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Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 235 records · Page 13Linked to original sources
PubMed1984

Adrenergic blockade alters glucose kinetics during exercise in insulin-dependent diabetics.

We investigated the effects of alpha and/or beta adrenergic blockade (with phentolamine and/or propranolol) on glucose homeostasis during exercise in six normal subjects and in seven Type I diabetic subjects. The diabetics received a low dose insulin infusion (0.07 mU/kg X min) designed to maintain plasma glucose at approximately 150 mg/dl. In normals, neither alpha, beta, nor combined alpha and beta adrenergic blockade altered glucose production, glucose uptake, or plasma glucose concentration during exercise. In diabetics, exercise alone produced a decline in glucose concentration from 144 to 116 mg/dl. This was due to a slightly diminished rise in hepatic glucose production in association with a normal increase in glucose uptake. When exercise was performed during beta adrenergic blockade, the decline in plasma glucose was accentuated. An exogenous glucose infusion (2.58 mg/kg X min) was required to prevent glucose levels from falling below 90 mg/dl. The effect of beta blockade was accounted for by a blunted rise in hepatic glucose production and an augmented rise in glucose utilization. These alterations were unrelated to changes in plasma insulin and glucagon levels, which were similar in the presence and absence of propranolol. In contrast, when the diabetics exercised during alpha adrenergic blockade, plasma glucose concentration rose from 150 to 164 mg/dl. This was due to a significant increase in hepatic glucose production and a small decline in exercise-induced glucose utilization. These alterations also could not be explained by differences in insulin and glucagon levels. We conclude that the glucose homeostatic response to exercise in insulin-dependent diabetics, in contrast to healthy controls, is critically dependent on the adrenergic nervous system.

Adult↗
PubMed1984

Mechanism of improvement in glucose metabolism after chronic glyburide therapy.

The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P less than 0.01) without change in fasting insulin levels. Basal hepatic glucose production (HGP) was slightly elevated in NIDDM versus controls (2.35 versus 2.18 mg/kg X min, P = NS) and was positively correlated with the fasting glucose concentration (r = 0.93, P less than 0.001). With chronic glyburide therapy, HGP declined to 1.72 mg/kg X min (P less than 0.01 versus preglyburide) and remained highly correlated with the fasting glucose concentration (r = 0.85, P less than 0.005). Basal glucose clearance in NIDDM was reduced by 48% compared with age-matched controls (1.22 versus 2.32 ml/kg X min, P less than 0.001) and was unchanged after 3 mo of glyburide. Thus, the most important factor responsible for the decline in fasting plasma glucose concentration was an inhibition of hepatic glucose output. The decrease in basal hepatic glucose production and fasting plasma glucose concentration occurred without any change in fasting plasma insulin or C-peptide concentration. Insulin-mediated glucose metabolism (insulin clamp technique) was reduced by 55% in NIDDM (2.91 versus 6.39 mg/kg X min, P less than 0.001). After glyburide, insulin-mediated glucose metabolism increased by 26% to 3.67 mg/kg X min (P less than 0.01). This increase in tissue sensitivity to insulin was unassociated with any change in insulin binding to monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1983

Splanchnic and renal metabolism of insulin in human subjects: a dose-response study.

Kinetic analyses of insulin metabolism were performed in 32 healthy subjects with hepatic-venous or renal-venous catheters, in whom steady-state conditions of hyperinsulinemia or hyperglycemia were achieved with the use of the glucose-insulin clamp technique. In the basal state, the splanchnic bed removed 42 +/- 2% of the insulin influx. After graded insulin infusions with maintenance of euglycemia, stable arterial insulin levels of 35-1,430 microU/ml were attained. Splanchnic insulin extraction was constant (approximately 60%) at physiological insulin levels but fell (to 29 +/- 1%, P less than 0.02) at supraphysiological (greater than 500 microU/ml) concentrations. The metabolic clearance rate of infused insulin was essentially constant within the physiological concentration range. Hyperglycemia (+125 mg/100 ml) did not alter splanchnic insulin extraction. Basally, the kidneys extracted 0.04 +/- 0.01 mU X min-1 X kg-1 or 25 +/- 5% of arterial insulin. Renal insulin clearance (3.9 +/- 0.4 ml X min-1 X kg-1) represented over 80% of the extrasplanchnic insulin clearance. Hyperglycemia (+125 mg/100 ml) had no effect on renal insulin extraction. In conclusion, a) both splanchnic and renal insulin removal are independent of glycemia and increase in proportion to plasma insulin concentration within the physiological range; b) splanchnic uptake is the dominant mechanism of removal of insulin from the circulation whether the route of delivery is portal or peripheral; and c) the kidneys account for the greater part of extrasplanchnic insulin metabolism.

Adult↗
PubMed1983

Postpericardiectomy syndrome in a patient with radiation-induced pericardial effusion.

A 30-year-old man with mild exertional dyspnea of recent (2 months) onset was found to have a massive pericardial effusion. The patient had received mediastinal irradiation for Hodgkin's disease over 9 years previously. No evidence of recurrent lymphoma or other causes of pericarditis could be found. Following subtotal pericardiectomy, the patient developed a syndrome characterized by precordial discomfort, low-grade fever, tachycardia, and friction rubs. The electrocardiogram, normal preoperatively, showed diffusely negative T waves. Antimyocardial antibodies appeared in the serum. The syndrome, a hitherto unrecognized sequela of pericardiectomy, is interpreted as a mediastinoepicarditis, of possibly autoimmune origin.

Adult↗
PubMed1983

Acute respiratory distress syndrome in an adult patient with a myelodysplastic disorder.

A 58-year-old man was diagnosed to have refractory anaemia with excessive blasts. After 3 1/2 years of relative control on periodic blood transfusions, the patient developed an acute leukaemia. Although the blastic crisis was not extreme (WBC counts less than 100 X 10(9)/l), a severe, intractable respiratory distress syndrome set in and brought the patient to the exitus in a few days. Overt signs of septic shock were absent, as was evidence of any other known cause of adult respiratory distress. Acute pulmonary failure can be the cause of death in leukaemic patients even in the absence of overwhelming sepsis or hyperleucocytosis.

Acute Disease↗
PubMed1983

Effect of fatty acids on glucose production and utilization in man.

Since the initial proposal of the glucose fatty acid cycle, considerable controversy has arisen concerning its physiologic significance in vivo. In the present study, we examined the effect of acute, physiologic elevations of FFA concentrations on glucose production and uptake in normal subjects under three controlled experimental conditions. In group A, plasma insulin levels were raised and maintained at approximately 100 microU/ml above base line by an insulin infusion, while holding plasma glucose at the fasting level by a variable glucose infusion. In group B, plasma glucose concentration was raised by 125 mg/100 ml and plasma insulin was clamped at approximately 50 microU/ml by a combined infusion of somatostatin and insulin. In group C, plasma glucose was raised by 200 mg/100 ml above the fasting level, while insulin secretion was inhibited with somatostatin and peripheral glucagon levels were replaced with a glucagon infusion (1 ng/min X kg). Each protocol was repeated in the same subject in combination with a lipid-heparin infusion designed to raise plasma FFA levels by 1.5-2.0 mumol/ml. With euglycemic hyperinsulinemia (study A), lipid infusion caused a significant inhibition of total glucose uptake (6.3 +/- 1.3 vs. 7.4 +/- 0.6 mg/min X kg, P less than 0.02). Endogenous glucose production (estimated by the [3-3H]glucose technique) was completely suppressed both with and without lipid infusion. With hyperglycemic hyperinsulinemia (study B), lipid infusion also induced a marked impairment in glucose utilization (6.2 +/- 1.1 vs. 9.8 +/- 1.9 mg/min X kg, P less than 0.05); endogenous glucose production was again completely inhibited despite the increase in FFA concentrations. Under both conditions (A and B), the percentage inhibition of glucose uptake by FFA was positively correlated with the total rate of glucose uptake (r = 0.69, P less than 0.01). In contrast, when hyperglycemia was associated with relative insulinopenia and hyperglucagonemia (study C), thus simulating a diabetic state, lipid infusion had no effect on glucose uptake (2.9 +/- 0.2 vs. 2.6 +/- 0.2 mg/min X kg) but markedly stimulated endogenous glucose production (1.4 +/- 0.5 vs. 0.5 +/- 0.4 mg/min X kg, P less than 0.005). Under the same conditions as study C, a glycerol infusion producing plasma glycerol levels similar to those achieved with lipid-heparin, enhanced endogenous glucose production (1.5 +/- 0.5 vs. 0.7 +/- 0.6 mg/min X kg, P less than 0.05). We conclude that, in the well-insulinized state raised FFA levels effectively compete with glucose for uptake by peripheral tissues, regardless of the presence of hyperglycemia. When insulin is deficient, on the other hand, elevated rates of lipolysis may contribute to hyperglycemia not by competition for fuel utilization, but through an enhancement of endogenous glucose output.

3-Hydroxybutyric Acid↗
PubMed1983

Splanchnic and peripheral disposal of oral glucose in man.

Oral glucose (92 g) was administered to 22 healthy, young volunteers undergoing hepatic vein catheterization, and net splanchnic glucose output (SGO) was measured during the basal period and for 4 h after glucose ingestion. In the basal state, SGO averaged 1.90 +/- 0.11 mg/min X kg. After glucose, SGO rose to a peak value of 6.65 +/- 0.83 mg/min X kg at 30 min and returned to baseline by 3 h. Total SGO over 4 h was 69 +/- 4 g; assuming complete absorption of the load, this amount represented 75% of the oral glucose. In a subgroup of six subjects, leg glucose uptake was simultaneously quantitated by femoral vein catheterization and leg blood flow measurement. In the postabsorptive state, glucose uptake by one leg was 24 +/- 8 mg/min and increased to a mean value of 76 +/- 7 mg/min during the 4 h after glucose ingestion. Overall, 18 +/- 2 g/4 h of glucose were taken up by one leg, which extrapolates to a total body muscle uptake of 65 +/- 4 g over 4 h. We conclude that in normal man, well over 2/3 of an oral glucose load escapes splanchnic removal, and that the peripheral tissues quantitatively play the dominant role in glucose disposal.

Adult↗
PubMed1982

Hepatic and peripheral insulin resistance: a common feature of type 2 (non-insulin-dependent) and type 1 (insulin-dependent) diabetes mellitus.

Hepatic glucose production (3H-glucose technique) and insulin-mediated glucose uptake (insulin clamp technique) were measured in 38 Type 2 (non-insulin-dependent) and 11 Type 1 (insulin-dependent) diabetic patients. Fasting plasma glucose concentration was 8.3 +/- 0.5 mmol/l in the former, and 9.6 +/- 1.3 mmol/l in the latter group; the respective fasting plasma insulin levels were 19 +/- 2 mU/l (p less than 0.005 versus 13 +/- 1 mU/l in 33 age-matched control subjects), and 9 +/- mU/l (p less than 0.01 versus 14 +/- 1 mU/l in 36 younger control subjects). In the fasting state, hepatic glucose production was slightly increased (15%, 0.1 greater than p greater than 0.05) in the Type 2 diabetic patients and markedly elevated (65%, p less than 0.001) in the Type 1 patients compared with their respective control groups. In both groups of diabetic subjects, the rates of hepatic glucose production were inappropriately high for the prevailing plasma glucose and insulin levels, indicating the presence of hepatic resistance to insulin. Basal plasma glucose clearance was also significantly reduced in both the Type 2 (34%) and the Type 1 (14%) diabetic subjects. The fasting plasma glucose concentration correlated directly with hepatic glucose production, and inversely with plasma glucose clearance. During the insulin clamp, plasma insulin was maintained at approximately 100 mU/l in all groups, while plasma glucose was maintained constant at the respective fasting levels. Total glucose uptake was reduced in both the Type 2 (4.57 +/- 0.31 versus 6.39 +/- 0.25 mg . min -1 . kg -1 in the control subjects, p less than 0.01) and the Type 1 (4.77 +/- 0.48 versus 7.03 +/- 0.22 mg . min -1 . kg -1, p less than 0.01)diabetic patients. Insulin-stimulated glucose clearance was reduced to a similar extent in Type 2 (54%) and Type 1 (61%) diabetic subjects, and correlated directly with fasting glucose clearance. These results show that insulin resistance is a common feature of both types of diabetes and can be demonstrated in the basal as well as the insulin-stimulated state. Both hepatic and peripheral resistance to the action of insulin contribute to diabetic hyperglycaemia.

Adult↗
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

Effect of bicycle exercise on insulin absorption and subcutaneous blood flow in the normal subject.

Elimination of 8 units 125I-insulin and 99mTc-pertechnetate from a subcutaneous depot on the thigh or the abdomen was studied at rest and during intense bicycle exercise in healthy postabsorptive volunteers. Disappearance rates of the tracers as well as plasma insulin and glucose concentrations were determined before, during and after the 20 min exercise period, and compared to corresponding values obtained during a non-exercise, control study on another day. Leg exercise caused a two-fold increase in the rate of 125I-insulin disappearance from a leg depot (first-order rate constants rose from 0.68 +/- 0.15 to 1.12 +/- 0.12% . min-1, P less than 0.05), but had no significant effect on the rate of disappearance from an abdominal depot (rate constants were 0.75 +/- 0.17 and 0.87 +/- 0.18% . min-1 at rest and during exercise, respectively). 99mTC-pertechnetate clearance from leg or abdomen showed no significant change during exercise, indicating that subcutaneous blood flow was unaltered. Leg, but not abdominal, injection of insulin was associated with a greater rise in plasma insulin during exercise than at rest. The average difference between exercise and control insulin area-under-curve in the leg group (1426 +/- 594% . min) was significantly greater (P less than 0.05) than that from the abdominal group (298 +/- 251% . min). When the data from the two study groups were pooled, a direct relationship was found to exist between the change in 125I-insulin disappearance rate and the change in plasma insulin concentration (r = 0.61, P less than 0.02). Plasma glucose levels fell throughout the observation period both during the exercise and the control study, following leg as well as abdominal injection. The glucose decremental area was greater during exercise than at rest both following leg (P less than 0.05) and abdominal injection (P less than 0.01). The exercise-induced mean reduction in plasma glucose was 60% lower following abdominal injection, but this difference was not significant. In conclusion, the present results demonstrate that, in healthy subjects in the postabsorptive state (a) intense physical exercise of short duration can accelerate the absorption of subcutaneously injected insulin; (b) the effect is more pronounced at injection sites near the exercising parts; (c) an increase in subcutaneous blood flow is not the main reason for this effect.

Adult↗
PubMed1982

Transient hepatic response to glucagon in man: role of insulin and hyperglycemia.

We infused glucagon into normal humans while preventing changes in plasma glucose and insulin. Insulin (0.45 mU . min-1 . kg-1) were infused for 90 min, while euglycemia was maintained by a variable glucose infusion. Subsequently, glucagon (6 ng . min-1 . kg-1) was added, and changes in plasma glucose were avoided by appropriately reducing the glucose infusion. With insulin alone, glucose production (GP) fell to zero. When hyperglucagonemia (530 +/- 32 pg/ml) was superimposed, GP rose promptly and then slowly declined. However, between 180 and 240 min, GP remained elevated (1.72 +/- 0.30 mg . min-1 . kg-1) as compared to an insulin control study (0.03 +/- 0.20, P less than 0.025). When hyperglycemia (+25 mg/100 ml) was induced between 180 and 240 min, glucagon-stimulated GP was completely suppressed. To determine whether this effect was mediated by hyperglycemia per se or glucose-induced hyperinsulinemia, between 180 and 240 min we increased either a) the insulin infusion (by 0.25 mU . min-1 . kg-1) while maintaining euglycemia or b) plasma glucose (+25 mg/100 ml) while blocking insulin release with somatostatin. When the insulin was increased, GP declined by 68 +/- 13% (P less than 0.02). When plasma glucose alone was raised, GP fell from 1.44 +/- 0.09 to 0.07 +/- 0.16 mg . min-1 . kg-1 (less than 0.002). In conclusion, the hepatic response to sustained hyperglucagonemia is more persistent if changes in plasma glucose are prevented, and its transient nature is in part explained by a feedback adjustment to glucagon-induced hyperglycemia and hyperinsulinemia.

Adult↗
PubMed1982

Schwartz-Jampel syndrome with autosomal-dominant inheritance.

A 4-year follow-up study of 2 brothers affected by Schwartz-Jampel syndrome is reported. The children, aged 16 and 7 years, respectively, showed the clinical and electromyographical signs of the disorder. Further investigation showed some typical facial features of the syndrome, percussion myotonia and abnormal EMG pattern characterized by continuous muscle activity at rest in 3 other members of the same family. On the basis of our data, we suggest that inheritance of the Schwartz-Jampel syndrome may not only be recessive, as reported by most authors, but also dominant, with a different clinical expression.

Abnormalities, Multiple↗