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Biomedical subjects

R Navalesi

Publications and source records attributed to R Navalesi.

At least 163 records · Page 9Linked to original sources
PubMed1976

Insulin kinetics after portal and peripheral injection of [125I] insulin. I. Data analysis and modeling.

The kinetics of insulin are commonly investigated by intravenous administration of labeled hormone, whereas native insulin is removed by the liver to some extent before mixing in the systemic circulation. A mathematical model has been developed which makes it possible to interpret the experimental data obtained by peripheral plasma sampling after portal and peripheral injection of the tracer. Equations are given that allow for the computation of metabolic clearance rate, initial distribution volume, production rate, and body mass of insulin. It is demonstrated that hepatic extraction can be calculated from the difference between the clearance rate values obtained after portal and peripheral injection of the tracer; an estimate of total hepatic catabolism is also derived. The assumptions and limitations underlying this mathematical analysis are discussed.

Infusions, Parenteral↗
PubMed1976

Insulin kinetics after portal and peripheral injection of [125I] insulin: II. Experiments in the intact dog.

Insulin metabolism in man is usually investigated by peripheral injection of the hormone, whereas native insulin undergoes hepatic extraction prior to mixing in the general circulation. To quantify this difference, in 10 dogs [125I] insulin was injected into a peripheral vein, and the initial distribution volume (IDV), the metabolic clearance rate (MCR), and the mean transit time (t) were computed from the plasma disappearance curve of the immunoprecipitable activity. The splenic vein was then cannulated under pentobarbital anesthesia, and the parameters were again computed from the peripheral activity after portal introduction of the tracer. The MCR after portal injection [15.1 +/- (SE) 1.1 ml/min per kg] was greater (P is less than 0.001) than the MCR after peripheral administration (13.4 +/- 0.9 ml/min per kg). Also, IDV was larger (P is less than 0.01) after portal injection (167 +/- 12 vs. 138 +/- 10 ml/kg). Mean transit times did not change significantly. Insulin secretion rate (0.29 +/-0.04 mU/min per kg) and body insulin mass (7.03 +/- 1.5 mU/kg) were also measured. An estimate of hepatic extraction was obtained from the difference between the clearance rate values calculated following portal and peripheral injection. Under our experimental conditions, hepatic retention of insulin was found to be 19.6% (range 9.6-36.2%). The method is recommended for investigations in man.

Animals↗
PubMed1975

Growth hormone kinetics in diabetic patients.

Several reports have shown that average plasma GH concentrations in insulin-treated and in juvenile diabetics are elevated in respect to normal values: these findings have been alternatively attributed to an increased pituitary GH secretion or to a lower GH catabolism induced by the disease. To reinvestigate the problem we studied GH kinetics in twenty-four diabetics using 125-I-GH. The patients were all normal in body weight and their fasting blood sugar did not exceed 190 mg. per 100 ml.; fourteen normal subjects were included as a control group. After single injection of the tracer, the plasma disappearance curve of labeled hormone was obtained. Starting from this curve, metabolic clearance rate (MCR), fractional catabolic rate (FCR), initial distribution volume (IDV), and total distribution volume (TDV) were computed; MCR and plasma concentration of endogenous GH in plasma samples were used to estimate the amount of hormone irreversibly lost during the experiment (IHL240). The major points that result from the comparison of the values obtained in diabetic patients with those in the normal group are: MCR values in diabetics do not differ from those found in normals (63.6 plus or minus 19.6 and 64.6 plus or minus 24.3 ml./min./m.-2 respectively). The higher plasma concentrations of endogenous GH in diabetics together with a normal MCR, yield hormone loss values (IHL240) significantly larger than normal (46.4 plus or minus 29.5 mug/240 min. as compared to 23.7 plus or minus 24.5) thus indicating that an increased GH secretion is present in diabetics. TDV, fairly constant in normals, (5.8 plus or minus 0.9 L./ml-2) tends to decrease in diagetic patients as the disease progesses; in fact the values of TDV are significantly reduced (P less than 0.005) in long-term diabetics (greater than 10 yrs. of disease) while TDV of short-term diabetics (less than 10 yrs.) does not differ from the normal value (4.6 plus or minus 1.16 L./m.-2 and 5.8 plus or minus 0.9 L./m.-2, respectively).

Adolescent↗
PubMed1975

[Insulin].

After a short survey of the different methods for the radioimmunological dosage of insulin, the significance of insulinaemia in fasting conditions and of the insulinaemic curves after stimulation is taken into consideration as regards some physiological aspects. Dosage of insulin in the study of various pathological conditions, such as obesity and diabetes, is throughly examined, also in order to point out its possible diagnostic limitations. The kinetic aspects concerning the hormone situation and requiring the knowledge of other parameters are studied. The remarkable diagnostic usefulness of insulinaemia measurement in the differential diagnosis of hypoglycemic syndromes is pointed out.

Adolescent↗
PubMedDate not supplied

Effects of prolonged exposure to pancreatic glucagon on the function, antigenicity and survival of isolated human islets.

BACKGROUND: Certain clinical conditions are associated with inappropriately high levels of circulating glucagon. To date, little information is available about the direct effects of prolonged exposure of human islet cells to pancreatic glucagon. In the present study we evaluated the function, antigenicity and survival of human islets exposed for 24 h to human pancreatic glucagon. METHODS: We prepared human islets of Langerhans by collagenase digestion and density-gradient purification, incubated them for 24 h with 44 or 430 pmol/l pancreatic glucagon at physiological (5.5 mmol/l) glucose level, and evaluated their insulin release function, which was then compared with that obtained from islets kept at high (11.1 mmol/l) glucose concentration. In addition, aliquots of the islets were evaluated to assess their chemotactic properties towards human monocyte-macrophage cells, and their potency to induce cytokine release from human lymphocytes. Finally, survival of the islet cells cultured under varying conditions was evaluated, and an assessment was performed of mRNA expression of Bcl-2 and Bax proteins. RESULTS: The insulin secretion results demonstrated that, compared to the control islets, the islets previously exposed to either 44 or 430 pmol/l glucagon exhibited changes in insulin release in response to glucose, consisting of augmented secretion at low glucose challenge, and no further significant increase at high glucose stimulation, similar to the effects observed with islets pre-cultured with high glucose. These effects were reversible, as documented by the recovery of normal islet sensitivity to glucose after an additional 24-h culture in medium lacking glucagon. Compared to control islets, the culture medium from islets pre-cultured with high glucagon or high glucose showed an increased chemotactic potency towards human monocyte-macrophage cells. In addition, human lymphocytes released a greater amount of tumour necrosis factor alpha when co-cultured with the islets pre-exposed to high glucagon or high glucose, whereas no significant difference was observed (in comparison with control islets) as regards the release of gamma-interferon, interleukin-2 and interleukin-10. The TUNEL technique and RT-PCR showed, respectively, no major difference in cell survival and expression of mRNA encoding for Bcl-2 and Bax protein between control islets and islets kept for 24 h in the presence of high glucagon or high glucose. CONCLUSIONS: Our results show that in vitro exposure of human islets to pancreatic glucagon for 24 h causes changes in the function and antigenicity of isolated human islets that are similar to the changes observed after pre-culture with increased glucose levels. Under our experimental conditions, these changes were not accompanied by any evidence of cytotoxicity.

Cell Survival↗
PubMedDate not supplied

Hypoglycemia associated with a leiomyosarcoma of the small bowel.

A patient with recurrent hypoglycemic episodes associated with a leiomyosarcoma of the small bowel is described. Fasting plasma insulin levels were consistently low and a subnormal insulin response to provocative stimuli (oral glucose and i.v. glucagon) was shown. After removal of the tumor, hypoglycemic episodes disappeared, fasting plasma insulin concentrations rose to normal values and insulin response to both OGTT and glucagon test was markedly enhanced. The possible mechanisms responsible for the hypoglycemia and the causes of subnormal insulin response to provocative stimuli are discussed.

Aged↗
PubMedDate not supplied

Colorimetric versus radioimmunological measurement of glycated and non-glycated serum albumin after affinity chromatography.

Affinity chromatography by m-aminophenylboronic acid has been proposed for routine measurement of glycated albumin. We assayed glycated and non-glycated fractions of serum albumin (HSA) eluted by affinity chromatography columns by both a specific RIA method for the human serum albumin (HSA) and by a colorimetric method. Sixteen diabetic patients presented a significantly higher percentage of glycated-HSA than 7 control subjects with both methods, and a strong correlation was found between the values obtained with the two methods. RIA was able to detect a significant concentration of glycated-HSA in all normal subjects, while the colorimetric method was not. The accuracy of separation between the glycated and non-glycated fractions of albumin was tested using [14C]glucose as tracer. When [14C]glycated-HSA purified by Sephadex G25 filtration was chromatographed using the m-aminophenylboronic acid, only 5.3% of the total 14C-radioactivity present in the solution was recovered in the bound fraction, while 44.0% was eluted in non-protein-bound fraction and 54.7% was retained in the column. Our findings confirm that affinity chromatography by m-aminophenylboronic acid can be a useful tool in the monitoring of short glycemic control of diabetic patients. Our data also indicate that the affinity chromatography with m-aminophenylboronic acid does not accurately discriminate between glycated and non-glycated fraction of HSA.

Adult↗
PubMedDate not supplied

Inappropriate growth-hormone (GH) response to thyrotropin-releasing hormone (TRH) occurs infrequently in well-regulated diabetes mellitus.

We randomly administered thyrotropin-releasing hormone (200 micrograms, as an i.v. bolus) or control saline (in isovolumic amount) to 30 male diabetic subjects (23 IDDM, 7 NIDDM) in fair metabolic control (HbA1 9.7 +/- 0.3%, means +/- SEM) and to 12 healthy male controls on two different mornings. While GH in the basal state was similar in IDDM, NIDDM and normal subjects, TRH administration evoked a significant GH release only in a single IDDM individual. The only GH-responder to TRH was a newly-diagnosed (two weeks) IDDM patient, still with a high glycated hemoglobin level (HbA1 11.1%), despite normal plasma glucose levels. Saline infusion did not affect GH concentrations either in normals or in diabetics. Exaggerated GH responses to TRH are uncommon in diabetic patients in good metabolic conditions.

Adult↗
PubMedDate not supplied

Low dose metformin in the treatment of type II non-insulin-dependent diabetes: clinical and metabolic evaluations.

Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88 +/- 21.11 mg/dl to 131.12 +/- 16.02 mg/dl after 1 week and to 130.11 +/- 13.29 mg/dl after 5 weeks (p less than 0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33 +/- 24.11 mg/dl to 174.66 +/- 23.45 mg/dl (p less than 0.0025) after 1 week and to 177.65 +/- 21.71 mg/dl (p less than 0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p = n.s. after 1 week, p less than 0.025 after 5 weeks) and serum fructosamine (p less than 0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and beta-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week; insulin binding to monocytes increased slightly but significantly (p less than 0.05) and the number of receptors per cell rose (p less than 0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin-related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic gluconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.

3-Hydroxybutyric Acid↗
PubMedDate not supplied

Biosynthetic human insulin does not modify circulating lipid and apolipoprotein concentrations in type I diabetic patients.

Since insulin modulates key enzymes of lipid metabolism, different biological activities of biosynthetic human insulin (BHI) and conventional insulins might induce different plasma lipid and apolipoprotein patterns in diabetic patients chronically treated with the former or the latter insulin preparation. In this study we have evaluated the effects of 3 months of therapy with BHI on plasma lipid and apolipoprotein concentrations in a group of type I diabetics previously treated with insulin of animal origin and the results have been compared with those from diabetics maintained on conventional insulin therapy. In the latter, no change occurred in the clinical and metabolic parameters. Patients transferred to BHI showed lower HDL-cholesterol and HDL3-cholesterol levels at 30 days from the beginning of BHI treatment, and both parameters returned to, and were maintained the basal values at subsequent controls. Total cholesterol, HDL2-cholesterol, triglycerides, apolipoproteins AI, AII and B remained substantially constant throughout the study. Glycometabolic control, which was evaluated by fasting plasma glucose and glycosylated hemoglobin, exhibited a transient, moderate deterioration at the 30-day control, and returned to basal level in the following weeks. No major change was noted as far as daily insulin dosage and relative body weight were concerned. Thus, long-term BHI treatment of type I diabetics does not cause any major change in plasma lipid and apolipoprotein patterns in comparison with animal insulin therapy, so that the validity of using BHI in the treatment of type I diabetes is confirmed.

Adult↗
PubMedDate not supplied

Guar-pasta: a new diet for obese subjects?

A pasta containing 10% guar-flour was successfully prepared and administered to ten obese women in a seven-day experimental design which included: a control meal (day 1) containing alimentary wheat-pasta, a first guar-pasta meal (day 2), to assess the acute effects of guar-pasta, a second guar-pasta meal (day 7), performed after four days of a weight-maintenance diet containing one guar-pasta meal per day. Compared to wheat-pasta, guar-pasta significantly lowered glucose and insulin response, as well as fasting total cholesterol. Moreover, it had excellent palatability and no gastrointestinal side-effects.

Adult↗
PubMedDate not supplied

'Microalbuminuria' in type I (insulin-dependent) diabetic patients with and without retinopathy.

We investigated the frequency of microalbuminuria (albumin excretion rate, AER greater than 15 micrograms/min) ('overnight' urine collection and radioimmunological evaluation) and its relation to retinopathy (assessed by fluorangiography) in 113 type I (insulin-dependent) diabetic subjects (aged 31 +/- 13 years; diabetes duration 11 +/- 7 years), all Albustix-negative. Sixty eight patients (60.2%) were free of retinal lesions, 31 (27.4%) had background retinopathy and 14 (12.4%) had proliferative retinopathy. Microalbuminuria was found in 25 patients (22%). Fifteen patients (13%) showed both retinopathy and microalbuminuria. Fifteen % (10/68) of the patients with no retinopathy and sixteen % (5/31) of those with background retinal lesions had microalbuminuria, while 29% (4/14) of the patients with proliferative retinopathy were normoalbuminuric. Among the 29 patients with diabetes for less than five years, 1 had retinopathy and 4 had microalbuminuria. Out of 15 patients with both retinopathy and microalbuminuria, 13 (87%) had had diabetes for more than 10 years. Diabetic retinopathy is more frequent than microalbuminuria (40 vs 22%). Although the linkage between retinopathy and microalbuminuria is weak, after ten years of diabetes the two complications may frequently coincide.

Adolescent↗