] without any significant difference in the levels of insulin half-maximally effective in the stimulation of glucose utilization. Neither erythrocyte nor monocyte maximum insulin receptor binding were different between the two populations. Four Cushing's syndrome patients were studied again after surgical treatment. A marked improvement of MGD was observed without any significant change in insulin-binding capacity. These results, particularly the marked decrease in MGD, a typical feature of postreceptor defects, indicate that cortisol-induced insulin resistance in man is due to an impairment of peripheral insulin action located beyond the hormone-receptor binding step.

Adult↗
PubMed1983

Insulin-mediated glucose disposal in type I diabetes: evidence for insulin resistance.

To clarify whether type I diabetes is characterized by insulin resistance, insulin-mediated glucose metabolism (M; milligrams per kg/min) was estimated by means of the glucose clamp technique in five insulin-dependent diabetic patients and six normal subjects. Three glucose clamps were carried out under different metabolic conditions. Free insulin plateaux were similar during each clamp in both groups. The first clamp was performed in normal subjects after an overnight fast [blood glucose, 80 +/- 3 mg/dl (mean +/- SEM)] and in diabetic patients 18 h after insulin withdrawal (blood glucose, 366 +/- 47 mg/dl). Diabetic patients had a M value (4.25 +/- 0.74) not different from normals (5.38 +/- 0.63; P = NS). The second clamp was done with the same glycemic values (approximately 125 mg/dl) in both groups. M increased to 8.07 +/- 1.06 (P less than 0.01) in the normal subjects and decreased to 2.87 +/- 0.50 (P = NS) in the diabetic patients. The M value in the diabetic patients was lower than that in the normal subjects (P less than 0.05). The third clamp was performed in three diabetic patients after 1 month of treatment with continuous sc insulin infusion. The mean blood glucose level was 88 +/- 6 mg/dl, and M was 3.23 +/- 0.38, significantly lower than that of the normal subjects in the basal state (P less than 0.05). No differences were found in insulin binding to erythrocytes. The mean plasma clearance rate (milliliters per m2/min) of free insulin was the same in both groups (428 +/- 113 in normal subjects and 354 +/- 83 in diabetic patients). Basal endogenous glucose production was higher in the diabetics (3.13 +/- 0.48 mg/kg X min) than in the normal subjects (1.71 +/- 0.57). During the clamp, however, endogenous glucose production was similarly inhibited (approximately 95%) in both groups. Multiple glucose clamp studies were also performed at three different insulin infusion rates (21, 73, and 760 mU/m2 X min, respectively) to generate an insulin-dose response curve for glucose disposal in six diabetic patients treated with continuous sc insulin infusion for at least 6 months. This allowed investigation of the effect of chronic strict insulin therapy leading to normal glucose and intermediary metabolite levels and identification of the cellular mechanism of insulin resistance. A significant reduction of the maximal glucose disposal rate (10.7 +/- 0.5 mg/kg X min) was found in these diabetic patients compared to that in normal subjects (14.9 +/- 1.0; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1981

Effect of ethanol, acetaldehyde, and acetate on insulin and glucagon secretion in the perfused rat pancreas.

The effects of varying concentrations of ethanol (1, 10, and 30 mM) and its metabolites (1 mM acetate and 1 and 10 mM acetaldehyde) on insulin and glucagon secretion induced by glucose (11.1 mM) and arginine (20 mM) were studied in isolated perfused pancreas of Sprague-Dawley rats. Ethanol and its metabolites did not significantly modify basal secretion of the two hormones. Ethanol reduced glucose-induced insulin secretion by means of a dose-related effect. Arginine-induced insulin output did not seem to be influenced to any significant degree. Acetate and acetaldehyde significantly inhibited glucose and arginine-induced insulin secretion. While ethanol (10 and 30 mM ) did not modify glucagon output during arginine perfusion, acetate and acetaldehyde markedly enhanced it. The block of insulin secretion and the increased secretion of glucagon could explain the diabetogenic effect of ethanol demonstrated in vivo. The mechanism by which ethanol acts on the pancreatic beta- and alpha-cells is discussed.

Acetaldehyde↗
PubMed1981

[Vectorcardiographic study in elderly subjects with a normal ECG (author's transl)].

In order to estimate if the elderly subjects with a normal ECG present vectorcardiographic (VCG) changes, were analyzed the VCG of 35 patients of age between 65 and 84 years with a normal ECG, negative anamnesis, objective cardiovascular examination and no radiological alteration of the cardiac image. These patients were divided in two groups according to the age: the first included 20 patients of age between 65 and 74 years, the second 15 patients between 75 and 84 years. A group of control with an average variable between 40 and 59 years, was also examined. The P, QRS and T loops were examined. The P loop, with a lessened magnitude (mV), particularly in second group, was directed inferiorly and anteriorly as regards controls, with initial, middle and/or terminal slurrings. On the QRS loop, in second group, were found the following changes: the Initial Vectors are directed inferiorly and anteriorly, the Maximum Spatial Vector more superiorly and anteriorly and Terminal Vectors more superiorly and posteriorly therefore the loop appeared frequently distorted on the frontal plane. The loop, with a lessened magnitude, particularly in second group, more frequently counter-clockwise inscripted on the frontal plane. Time of occurrence of Maximum QRS Vector (msec) was found more precocious. The T loop, with a lessened magnitude, particularly in second group, resulted slightly deviated inferiorly and anteriorly. The observed changes appeared modest and of a kind more quantitative, that is expressed by changes in the magnitude and relation between different vectorial groups, than qualitative, that is in relation to changes in the orientation and succession of such vectors. These changes, more frequent in the second group patients, don't give generally problems of differential diagnosis with the myocardial infarcts, hypertrophies or conduction disturbances. They are likely in relation to histological and/or metabolic changes in the myocardium common tipic of old age and in a lesser degree to anatomic and haemodynamic changes in the senile heart.

Adult↗
PubMedDate not supplied

Red cell sorbitol concentration in relation to short- and medium-term variation of plasma glucose.

To evaluate the time course of changes in red cell sorbitol (RCS) concentration in relation to variations of plasma glucose levels, RCS was determined in 7 normal subjects during i.v. glucose infusion (IVGTT); in 6 hyperglycemic insulin-dependent diabetic subjects while glycemia was normalized with Biostator GC 115 and in 4 diabetic patients in previously poor metabolic control, in whom normal glycemia was obtained in 8-10 days by intensive insulin therapy. During IVGTT, plasma glucose levels increased with significant differences from baseline at 5, 10, 16, 25, 60, 100 and 160 min and returned to basal levels after 3h; RCS concentration showed small and insignificant increases. During i.v. insulin infusion, plasma glucose fell to almost normal levels within roughly 3h; RCS levels showed a gradual reduction becoming significant at 180 min. In the third study, decrease in plasma glucose was always associated with a fall in RCS level which became significant between the 2nd and the 3rd day of the study. Thus, RCS levels were not affected by very short-term variations of glycemia but by a previous hyperglycemic crisis that lasted a few hours. There were therefore medium-term variations of RCS level. In conclusion, RCS determination is not useful as an index of metabolic control in diabetes.

Activity Cycles↗
PubMedDate not supplied

Plasma and red cell sorbitol assay in diabetic subjects.

Plasma and red cell sorbitol concentrations, fasting plasma glucose, glycosylated hemoglobin (GHb) were evaluated in 30 diabetic patients and 42 normal subjects. Red cell sorbitol levels were evaluated in hemolysate and non-hemolyzed samples. Mean red cell sorbitol concentrations evaluated after hemolysis were 21.5 +/- 5 nmol/ml in diabetics and 12.2 +/- 4 nmol/ml in controls (p less than 0.001). Mean values of red cell sorbitol determined in non-hemolyzed samples were 13.9 +/- 3 nmol/ml in diabetics and 8.1 +/- 3 nmol/ml in controls (p less than 0.001). Mean plasma sorbitol concentrations were 8.4 +/- 3 nmol/ml in diabetics and 5.2 +/- 1 nmol/ml in controls (p less than 0.001). The within and between run reproducibilities evaluated in plasma, hemolysate and non-hemolyzed red cells gave the lowest values for hemolyzed red cell samples. The studies on stability showed that samples neutralized and stored at -20 degrees C gave reproducible values if assayed within 3 days. A positive correlation was found between red cell hemolysate sorbitol concentrations and fasting plasma levels in both diabetics (r = 0.56; p less than 0.001) and controls (r = 0.62; p less than 0.001). Red cell hemolysate sorbitol concentrations were also positively correlated to GHb in both diabetics (r = 0.64; p less than 0.001) and controls (r = 0.36; p less than 0.05). We believe the most effective sorbitol assay to be that obtained in hemolyzed red cells and that these values related to glycemic levels could be a useful index of metabolic control and an indicator of tissue sorbitol levels in humans.

Adult↗
PubMedDate not supplied

Ketone body kinetics in vivo using simultaneous administration of acetoacetate and 3-hydroxybutyrate labelled with stable isotopes.

Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single 14C tracer and the so called 'combined KB specific activity'. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of 14C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administration in vivo of [1,2,13C2] AcAc and m [1,2,3,4(13)C4] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic 13C/12C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of 12C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 +/- 57 mumol/min/1.73 m2 (mean +/- SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 +/- 41. The plasma clearance rates of AcAc and R-BHB were 1966 +/- 502 and 1443 +/- ml/min/1.73 m2, respectively. The mean residence time was 17 +/- 3 min and the total distribution volume 20 +/- 9.7 l/m2. We conclude that: (1) stable isotope tracer infusion allows the contemporary in vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections.

3-Hydroxybutyric Acid↗