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Biomedical subjects

M C Foss

Publications and source records attributed to M C Foss.

At least 55 records · Page 3Linked to original sources

Serum levels of tumor necrosis factor in insulin-dependent diabetic patients.

We determined the serum concentrations of tumor necrosis factor (TNF) in 15 nondiabetic healthy subjects and in 36 insulin-dependent (type I) diabetic outpatients. The mean (+/- SD) annual fasting plasma glucose, urine glucose and HbA1 levels of the diabetic group were 179 +/- 71 mg/dl, 13.0 +/- 13.2 g/day and 12.3 +/- 1.3%, respectively. The mean serum TNF concentration measured by immunoradiometric assay of the diabetic group (8.6 +/- 1.9 pg/ml) was significantly higher than healthy controls (6.9 +/- 0.9 pg/ml). Within the diabetic group, there was no correlation between serum TNF levels and either duration of diabetes or indices of metabolic control. However, serum TNF levels progressively increased from the well to the poorly controlled diabetic groups: 8.1 +/- 1.5 (G), 8.2 +/- 1.4 (F) and 9.4 +/- 2.4 (P) pg/ml, respectively, which parallel levels of HbA1 (%): 8.4 +/- 2.4, 11.7 +/- 1.8 and 14.6 +/- 1.2, respectively. Serum TNF levels of the diabetic patients with chronic complications (N = 7, 9.5 +/- 2.3 pg/ml) and without complications (N = 29, 8.4 +/- 1.7 pg/ml) were statistically higher than control subjects. The progressive increase of the serum TNF levels from the well to the poorly controlled diabetic groups suggests a relationship between levels of this cytokine and protein glycosylation.

Adolescent↗

Hormonal and metabolic study of a case of adiposis dolorosa (Dercum's disease).

A case of a 43-year-old nonobese woman with adiposis dolorosa (Dercum's disease) is reported. Muscle glucose uptake and oxidation before and after ingestion of 75 g of glucose were similar to control group values, although a greater insulin release (16,578 vs 6,242 +/- 1,136 microU/3 h) occurred simultaneously. In vitro studies of abdominal normal and painful subcutaneous adipose tissue of the patient revealed lower responsiveness to norepinephrine and lack of response to the antilipolytic effect of insulin in the painful adipose tissue (0.98 vs 1.43 microM FFA/10(6) cells at 5.0 microM of norepinephrine). The disease was not correlated with the HLA system and there were no alterations in hormonal secretion at the pituitary, adrenal, gonadal, and thyroid levels. These findings indicate the presence of peripheral insulin resistance in this patient with adiposis dolorosa.

Adipose Tissue↗

Peripheral glucose metabolism in acromegaly.

The present study was designed to determine the effect of chronic GH excess on forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Nine normal subjects and 10 nondiabetic acromegalic patients (5 of them with normal glucose tolerance) were studied after an overnight fast (12-14 h) and for 3 h after the ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Decreased forearm glucose uptake was observed in the acromegalic patients compared to that in the normal subjects (380 +/- 84 vs. 709 +/- 56 mumol/100 mL forearm.3 h) with diminished nonoxidative glucose metabolism (262 +/- 81 vs. 572 +/- 53 mumol/100 mL forearm.3 h). The acromegalics with normal glucose tolerance also showed decreased forearm glucose uptake and nonoxidative glucose metabolism compared to normal subjects (271 +/- 124 vs. 709 +/- 56 and 133 +/- 110 vs. 572 +/- 53 mumol/100 mL forearm.3 h, respectively). Muscle glucose oxidation did not differ significantly in normal subjects, the entire group of acromegalic patients, and the acromegalics with normal glucose tolerance (137 +/- 18 vs. 118 +/- 22 vs. 138 +/- 34 mumol/100 mL forearm.3 h, respectively). Serum FFA levels and lipid oxidation rates were similar in the normal subjects and the acromegalic patients, and declined in a similar fashion after glucose ingestion. Insulin levels were significantly higher in acromegalic patients than in normal subjects before and after glucose loading. In conclusion, this study showed that the insulin resistance occurring in the presence of chronic GH excess is accompanied by impaired muscle glucose uptake and nonoxidative glucose metabolism, which are early derangements because they are also observed in acromegalic patients with normal glucose tolerance.

Acromegaly↗

Peripheral glucose and potassium transport after glucose ingestion in normal subjects.

This study was designed to quantify forearm potassium uptake or release in the postabsorptive state and after an oral glucose challenge, and if there is association of potassium uptake with glucose and free fatty acids (FFA) metabolism in peripheral tissues of normal subjects. Nine healthy volunteers (4M and 5F) were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. The forearm glucose uptake rate reached the maximum at 60 minutes (0.985 mg/100 ml forearm.min), declining to the basal levels at the end of the 3 h of study. Although heterogeneously in the postabsorptive state, potassium moves out of the forearm muscle into the venous blood in normal individuals. After glucose ingestion, the potassium release diminished and there was also potassium uptake during the last hour of the study. The arterial FFA levels decreased significantly after the glucose load. In conclusion, the results of this study showed that in peripheral tissues: 1) during the first 2 h after the ingestion of 75 g of glucose there was a reduction in potassium release; 2) potassium uptake only occurred in the last hour when insulin levels were slightly higher, plasma glucose were similar and FFA were lower than in the postabsorptive period; 3) there was a clear dissociation between potassium and glucose uptake.

Adolescent↗

Peripheral glucose metabolism in human hyperthyroidism.

The present study was designed to determine the effect of spontaneous hyperthyroidism on the forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge. Ten normal subjects and 11 hyperthyroid patients were studied after an overnight fast (12-14 h) and for 3 h after ingestion of 75 g glucose. Peripheral glucose metabolism was analyzed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry. Increased forearm glucose uptake was observed in the hyperthyroid patients compared to that in the normal subjects (1286 +/- 212 vs. 677 +/- 88 mumol/100 mL forearm.3 h) with enhanced glucose oxidation (443 +/- 40 vs. 147 +/- 29 mumol/100 mL forearm.3 h). Nonoxidative glucose metabolism was also greater in hyperthyroid patients than in normal subjects (842 +/- 234 vs. 529 +/- 90 mumol/100 mL forearm.3 h). Basal serum FFA levels were significantly higher in hyperthyroid than in normal subjects (0.252 +/- 0.025 vs. 0.182 +/- 0.022 g/L), as were the basal lipid oxidation rates in the forearm muscles of the thyrotoxic individuals (0.290 +/- 0.066 vs. 0.088 +/- 0.016 mg/100 mL forearm.min). After glucose ingestion, serum FFA levels and lipid oxidation rates declined significantly to equivalent values in both groups of subjects, and the similar basal insulin concentrations increased to significantly higher levels in the hyperthyroid patients. In conclusion, spontaneous human hyperthyroidism increases glucose uptake by the forearm muscles in the postabsorptive state and during an oral glucose challenge, with augmented fluxes of glucose through the oxidative and nonoxidative pathways.

Administration, Oral↗

Association of specific histocompatibility antigens and acanthosis nigricans with insulin resistance.

1. The association or interaction of histocompatibility antigens (HLA) and acanthosis nigricans with type A insulin resistance was studied in 13 patients (10 from family I, 2 from family II and an isolated case) for both sexes. 2. HLA typing for the A, B, C and D antigens was performed by a standard microcytotoxicity test for all patients and for 100 normal controls from the same geographic area. 3. The frequency of HLA B8 was 21% in the control group and 100% in patients with acanthosis nigricans. The frequency of HLA A1B8 was 15% in controls and 73% in acanthotic patients. 4. All the members of family I presenting the association of a possible insulin receptor defect (most likely provided by patient 2) with HLA B8 (provided by patient 1) showed a more pronounced clinical and laboratory expression of insulin resistance. 5. These data suggest that class I antigens of major histocompatibility complex (MHC), A1 and/or B8, may be involved in the pathogenesis of some forms of insulin resistance such as acanthosis nigricans (type A syndrome), possibly by a molecular interaction of the antigens with insulin receptors.

Acanthosis Nigricans↗

Endogenous hyperinsulinemia and release of growth hormone following a glucose load as well as in response to thyrotropin releasing hormone in acromegaly.

This study was designed to determine the relationship between endogenous hyperinsulinemia or free fatty acid (FFA) levels and the abnormal release of growth hormone (GH) during the oral glucose tolerance test (OGTT) or in response to thyrotropin releasing hormone (TRH) in acromegalic patients. Seventeen patients with acromegaly and nine healthy control subjects were studied. The 12 acromegalic patients who did not show the paradoxical response of increased GH secretion to the OGTT and/or to TRH exhibited higher insulin levels (total area under the curve during the OGTT) than patients who did. However, the FFA levels of the groups of acromegalic patients were similar. These data suggest that the endogenous hyperinsulinemia exhibited by many patients with acromegaly is associated with the absence of the paradoxical increase in GH secretion during the OGTT and/or after TRH.

Acromegaly↗

Effect of oral glucose on peripheral muscle fuel metabolism in fasted men.

1. The metabolic adaptations of peripheral muscle during a 5-day "modified" fast (daily oral intake of 200 g of glucose) were studied in 12 normal males. The volunteers were studied initially after receiving a balanced 2,400-kcal diet for at least 3 days (S1) and then after 5 days of modified fast (S2). The forearm muscle exchange of energy substrate (glucose) and the carbohydrate and lipid oxidation rates in muscle were measured during the postabsorptive state (S1) and after an oral glucose challenge (S2). 2. Glucose intolerance was not observed in either situation. Arterial glucose levels increased from a basal value of 83 mg/100 ml to 171 mg/100 ml in S1 and to 187 mg/100 ml in S2 at 30 and 60 min, respectively, and returned to basal values at 180 min in both studies. Increased forearm glucose uptake was observed in S2 compared to S1 (121.7 +/- 17.1 vs 92.6 +/- 12.0 mg 100 ml forearm-1 3 h-1), with decreased glucose oxidation (23.8 +/- 3.7 vs 30.4 +/- 4.7 mg 100 ml forearm-1 3 h-1) and increased glucose storage (98.0 +/- 16.6 vs 62.2 +/- 10.8 mg 100 ml forearm-1 3 h-1) as muscle glycogen. 3. Basal serum free fatty acid (FFA) levels were significantly more elevated in S2 than S1 (1030 +/- 95 vs 657 +/- 59 mumol/l; P less than 0.05) but were markedly reduced by glucose ingestion in both studies (352 +/- 33 (S2) vs 364 +/- 30 (S1) mumol/l at 120 min). Basal FFA oxidation was similar in both studies (0.091 +/- 0.015 (S1) vs 0.105 +/- 0.019 (S2) mg 100 ml forearm-1 min-1) and decreased significantly 3 h after glucose ingestion only in S1 (0.030 +/- 0.010 (S1) vs 0.078 +/- 0.020 (S2) mg 100 ml forearm-1 min-1; P less than 0.05). 4. The insulin response to oral glucose was similar in both studies (11,060 +/- 899 (S1) vs 11,078 +/- 918 (S2) microU ml-1 3 h-1), but the peak concentration occurred later (60 min (S2) vs 30 min (S1] and basal levels were significantly lower in S2 compared to S1 (9.2 +/- 1.7 vs 11.1 +/- 1.5 microU/ml; P less than 0.05). 5. These data show that the metabolic adaptations of normal subjects to a 5-day "modified" fast (daily oral intake of 200 g glucose) were increased muscle uptake of glucose, with reduced glucose oxidation and increased glucose storage in the form of muscle glycogen.

Fasting↗

Replacement rate of free fatty acids in fasted rats adapted to a high-protein diet.

1. Free fatty acid (FFA) mobilization during fasting was measured in cats fed a meat diet (63% protein, 18% fat, 6% carbohydrate, w/w) or a carbohydrate-rich diet (15% protein, 10% fat, 70% carbohydrate), and in rats adapted to a high-protein, carbohydrate-free synthetic diet (70% casein, 8% fat) or a balanced synthetic diet (66% carbohydrate, 17% casein, 8% fat). 2. Fasted cats and rats on the high-protein diet showed reduced rates of plasma FFA increase. Their blood glucose was unchanged but higher than that of controls fed a carbohydrate-rich diet after fasting for 24 (rats) or 48 h (cats). 3. The steady-state rate of plasma FFA replacement was determined with 1-[14C]-palmitate in fed and fasted rats with plasma FFA levels ranging from 0.30 to 1.45 mumol/ml adapted to the high-protein or to the balanced diet. Under these dietary conditions, the FFA replacement rates were linearly related to the concentration of plasma FFA. However, the slope of the regression line was steeper for the rats on the high-protein diet. Thus, for the same concentration of plasma FFA, replacement rates for rats adapted to the high-protein diet were higher than for controls. 4. These data indicate that the higher rates of FFA replacement required in situations demanding an increased supply of FFA for animals on high-protein regimens are attained with smaller increases in plasma FFA concentration.

Animals↗

Peripheral muscle glucose and potassium transport in a family with acanthosis nigricans and insulin resistance.

This study was designed to determine the forearm exchange of glucose and potassium in four members of a family exhibiting acanthosis nigricans and insulin resistance. Total areas under the curves for potassium release or uptake were within the normal range in all patients. Peripheral glucose uptake, however, was normal in 3 patients and lower in one patient. In the latter patient, the dissociation observed between glucose and potassium transport suggests several manners of differential impairment of insulin action and/or steps distal to the insulin receptor as being responsible for insulin resistance.

Acanthosis Nigricans↗

Carbohydrate, lipid and amino acid metabolism of insulin-dependent diabetic patients regulated by an artificial beta-cell unit.

To characterize the effects of artificial beta-cell directed insulin therapy on carbohydrate, lipid and amino acid metabolism, five insulin-dependent diabetic patients were challenged with a 100-g glucose meal while on conventional (single or split mixed insulin injections) therapy and again after 72 hr on an artificial beta-cell unit. It was verified that the high levels of blood glucose of the conventionally treated diabetics were marked reduced toward normal by the artificial beta-cell therapy, while the blood lactate and pyruvate concentrations increased significantly to levels higher than in normal controls. The elevated levels of FFA, glycerol, and ketones in the diabetics under conventional therapy were entirely normalized during the artificial beta-cell regulation. Furthermore, the artificial beta-cell insulin therapy showed capable to restore the abnormalities in the blood profiles of alanine, glutamine and branched-chain amino acids, exceeding in some points the normal response. It was also detected hyperinsulinemia in the diabetics treated with the artificial beta-cell unit and no change in the pancreatic beta-cell function during this period of regulation, evidenced by low and unchanged blood levels of C-peptide. Marked suppression of pancreatic alpha-cell secretion was detected by the significant decrease of the hyperglucagonemia in the conventionally treated diabetics by the artificial beta-cell therapy. These studies reveal that the artificial beta-cell insulin therapy is capable of restoring to normal not only the abnormal glucose metabolism of conventionally treated diabetics, but also other substrate metabolism related to the lipid and protein homeostasis of the organism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of low-dose naloxone infusion on plasma ACTH and LH in patients with Cushing's and Addison's diseases.

The ACTH, cortisol and LH responses to low dose (0.8 mg/h) naloxone 90 min infusion were investigated in seven patients with untreated Cushing's disease, six patients with Addison's disease and four control subjects. Naloxone had no effects on ACTH hypersecretion or normal ACTH levels. These data confirm that naloxone cannot provide additional diagnostic or therapeutic approaches in ACTH hypersecretion syndromes, mainly in Cushing's disease. The mean percentage LH levels did not significantly change during low dose naloxone in controls or patients with Cushing's and Addison's diseases. This suggests that increased endogenous opioid peptides in these diseases may not modify the LH responses to low dose of naloxone. However, since three of five adults with Cushing's disease had increased LH levels during naloxone, further studies may be indicated.

Addison Disease↗

Effects of glucose loads of 50 and 100 g on carbohydrate and lipid oxidation in normal human subjects.

1. The effects of 50- and 100-g glucose loads on carbohydrate and lipid oxidation and substrate metabolism of seven normal subjects were studied in the postabsorptive state and for 3 h following glucose ingestion. 2. The increases in the non-protein respiratory quotient (npRQ) and carbohydrate oxidation rate were larger after the ingestion of 100 g glucose than after the 50-g glucose load. The total amount of glucose oxidized during the test with 100 g of glucose ingested orally (100-g OGT) (13.4 +/- 0.8 g/m2) was significantly greater than that oxidized during the 50-g OGT (9.5 +/- 0.6 g/m2), whereas lipid oxidation predominated in the tests with the smaller dose of glucose. The difference between the amounts of glucose oxidized during the two tests was greater when the increments above the basal values of glucose oxidation were compared (100-g OGT = 8.0 +/- 0.5 g/m2 vs 50-g OGT = 3.8 +/- 0.5 g/m2; P less than 0.001). 3. The glucose disposal data revealed that the subjects not only oxidized more of the hexose after the ingestion of 100 g of glucose but they also stored more than after the 50-g glucose meal. 4. The changes in the concentrations of glucose, lactate, pyruvate, alanine and insulin in the blood were also related to the amount of the glucose load. 5. It is suggested that the modulation of this oxidative response to glucose ingestion occurs in the insulin-dependent tissues.

Adult↗

Frequency of HLA antigens in a Brazilian type I diabetic population.

1. Sixty-five Brazilian, patients with type I, insulin-dependent diabetes mellitus (IDDM) and 100 unaffected individuals were typed for HLA-A, -B, -C and DR antigens. 2. A significantly higher frequency of HLA-A2 (48% of the patients versus 21% of the controls), B15 (20% of the controls), DR3 (57% of the patients versus 28% of the controls) and DR4 (54% of the patients versus 23% of the controls) was found for IDDM patients compared to the controls. 3. In contrast, DR2 (11% of the patients versus 31% of the controls) and DR7 (3% of the patients versus 21% of the controls) were lower in diabetics, but the difference was not significant. 4. The data reported here, when compared with those of other studies, emphasize the ethnic variability in HLA-IDDM associations.

Brazil↗

Effect of adrenalectomy on glucose homeostasis in rats fed a high-protein, carbohydrate-free diet.

1. The effect of adrenalectomy on the adjustments of carbohydrate metabolism to fasting was studied in rats fed a high-protein, carbohydrate-free (HP) diet. 2. Fasting for 24 h induced a 20% decrease of blood glucose levels in intact rats on the balanced, control (C) diet, but did not affect the blood glucose levels of rats adapted to the HP diet. After adrenalectomy, HP rats lost their capacity to maintain constant blood glucose levels during fasting, but the reduction in blood glucose (30% after 24 h) took longer to appear and was 50% smaller than in adrenalectomized C-rats. 3. Intact rats on the control diet responded to fasting with increased in vitro hepatic gluconeogenic capacity as well as increased phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase activities. Adrenalectomized C-rats also responded to fasting with increased gluconeogenesis and PEPCK activity. In contrast, for both intact and adrenalectomized HP-fed rats, liver gluconeogenesis and PEPCK activity, which were already high in the fed state, did not change or even decreased slightly after fasting. 4. After food restriction, the rates of glucose replacement by adrenalectomized rats on the control diet were higher than those of intact animals on the same diet. This effect was not observed in HP-fed rats, in which the rates of glucose replacement were even slightly lower in adrenalectomized than in intact animals. 5. These data suggest that the mechanism of fasting-induced hypoglycemia after adrenal removal is different for HP and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Liver trophism in dogs made diabetic by total pancreatectomy or alloxan administration.

1. In order to evaluate hepatic trophism in diabetic dogs, an experimental study was carried out on 30 adult mongrel dogs of both sexes weighing 11.9 +/- 1.6 kg, divided into three groups: 1) Controls (C) (N = 10), submitted to partial (30%) hepatectomy; 2) PD Animals (N = 10), submitted to partial hepatectomy plus total pancreatectomy with preservation of the duodenum during the same surgical intervention; 3) and AD Animals (N = 10), submitted to partial and simultaneously made diabetic with alloxan. 2. The animals were submitted to an oral glucose tolerance test (OGTT) one day before and on the 7th day after partial hepatectomy to evaluate the severity of diabetes. During the post-hepatectomy period the fasting glycemia values were similar for both diabetic groups (greater than 200 mg%). During OGTT, blood glucose levels of the diabetic groups peaked at 60 min but were significantly higher for the AD than for the PD group. The difference persisted at 120 and 180 min, but was no longer statistically significant. 3. Liver trophism was evaluated by measuring liver RNA content and the nuclear volume of hepatocytes. Both diabetic groups showed significantly lower RNA contents and absence of nuclear hypertrophy compared to partially hepatectomized controls probably because of the severe diabetes induced in these animals.

Alloxan↗

Lipolysis and the antilipolytic effect of insulin in adipocytes from rats adapted to a high-protein diet.

Free fatty acid (FFA) mobilization during fasting was investigated in rats fed a high-protein, carbohydrate-free (HP) diet (70% casein, 8% fat, wt/wt) or a balanced diet (66% carbohydrate, 17% casein, 8% fat) for 30 to 40 days. In vivo, rats on the HP diet showed reduced rates of plasma FFA increase during fasting. Their blood sugar remained unchanged and was higher than that of control rats 24 hours after removal of food. In the fed state, serum insulin levels were smaller in HP-fed rats but did not differ significantly in the two experimental groups during fasting. In vitro, the rates of glycerol and FFA release by epididymal fat pads obtained from fasted rats were similar in rats consuming the HP diet. Fat cells isolated from rats on the HP diet also had reduced rates of basal lipolysis. Furthermore, they showed a significant increase in responsiveness to the lipolytic action of noradrenaline and an increase in both sensitivity and responsiveness to the inhibitory effect of insulin on noradrenaline-stimulated lipolysis. Adipocytes from HP-fed and control rats had mean diameters of 51 and 60 mu, respectively, and estimated average volumes of 90 and 142 pL. On the basis of existing data on the correlation between size and lipolytic activity of fat cells, the smaller size of the adipocytes from HP-fed rats might account for the lower rate of basal lipolysis but not for the increased response to the hormones. The increased sensitivity of fat cells to the antilipolytic action of insulin may have been an important factor in the reduced lipomobilization during fasting in rats under the high-protein regimen.

Adaptation, Physiological↗