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Biomedical subjects

A Tiengo

Publications and source records attributed to A Tiengo.

At least 109 records · Page 6Linked to original sources
PubMed1986

Hormonal and metabolic profiles in patients with alcohol-induced, mixed hypertriglyceridemia before and after abstinence from ethanol and before and after a lipid-lowering diet.

The diurnal variation of intermediary metabolites and hormones was determined, as 24-h profiles, in a group of subjects with mixed hypertriglyceridemia while consuming a diet with excess alcohol and caloric intake (Hyp-I) or after a hypotriglyceridemic diet (Hyp-II), and in normal controls. Alcohol was excluded from the hypotriglyceridemic diet and on the days of the study. Hyp-I subjects showed higher 24-h levels of plasma triglyceride, glucose, insulin, lactate, pyruvate, free fatty acid and glycerol. After the hypotriglyceridemic diet the levels of pyruvate, free-fatty acids and glycerol in plasma were normalized, while triglyceride, insulin and glucose concentrations were significantly reduced but remained still higher than in controls. The elevated lactate concentration in Hyp-I subjects were unaffected by the diet. In Hyp-I subjects free-fatty acids and glycerol levels were not suppressed following the meal, in contrast to controls. After the diet this defect in the suppression of endogenous lipolysis was only partially reversed in Hyp-II subjects. Plasma alanine, total ketone body and glucagon concentrations were unaffected. In conclusion, in mixed hypertriglyceridemia high lactate concentration and a defect in the suppression of endogenous lipolysis after a meal could represent a factor enhancing triglyceride production.

Adult↗
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

Alcohol intake and withdrawal: effects on branched chain amino acids and alanine.

The effects of chronic alcohol consumption on plasma branched chain amino acids and alanine concentrations were evaluated, and basal blood concentrations of these amino acids were determined after chronic ethanol intake and following a withdrawal period in 30 admitted alcoholics. After ethanol intake, alcoholics showed increased branched chain amino acid concentrations; the blood alanine concentrations were depressed after the withdrawal period. To evaluate the effect of ethanol on diurnal variations of these amino acids in the blood, a group of these patients underwent two isocaloric diets with and without wine. The diet with alcohol induced a sustained increase of branched chain amino acids persisting even after the postprandial phase with a decrease of alanine as compared to the diet without.

Adult↗
PubMed1986

Dose-response curves of effects of insulin on leucine kinetics in humans.

To determine the effects of physiological and pharmacological insulin concentrations on leucine-carbon kinetics in vivo, eight postabsorptive normal volunteers were infused with L-[4,5-3H]leucine and alpha-[1-14C]ketoisocaproate (KIC). Insulin concentrations were sequentially raised from 8 +/- 1 to 43 +/- 6 and 101 +/- 14 and to 1,487 +/- 190 microU/ml, while maintaining euglycemia with adequate glucose infusions. At the end of each 140-min insulin-infusion period, steady-state estimates of leucine and KIC rates of appearance (Ra), KIC (approximately leucine-carbon) oxidation, nonoxidized leucine-carbon flux [an index of leucine incorporation into protein (Leu----P)], and leucine and KIC interconversion rates were obtained. After the three insulin infusions, leucine Ra decreased by a maximum of approximately 20%. KIC Ra decreased by a maximum of approximately 50%. The sum of leucine plus KIC Ra in the basal state was 2.59 +/- 0.24 mumol X kg-1 X min-1 and decreased by approximately 30% at the maximal insulin concentrations. KIC oxidation decreased by a maximum of approximately 65%. Leu----P did not increase after hyperinsulinemia. Interconversion rates were promptly and markedly suppressed by 50-70%. Leucine clearance increased by approximately 120%. We conclude that euglycemic hyperinsulinemia, at physiological and pharmacological concentrations, decreased leucine and KIC concentrations, leucine-carbon turnover and oxidation, and leucine and KIC interconversions in a dose-dependent manner in vivo.

Adult↗
PubMed1986

Urinary glycosaminoglycans, sialic acid and lysosomal enzymes increase in nonalbuminuric diabetic patients.

Urinary excretion of glycosaminoglycans (GAGS) and sialic acid (SA), as well as the activity of two renal enzymes related to glycoprotein metabolism, N-acetyl-beta-D-glucosaminidase (NAG) and beta-galactosidase (GAL), and two others unrelated to glycosaminoglycans and glycoprotein metabolism, gamma-glutamyltranspeptidase (gamma-Gt) and angiotensin-I-converting enzyme (ACE), were evaluated in 40 insulin-dependent diabetic patients with normal range albuminuria, 21 patients with mesangial glomerulonephritis, and 30 control subjects. Diabetic and glomerulonephritic patients excreted a significantly higher amount of GAGS and SA, and showed greater NAG and GAL activities; gamma-Gt and ACE levels were within normal ranges. No correlation could be demonstrated between diabetes duration and GAGS, SA, NAG and GAL findings. Moreover, no correspondence between degree of metabolic control, as reflected by glycosylated hemoglobin (HbA1a-c) and GAGS, SA, NAG and GAL emerged.

Acetylglucosaminidase↗
PubMed1986

Defective suppression by insulin of leucine-carbon appearance and oxidation in type 1, insulin-dependent diabetes mellitus. Evidence for insulin resistance involving glucose and amino acid metabolism.

To determine whether a resistance to insulin in type 1, insulin-dependent diabetes mellitus (IDDM) is extended to both glucose and amino acid metabolism, six normal subjects and five patients with IDDM, maintained in euglycemia with intravenous insulin administration, were infused with L-[4,5-3H]leucine (Leu) and [1-14C]alpha ketoisocaproate (KIC). Steady-state rates of leucine-carbon appearance derived from protein breakdown (Leu + KIC Ra) and KIC (approximately leucine) oxidation were determined at basal and during sequential euglycemic, hyperinsulinemic (approximately 40, approximately 90 and approximately 1,300 microU/ml) clamps. In the euglycemic postabsorptive diabetic patients, despite basal hyperinsulinemia (24 +/- 6 microU/ml vs. 9 +/- 1 microU/ml in normals, P less than 0.05), Leu + KIC Ra (2.90 +/- 0.18 mumol/kg X min), and KIC oxidation (0.22 +/- 0.03 mumol/kg X min) were similar to normal values (Leu + KIC Ra = 2.74 +/- 0.25 mumol/kg X min) (oxidation = 0.20 +/- 0.02 mumol/kg X min). During stepwise hyperinsulinemia, Leu + KIC Ra in normals decreased to 2.08 +/- 0.19, to 2.00 +/- 0.17, and to 1.81 +/- 0.16 mumol/kg X min, but only to 2.77 +/- 0.16, to 2.63 +/- 0.16, and to 2.39 +/- 0.08 mumol/kg X min in the diabetic patients (P less than 0.05 or less vs. normals at each clamp step). KIC oxidation decreased in normal subjects to a larger extent than in the diabetic subjects. Glucose disposal was reduced at all insulin levels in the patients. In summary, in IDDM: (a) Peripheral hyperinsulinemia is required to normalize both fasting leucine metabolism and blood glucose concentrations. (b) At euglycemic hyperinsulinemic clamps, lower glucose disposal rates and a defective suppression of leucine-carbon appearance and oxidation were observed. We conclude that in type 1 diabetes a resistance to the metabolic effects of insulin on both glucose and amino acid metabolism is present.

Adult↗
PubMed1986

Type I diabetes is characterized by insulin resistance not only with regard to glucose, but also to lipid and amino acid metabolism.

Resistance to the metabolic effects of insulin has been reported with regard to glucose disposal in type I diabetic patients (IDDM) even when they were euglycemic. Our aim was to study glucose, lipid, and amino acid metabolism during glucose clamping at multiple levels of insulin in 10 normal (N) and 6 IDDM patients. Blood glucose was maintained constant (4.7 mmol/liter) at three insulin plateaus (160 min each) [42 +/- 6 (SD) 89 +/- 11, and 1255 +/- 185 microU/ml in N and 36 +/- 4, 80 +/- 13, and 1249 +/- 107 microU/liter in IDDM]. Mean glucose disposal was 34 +/- 11, 69 +/- 10, and 84 +/- 22 mumol kg-1 min-1 in N and 16 +/- 5, 40 +/- 18, and 65 +/- 27 in IDDM, respectively. Baseline concentrations of blood lactate, pyruvate, alanine, and branched chain amino acids were 560 +/- 130, 36 +/- 9, 212 +/- 44, and 451 +/- 19 mumol/liter, in N and 793 +/- 179 (P less than 0.05), 45 +/- 14, 195 +/- 50, and 439 +/- 33 in IDDM, respectively. The maximum percent change of lactate during the euglycemic clamp was +147 +/- 23% in N and +75 +/- 15% (P less than 0.05) in IDDM; that of branched chain amino acids was -61 +/- 5% in N and -48 +/- 7% (P less than 0.01) in IDDM. Baseline concentrations of glycerol, FFA, and adipate were 44 +/- 15, 449 +/- 152, and 8 - 8 mumol/liter in N and 39 +/- 14, 473 +/- 44, and 41 +/- 14 (P less than 0.01) in IDDM. The maximum percent change of glycerol during the euglycemic clamp was -50 +/- 8% in N and -16 +/- 8% (P less than 0.01) in IDDM, that of FFA -98 +/- 3% in N and -70 +/- 4% in IDDM (P less than 0.05). No significant differences were found between N and IDDM with regard to blood concentrations of ketone bodies, citrate, ketoglutarate, and hydroxymethylglutaryl coenzyme A both before and during the euglycemic clamp. The lactate percent increase was significantly correlated to glucose disposal rate (P less than 0.001). The lactate turnover rate increased during the euglycemic clamp and was lower in IDDM than in N. We conclude that during euglycemic-multiple insulin clamp studies the greater lactate increase suggests that the flux of glycolysis is higher in N than in IDDM, tricarboxylic acid concentrations are comparable in N and IDDM, and FFA, glycerol, and branched chain amino acid decreases were less in IDDM than in N, suggesting that IDDM patients are resistant to insulin with regard to lipid and protein metabolism. The higher adipate basal values demonstrate enhanced omega-oxidation in IDDM.

Adult↗
PubMed1985

Hyperalaninaemia is an early feature of diabetes secondary to total pancreatectomy.

High levels of gluconeogenic precursors have been reported in patients with long-term diabetes secondary to total pancreatectomy. In the present study, blood concentrations of alanine, lactate and pyruvate were measured in six patients undergoing total pancreatectomy and in nine control subjects undergoing major abdominal surgery. To exclude the simple effect of lack of insulin and hyperglycaemia in the development of hyperalaninaemia following total pancreatectomy, three pancreatectomized patients and five control subjects underwent surgical operation while connected to an artificial pancreas. Blood concentration of alanine was constant in the control subjects during surgery (182 +/- 20 and 243 +/- 31 mumol/l with and without the artificial pancreas, respectively). In pancreatectomized patients basal blood alanine levels were similar to those in control subjects. Blood alanine level rose quickly after removal of the pancreas from 182 +/- 24 to 285 +/- 15 mumol/1 (p less than 0.05) in the patients connected to the artificial pancreas, and from 198 +/- 17 to 395 +/- 47 mumol/1 (p less than 0.05) in patients undergoing total pancreatectomy without artificial pancreas. These values were higher than those observed in the control subjects at the end of the operation (192 +/- 22 and 230 +/- 45 mumol/l with and without artificial pancreas, respectively.) Basal and intraoperative blood concentrations of lactate and pyruvate were similar in pancreatectomized patients and control subjects.

Adenocarcinoma↗
PubMed1985

Hyperaminoacidaemia reduces insulin-mediated glucose disposal in healthy man.

To determine whether hyperaminoacidaemia may modify insulin-mediated glucose disposal, normal subjects were studied with the euglycaemic glucose-clamp technique, with or without an amino acid infusion, at a rate sufficient to duplicate the plasma concentration of most amino acids. Steady-state glucose infusion rates to maintain euglycaemia were 36% lower during hyperaminoacidaemia (7.3 +/- 1.0 versus 11.4 +/- 0.8 mg X kg-1 X min-1, p less than 0.01) at comparable insulin concentrations (92 +/- 6 versus 93 +/- 7 mU/l respectively). Thus, under conditions of hyperinsulinaemia, amino acids could compete with glucose as metabolic fuels.

Adult↗
PubMed1985

Effects of insulin treatment on ketone body production and carnitine-palmitoyl-transferase (CPT) activity in the isolated perfused liver from streptozotocin diabetic rats.

The aim of the present paper was to evaluate the effects of in vivo insulin treatment of streptozotocin (SZ) diabetic rats on the metabolism of the isolated, perfused liver. Perfused livers from SZ-diabetic rats showed a higher ketone body production and a higher mitochondrial carnitine-palmitoyl-transferase (CPT) activity than controls, while triglyceride (TG) output and free-fatty-acid (FFA) uptake were significantly reduced. In vivo insulin treatment normalized both the ketogenic capacity of the liver and CPT activity, while FFA uptake and TG production were still lower than in controls. A significant correlation was found between total ketone body output and CPT activity. We suggest that In vivo insulin treatment of SZ-diabetic rats can modulate the ketogenic capacity of the isolated, perfused liver.

Acyltransferases↗
PubMed1985

Ketone body metabolism in normal and diabetic human skeletal muscle.

Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[14C]hydroxybutyrate (BOH) or [3-14C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V-A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). We assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1985

Survival and rehabilitation after total pancreatectomy. A follow-up of 36 patients.

Thirty-six totally depancreatectomized patients were followed up for 4-124 months. Pancreatectomy had been performed because of fulminant pancreatitis (in 10), chronic hyperalgic otherwise untractable pancreatitis (in 7), exocrine carcinoma of the pancreas (in 16), cystadenocarcinoma of the pancreas (in 2) and insulinoma (in 1). The longest survival duration was in chronic pancreatitis patients: 57 +/- 17 months. A normal socio-professional reinsertion was obtained in 16 patients, mainly those with non-malignant pancreotopathies. At the end of the survey, ten of the carcinoma patients had died, versus none in the other groups. Diabetes mellitus was characterized by the absence of ketonuria, and the frequent occurrence of hypoglycemia (in 15 patients) and infection (in 6). Malabsorption caused osteomalacia in one patient.

Acute Disease↗
PubMed1984

Effect of streptozotocin in a case of glucagon-secreting malignant islets-cell tumor.

A case of a 65-year-old woman with a pancreatic tumor secreting insulin, glucagon, and associated with high PTH levels and hypercalcemia is reported. The patient underwent two Streptozotocin (STZ) treatments (1 g iv/week for 10 weeks) after liver metastases were found. Hormonal and metabolic parameters were monitorized . Before the first STZ treatment insulin levels ranged between 78 and 132 microU/ml. After STZ administration insulin decreased and then remained lower (8-48 microU/ml) until the death of the patient. Pre-treatment glucagon levels ranged between 1.3 and 3.9 ng/ml. STZ induced a decrease of glucagon to 0.5 ng/ml. Glucagon chromatography revealed the prevalence of high molecular weight (greater than 6,000 mol wt) immunoreactive glucagon (0.9 ng/ml) drastically reduced by STZ treatment (0.15 ng/ml). Hypoaminoacidemia was observed before STZ administration, but at the end of the therapy plasma amino acid concentrations were normal. Hypercalcemia too was sensitive to STZ, but not PTH value, which remained high. The second STZ treatment performed a year later was less effective and so a chemotherapeutic protocol was started. Our findings suggest a cytolitic effect of STZ on malignant A-cell, with reduction of glucagon levels and restoration of amino acid metabolism. This effect would be useful for medical treatment of non-operable glucagon secreting tumors.

Adenoma, Islet Cell↗
PubMed1984

Carbohydrate and lipid metabolism in cirrhosis. Evidence that hepatic uptake of gluconeogenic precursors and of free fatty acids depends on effective hepatic flow.

Splanchnic arteriovenous differences for several intermediary metabolites of carbohydrate and lipid metabolism were determined simultaneously with hepatic blood flow in seven normal subjects, eight patients with cirrhosis, and six patients with cirrhosis after surgical portosystemic shunt ( SPSS ) after an overnight fast. Arteriovenous differences in the legs were also determined together with flux measurement. The individual turnover rates of acetoacetate (AcAc) and 3 hydroxybutyrate (beta OHB) were also determined by means of isotopic techniques. Splanchnic gluconeogenic precursors and FFA uptakes were lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.05 and P less than 0.01, respectively). Splanchnic triglyceride output was also lower in cirrhotic patients with SPSS than in normal subjects (P less than 0.01), whereas no significant differences were found for AcAc, beta OHB, and glucose release. In the group of cirrhotic patients without SPSS , those patients with negligible signs of portal systemic shunt and normal splanchnic blood flow had uptake of gluconeogenic precursors and of FFA normal or higher than that of normal subjects, whereas those patients with signs of spontaneous portal systemic shunt behaved like cirrhotic patients with SPSS . Alanine release from the leg was lower in both cirrhotic patient groups. Tracer determined hepatic output of AcAc and beta OHB was higher in cirrhotic patients with SPSS (P less than 0.05). Plasma clearance rates of AcAc and beta OHB were significantly elevated in both cirrhotic patient groups. Close agreement was found between tracer and catheterization techniques in the evaluation of ketone body production in cirrhotic patients with SPSS , whereas in cirrhotic patients without SPSS tracer determined hepatic output was slightly lower, possibly because of extrahepatic splanchnic tissue ketone body uptake. In conclusion, our data in patients with cirrhosis indicate that: 1) splanchnic uptake of gluconeogenic precursors and of FFA was related to the degree of portal systemic shunt, e.g. to the degree of effective hepatic blood flow; 2) liver triglyceride but not ketone body output was decreased by the impaired FFA (and glycerol) liver uptake; 3) the higher circulating levels of gluconeogenic precursors (except alanine) and of FFA appeared at least partially due to lower hepatic removal of these metabolites; and 4) peripheral use of ketone bodies was increased and alanine release from the leg reduced in patients with cirrhosis.

Adult↗
PubMed1983

Effect of insulin replacement on intermediary metabolism in diabetes secondary to pancreatectomy.

Patients with diabetes due to pancreatectomy have metabolic features different from Type 1 (insulin-dependent) diabetes after insulin withdrawal. Whether or not glucagon by itself or combined glucagon-insulin absence are responsible for this metabolic behaviour is unknown. This study was carried out to evaluate the ability of insulin replacement to abolish differences between patients with Type 1 diabetes and patients with diabetes due to pancreatectomy. We studied the diurnal patterns of intermediary metabolites, free insulin, and glucagon using the Biostator (glucose-controlled insulin infusion system) and intensive subcutaneous insulin therapy in five patients after total pancreatectomy, five after partial pancreatectomy and seven patients with Type 1 diabetes. All were studied for 24 h after an overnight period of normoglycaemia. Insulin requirement was lower in the patients with total pancreatectomy than in patients with partial pancreatectomy or Type 1 diabetes during both types of insulin treatment (p less than 0.05). Blood glucose and free insulin were similar in all the groups in both conditions. Immunoreactive glucagon was higher in the patients with diabetes secondary to pancreatectomy than in Type 1 diabetic patients. However, glucagon levels did not increase after arginine infusion in the patients with total pancreatectomy, and column chromatography of blood samples from two totally pancreatectomized patients showed no significant levels of immunoreactive pancreatic glucagon. Non-esterified fatty acids and ketone bodies were similar during Biostator and intensive subcutaneous insulin therapy. By contrast, gluconeogenic precursors (lactate, pyruvate, alanine and glycerol) were higher in patients with total pancreatectomy than in patients with partial pancreatectomy and Type 1 diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Metabolic effects of moderate alcohol intake with meals in insulin-dependent diabetics controlled by artificial endocrine pancreas (AEP) and in normal subjects.

In order to evaluate the effects of moderate alcohol intake on intermediate metabolites, five normal subjects and five euglycemic insulin-dependent diabetics (IDDM) were administered two different isocaloric diets; in one diet 35% of the caloric intake consisted of red wine. The insulin-dependent diabetics were connected to an artificial endocrine pancreas (AEP), and glucose levels were continuously monitored. Blood lactate, pyruvate, acetoacetate (AcAc), 3-hydroxybutyrate (3-OHB), glycerol, free fatty acids (FFA), and alanine levels were measured over a 15-hour period from 9 AM to 12 PM. The results showed that alcohol intake did not significantly influence the glucose profiles in either group (111 +/- 4 mg/100 ml versus 110 +/- 4 mg/100 ml for IDDM; 72 +/- 2 mg/100 ml versus 82 +/- 3 mg/100 ml for controls, 15-hour mean +/- SEM), but in both groups it induced a marked increased in the levels of lactate (1.115 +/- 0.067 mM/liter with alcohol versus 0.706 +/- 0.031 mM/liter without alcohol for IDDM; 0.847 +/- 0.052 mM/liter with alcohol versus 0.666 +/- 0.035 mM/liter without alcohol for controls), in the lactate/pyruvate ratio (24.04 +/- 2.12 with alcohol versus 11.42 +/- 0.20 without alcohol for IDDM; 20.84 +/- 2.16 with alcohol versus 11.62 +/- 0.27 without alcohol for controls), in the levels of 3-OHB (0.081 +/- 0.007 mM/liter with alcohol versus 0.046 +/- 0.003 mM/liter without alcohol for IDDM; 0.067 +/- 0.007 mM/liter with alcohol versus 0.025 +/- 0.002 mM/liter without alcohol for controls) and in the 3-OHB/AcAc ratio (1.452 +/- 0.153 with alcohol versus 0.599 +/- 0.036 without alcohol for IDDM; 1.723 +/- 0.198 with alcohol versus 0.439 +/- 0.040 without alcohol for controls) because of a more reduced redox state. Alcohol intake during meals depressed alanine concentration, while glycerol levels showed a transient increase. Reduced blood FFA concentrations after alcohol intake were observed only in controls. This study demonstrates that moderate alcohol intake with meals also affects intermediate metabolites despite euglycemia. These effects were similar both in normal subjects and in IDDM, even if the harmful effects of alcohol may be enhanced by poor metabolic control in the latter.

Adult↗
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↗