Search PubMed⌕ Search

Biomedical subjects

A Tiengo

Publications and source records attributed to A Tiengo.

At least 127 records · Page 7Linked to original sources

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↗

P.A.S. positive index of lymphocytes and metabolic control in insulin-treated and type II diabetes mellitus.

The relationship between metabolic control and glycogen lymphocyte content in diabetes mellitus, was studied. 30 insulin-treated and 30 type II diabetic subjects were evaluated with 40 age and sex matched normal controls. Glycaemic control was evaluated by a fasting and 2 h post-prandial plasma glucose and by glycosylated hemoglobin (GHb). Glycogen lymphocyte content was determined by calculation of the PAS-positive Index of the lymphocytes (PIL) according to Skrabalo. While fasting and post-prandial plasma glucose values were significantly higher in insulin-treated than in type II diabetes (p less than 0.001), no differences in GHb values were observed between the two groups (10.31 +/- 0.23% vs 9.80 +/- 0.36%). The mean PIL values were not different in these two groups (0.11 +/- 0.01 vs 0.12 +/- 0.02), but they were significantly higher when compared with control values (0.03 +/- 0.004, p less than 0.001), PIL was positively correlated with GHb in both insulin-treated (r = 0.76, p less than 0.001) and type II diabetes (r = 0.55, p less than 0.001). A correlation between PIL and plasma glucose values was observed only in the insulin-treated group and was weaker (p less than 0.005). No correlation was observed between glycogen lymphocyte content and glucose tolerance in the control group. These data confirm that diabetes mellitus is characterized by a significant increase of PAS-positive lymphocyte content and that it correlates well with glycaemic control.

Adolescent↗

Absence of islet alpha cell function in pancreatectomized patients.

Plasma immunoreactive glucagon, C-peptide and substrates (glucose, lactate, and alanine) were measured in 21 pancreatectomized patients and 28 patients with chronic calcifying pancreatitis during arginine infusion. Results were compared with those obtained in control and in insulin-dependent diabetic subjects, and in pancreatectomized subjects receiving a combined infusion of glucagon and arginine or somatostatin and arginine. Plasma immunoreactive glucagon in the pancreatectomized patients was 230 +/- 26 pg/ml (control subjects 100 +/- 13 pg/ml, p less than 0.001), but was unchanged following arginine or somatostatin. Following ethanol extraction of plasma it became undetectable. Similar results were obtained in patients with chronic pancreatitis. In contrast to the insulin-dependent diabetic subjects, no changes in blood glucose, lactate, and alanine concentrations were found during arginine infusion in the pancreatectomized or pancreatitis patients. Addition of glucagon restored the metabolic response to arginine in the pancreatectomized patients. Our results confirm previous smaller studies that in pancreatectomized patients, A cell function is absent or insignificant.

Adult↗

Model of the kinetics of ketone bodies in humans.

The kinetics of ketone bodies was studied in normal humans by giving a combined bolus intravenous injection of labeled acetoacetate ([14C]AcAc) and D(--)-beta-hydroxybutyrate (beta-[14C]-OHB) to seven subjects after an overnight fast, on two different occasions, and by collecting frequent blood samples for 100 min. Kinetic data were analyzed with both noncompartmental and compartmental modeling techniques. A four-compartment model, representing AcAc and beta-OHB in blood and two equilibrating ketone body compartments, inside the liver and extrahepatic tissues, was chosen as the most reliable mathematical representation; it is physiologically plausible and was able to accurately fit the data. The model permitted evaluation of the in vivo rate of ketone body production in the liver, the individual plasma clearance rates of AcAc and beta-OHB, their initial volumes of distribution, and the transfer rate parameters among the four ketone body compartments. Moreover, the model provided estimates of the components of the rates of appearance of AcAc and beta-OHB in plasma due to newly synthesized ketone body from acetyl-CoA in the liver, and to interconversion and recycling in the liver and extrahepatic tissues. The model also was used to evaluate other methodologies currently employed in the analysis of ketone body turnover data: the conventional approach based on use of the combined specific activity of AcAc and beta-OHB required assumptions not satisfied in vivo, leading to substantial errors in key parameter estimates.

3-Hydroxybutyric Acid↗

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↗

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↗

Hormonal and metabolic characteristics of genetically obese Zucker and dietary obese Sprague-Dawley rats.

The endocrine-metabolic plasma pattern and the capacity of isolated perfused livers to produce triglycerides and ketone bodies have been studied in genetically and diet-acquired obese rats (Zucker and Sprague-Dawley obese rats), and in control groups of the same strains. An increased plasma insulin/glucagon molar ratio with hyperinsulinaemia and hypoglucagonaemia was associated with hypertriglyceridaemia, normal ketonaemia, elevated free fatty acids and normal or slight hyperglycaemia in obese rats. During oleate perfusion, the livers of Zucker and Sprague-Dawley obese rats showed an increase in triglyceride output and liver triglyceride content. The ketone body output as well as the mitocondrial carnitine palmitoyl transferase activity were normal or slightly decreased. In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglyceride output has been found.

Animals↗

Hypolipemic glucagon activity in isolated liver of genetic or acquired hypertriglyceridemic rats.

The glucagon effect (150 microgram/3 hrs) on isolated oleate-perfused (1.67 microEq/min) liver has been determined both in fa/fa obese hyperlipemic Zucker and diet-induced hyperlipemic Sprague Dawley rats and in the respective lean strains. Glucagon exerted a normal hypotriglyceridemic effect in hyperlipemic as well as in non-hyperlipemic rats. The ketone body output and the triglyceride liver content were not significantly modified by glucagon. Our data suggest that there is a normal liver responsiveness to the hyolipidemic action of glucagon and, consequently, that there is no glucagon resistance in genetically or diet-induced hyperlipermic rats.

Animals↗

Motor conduction velocity (MCV) in insulin-dependent and non-insulin-dependent diabetics with and without clinical peripheral neuropathy.

Motor nerve conduction velocity (MCV) was determined in the external sciatic popliteus nerve in 83 subjects (46 males and 37 females), 33 with insulin-dependent and 50 with noninsulin-dependent diabetes, with or without clinical signs of diabetic neuropathy. Duration of known diabetes ranged from one month to 32 years. No difference was observed in MCV between insulin-dependent and non-insulin-dependent diabetics. MCV was inversely correlated (p < 0,05) with age, but not with the duration of the disease or with metabolic control. Duration and metabolic control were related to the appearance of clinical signs of peripheral neuropathy.

Adolescent↗

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↗

Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies.

Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the CIA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.

Adult↗

[Clinical and metabolic aspects of juvenile myocardial infarct].

A clinical and metabolic study of 61 patients with myoocardial infarct before the age of 40 yr showed a high frequency of familial involvement, particularly in subjects with type IIA and IIB hyperbetalipoproteinaemia. Excess weight and arterial hypertension were rare, while premonitory angina was absent in 59%. Four subjects were diabetic. Oral glucose tolerance was normal in 14 and of diabetic type in 26 of 40 patients examined; the insulin response pointed to insulin-resistance. Dyslipidaemia was noted in 45%, including type IIA and IIB hyperbetalipoproteinaemia in 27%. Distribution of the frequency of infarct in function of cholesterolaemia classes gave a bimodal curve indicative of distinct normo- and hypercholesterolaemic groups within the series. Reduced glucose tolerance was more frequent in patients with low blood cholesterol. This suggests that reduced tolerance and high blood cholesterol are independent risk factors in coronary disease. No relation between the clinical and metabolic data could be ascertained.

Adult↗