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Biomedical subjects

G Boden

Publications and source records attributed to G Boden.

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

Treatment of autonomic neuropathy with a somatostatin analogue SMS-201-995.

Eight patients with postprandial hypotension and orthostatic hypotension were treated with the somatostatin analogue SMS-201-995. Low doses of this drug (0.2-0.4 microgram/kg) raised the blood pressure after breakfast in all six patients with postprandial hypotension. 60 min after breakfast the mean sitting blood pressure was 35 +/- 10 (SEM) mm Hg higher after administration of SMS-201-995 0.4 microgram/kg than after placebo (p less than 0.001). Larger doses (up to 1.6 micrograms/kg) raised upright blood pressure during the postprandial period in five of seven patients. Before therapy three patients were unable to stand after eating; after an injection of SMS-201-995 0.8 microgram/kg at the beginning of breakfast they were able to walk for 35-100 min. The duration of therapeutic effect of each injection was 3-6 h. Treatment was followed by abdominal cramps and nausea in two patients with gastroparesis diabeticorum. SMS-201-995 holds promise as a treatment for postprandial hypotension and orthostatic hypotension.

Adult↗
PubMed1986

A reappraisal of caloric requirements in healthy women.

The caloric expenditure of 44 healthy, lean and obese women, 8 of whom were trained athletes, was measured by indirect calorimetry. Body composition was determined. Ages ranged from 18-65 yr and body weights from 43-143 kg. Stepwise, multiple-regression analysis was used to determine whether one or several variables best predicted the resting metabolic rate (RMR) of the women. The RMR and the thermic effect of food (TEF) were measured before and after the women consumed a mixed breakfast meal. The results showed that the currently available tables and regression equations overestimate the RMR of healthy women by 7-14%. Body weight was highly related to the RMR, and stepwise inclusions of various variables did not improve predictions of RMR. The slopes of the regression lines for nonathletes and athletes were significantly different. Regression equations for predicting RMR of women were developed: Nonathletes RMR = 795 + 7.18 kg WT; Athletes RMR = 50.4 + 21.1 kg WT. The range of RMR per kilogram body weight was wide for nonathletic, but narrow for athletic women. The metabolism of some lean and obese, nonathletic women was highly efficient, predisposing these women for developing and maintaining body fat. The TEFs were indistinguishable between nonathletic and athletic women, and formed a continuum from the lightest to the heaviest woman.

Adolescent↗
PubMed1986

Effects of anti-insulin receptor antibodies (AIRA) on downregulation and turnover of insulin receptors on cultured hepatocytes.

We have studied the effects of two polyclonal anti-insulin receptor antibodies (AIRA) on insulin receptor downregulation and turnover in rat hepatocytes in primary culture. Downregulation was determined by measurement of insulin binding after acid washing of cells to remove AIRA. Insulin receptor turnover was estimated by measurement of insulin binding after inhibition of synthesis of functional receptors with tunicamycin (0.5 micrograms/ml). Exposure of hepatocytes to AIRA (both sera were of comparable effectiveness) resulted in progressive, time- and dose-dependent losses of insulin binding (maximal loss was about 55% after 24 h of incubation with AIRA diluted 1:25). Cycloheximide (100 microM) prevented AIRA-mediated downregulation. The t1/2 of disappearance of cell surface insulin binding capacity determined with tunicamycin was 8.0 h. Addition of insulin (1000 ng/ml) or AIRA to tunicamycin reduced the t1/2 to 2.6 h (insulin), 2.2 h (patient B10), and 2.0 h (patient 1). These data suggest that AIRA downregulated insulin receptors on cultured hepatocytes by accelerating their rate of disappearance, inhibition of protein synthesis prevented AIRA-mediated downregulation, and downregulation by AIRA of insulin binding may be partially responsible for the desensitization of target cells to some of the insulin-like actions of these autoantibodies.

Animals↗
PubMed1986

Insulin and a sulfonylurea agent in non-insulin-dependent diabetes mellitus.

Using a double-blind crossover design, we studied the effect of tolazamide, an orally administered sulfonylurea, in 11 patients with non-insulin-dependent diabetes mellitus, poorly controlled on 40 units/day or more of insulin; all had previously failed to respond adequately to oral hypoglycemic agents and diet. In addition, six nondiabetic sex-, age-, and weight-matched controls were studied. Tolazamide significantly lowered fasting plasma glucose level from 272 +/- 21 to 222 +/- 31 mg/dL, increased fasting C peptide concentration from 0.09 +/- 0.03 to 0.28 +/- 0.10 pmole/mL (controls, 0.23 +/- 0.2 pmole/mL), and increased integrated C peptide concentration during a test meal (area under the curve) from 42 +/- 18 to 95 +/- 22 pmole/mL X min (controls, 94 +/- 8 pmole/mL X min). These data show that addition of tolazamide markedly increased fasting and meal-stimulated insulin secretion and modestly lowered fasting plasma glucose concentrations. We conclude that some patients who cannot achieve satisfactory control with oral hypoglycemic agents and diet may benefit from combined therapy with oral sulfonylurea agents plus insulin.

Administration, Oral↗
PubMed1985

Treatment strategies for patients with non-insulin-dependent diabetes mellitus.

Strategies for the treatment of patients with non-insulin-dependent diabetes mellitus are discussed. In order to achieve treatment goals, diet and exercise remain important components of an overall treatment program that may include sulfonylurea drugs, especially in cases where patients are of normal weight or only slightly obese, have had the disease less than five years, and are taking little or no insulin. Failure to control blood sugar levels with sulfonylurea drugs may lead to combining this therapy with insulin or administering insulin alone, regardless of patients' weights.

Arginine↗
PubMed1985

Mebendazole and insulin secretion from isolated rat islets.

In a preliminary communication we reported that mebendazole, a vermicide, decreased plasma glucose and free fatty acid concentrations and increased plasma C peptide concentrations in both type II diabetic patients. Therefore, we suggested that mebendazole was an insulin secretagogue. However, these were uncontrolled studies, and improved metabolic control in these patients due to spontaneous remission rather than drug-induced insulin secretion was a possibility. To investigate the direct effect of mebendazole on insulin secretion we used intact islets isolated from normal rat pancreata. Mebendazole in concentrations as low as 10 to 20 mumol/L caused a twofold to threefold increase in acute-phase insulin release from isolated perifused rat islets. This heightened insulin release occurred in the presence of glucose-stimulated insulin secretion.

Animals↗
PubMed1985

Hepatic and renal metabolism before and after portasystemic shunts in patients with cirrhosis.

Hepatic cirrhosis with portal hypertension and gastroesophageal hemorrhage is a disease complex that continues to be treated by surgical portasystemic shunts. Whether or not a reduction or diversion of portal blood flow to the liver adversely affects the ability of the liver to maintain fuel homeostasis via gluconeogenesis, glycogenolysis, and ketogenesis is unknown. 11 patients with biopsy-proven severe hepatic cirrhosis were studied before and after distal splenorenal or mesocaval shunts. Hepatic, portal, and renal blood flow rates and glucose, lactate, pyruvate, glycerol, amino acids, ketone bodies, free fatty acids, and triglyceride arteriovenous concentration differences were determined to calculate net precursor-product exchange rates across the liver, gut, and kidney. The study showed that hepatic contribution of glucose and ketone bodies and the caloric equivalents of these fuels delivered to the blood was not adversely affected by either a distal splenorenal or mesocaval shunt. In addition to these general observations, isolated findings emerged. Mesocaval shunts reversed portal venous blood and functionally converted this venous avenue into hepatic venous blood. The ability of the kidney to make a substantial net contribution of ketone bodies to the blood was also observed.

Adult↗
PubMed1985

Effects of antiinsulin receptor antibodies on amino acid uptake by cultured rat hepatocytes.

The effects of two antiinsulin receptor antisera (AIRA) on alpha-amino-2-[14C]isobutyric acid [( 14C]AIB) uptake by and [125I]insulin binding to cultured rat hepatocytes were examined. Diluted 1:100, both antisera inhibited insulin binding by 75-80%, mainly by decreasing available high affinity insulin-binding sites. Diluted 1:500, they decreased insulin binding and high affinity binding sites by 35-40%. Neither antiserum had an effect on basal [14C]AIB uptake, but decreased insulin-stimulated AIB uptake by 83% (dilution, 1:100; 24-h incubation) and 25% (dilution, 1:500; 24-h incubation), respectively. Insulin stimulation of AIB uptake correlated positively (r = 0.96; P less than 0.01) with insulin binding to high affinity receptors on hepatocytes incubated with normal serum or AIRA. We conclude that: 1) insulin stimulation of amino acid uptake by hepatocytes was mediated through insulin receptors, especially high affinity binding sites, and was inhibited by AIRA in parallel with receptor blockade; and 2) AIRA had no insulin-like effect on basal amino acid uptake by hepatocytes.

Amino Acids↗
PubMed1985

Effects of anti-insulin receptor antibodies on in vivo insulin metabolism.

The effects of anti-insulin receptor antibodies (AIRA) on receptor binding and insulin metabolism were studied in two patients with the type B, severe insulin resistance syndrome. Insulin binding was determined using rat hepatocytes in primary culture and the patient's own red blood cells. Plasma and urinary insulin concentrations and metabolic clearance rates (MCR) were determined in the two patients and in four normal controls in response to infusions of insulin for 60-120 min at rates ranging from 1 to 925 mU/kg/min. In patient 1, basal insulin concentration was 1400 microU/ml. After infusion of 1, 10, and 925 mU/kg/min of insulin it rose to 3800, 5500, and 225,000 microU/ml, respectively. Respective MCRs were 19, 110, and 186 ml/min. In patient 2, basal insulin concentration was 440 microU/ml. After infusion of 1, 10, and 100 mU/kg/min of insulin it rose to 720, 2500, and 18,800 microU/ml, respectively. Respective MCRs were 193, 262, and 294 ml/min. In controls, basal insulin concentration was 4 +/- 0.3 microU/ml. After infusion of 1 and 10 mU/kg/min of insulin, it rose to 82 +/- 17 and 1288 +/- 50 microU/ml. Respective MCRs were 950 and 630 ml/min. These data showed that, in patients with AIRA: (1) insulin metabolism took place at the same rate but at higher insulin concentrations than in normal controls, and (2) MCR increased with rising insulin concentration but remained subnormal even at the highest insulin concentrations. In contrast, MCR in normal controls decreased with increasing insulin concentrations. The data suggest that prevention of insulin binding prevents insulin metabolism at physiologic insulin concentrations and that supraphysiologically elevated insulin concentrations are needed to activate nonreceptor mechanisms.

Adult↗
PubMed1985

Carbohydrate (CHO) oxidation in patients with type B insulin resistance.

Total body carbohydrate (CHO) and fat oxidation rates, plasma glucose, free fatty acid, and insulin concentrations were determined in two patients with the type B syndrome of severe insulin resistance and in normal controls in response to insulin infusions (1-100 mU/kg/min) and to a test meal. In addition, insulin was infused at higher rates (10-1000 mU/kg/min) in one of the two patients while plasma glucose concentrations were clamped first at 195 and later at 244 mg/dl. During the postabsorptive state, resting metabolic rates (RMR) were 914 and 979 cal/min/1.73 m2 in the two patients (controls: 1018 +/- 85 cal/min/1.73 m2). Patients met 85% and 83% of their caloric requirements by oxidizing fat (controls: 63 +/- 7%). Protein oxidation accounted for 15% and 13% (controls: 14 +/- 3%) of energy requirements and CHO oxidation for 0% and 0%, respectively, in both patients (controls: 23 +/- 5%). Infusion of insulin at a rate of 10 mU/kg/min raised plasma insulin concentrations from 1400 and 440 microU/ml to 6000 and 2500 microU/ml, respectively, in patients 1 and 2 (controls: from 4 +/- 0.3 to 1288 +/- 50 microU/ml), but had no effects on rates of CHO, fat, or protein oxidation in either patient. By comparison, the rate of CHO oxidation in controls rose about sixfold from 40 +/- 8 to 234 +/- 12 mg/min/1.73 m2. Infusion of 1000 mU/kg/min in combination with an increase in plasma glucose from 195 +/- 1.1 to 244 +/- 1.9 mg/dl in patient 1, however, raised CHO oxidation from 0 to 36 mg/min/1.73 m2 and lowered fat oxidation from 105 to 69 mg/min/1.73 m2.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthosis Nigricans↗
PubMed1984

Improvement of metabolic control in diabetic patients during mebendazole administration: preliminary studies.

After the observation of decreasing insulin resistance in a diabetic patient during treatment with mebendazole for nematosis, we investigated the effect of mebendazole on metabolic control in six Type 1 (insulin-dependent) and six Type 2 (non-insulin-dependent) diabetic patients, eight of whom were chronically resistant to conventional treatment. Before and after mebendazole treatment for 1 month, plasma glucose and serum C-peptide concentrations were determined both fasting and 4 h after a mixed breakfast. Improvements in fasting blood glucose concentrations occurred in Type 1 (12.83 +/- 1.11 versus 6.56 +/- 0.56 mmol/l; p less than 0.05) and Type 2 (10.22 +/- 0.56 versus 7.56 +/- 0.67 mmol/l; p less than 0.05) diabetic patients and were associated with increases in post-cibal C-peptide responses in Type 1 and Type 2 diabetic patients. Following discontinuation of mebendazole, metabolic control deteriorated in five out of the six Type 1 diabetic patients and in all the Type 2 diabetic patients. We conclude that mebendazole increases insulin secretion, and decreases plasma glucose concentration in Type 1 and Type 2 diabetic patients. However, these beneficial effects may be transient.

Adult↗
PubMed1984

Effects of glucagon on plasma amino acids.

The effects of glucagon deficiency and excess on plasma concentrations of 21 amino acids were studied in six normal human subjects for 8 h. During glucagon deficiency, produced by intravenous infusion of somatostatin (0.5 mg/h) and insulin (5 mU/kg per h), amino acid concentration (sum of 21 amino acids) rose from 2,607 +/- 76 to 2,922 +/- 133 microM after 4 h (P less than 0.025). The largest increases occurred in lysine (+26%), glycine (+24%), alanine (+23%), and arginine (+23%) concentrations. During glucagon excess produced by intravenous infusion of somatostatin (0.5 mg/h), insulin (5 mU/kg per h), and glucagon (60 ng/kg per h), amino acid concentration decreased from 2,774 +/- 166 to 2,388 +/- 102 microM at 8 h (P less than 0.01). The largest decreases occurred in citrulline (-37%), proline (-32%), ornithine (-30%), tyrosine (-23%), glycine (-20%), threonine (-21%), and alanine (18%) concentrations. Urinary urea nitrogen and total nitrogen excretions were lower during glucagon deficiency than during glucagon excess (3.1 +/- 0.2 vs. 6.3 +/- 2.3 g/8 h, P less than 0.05 and 4.8 +/- 1.0 vs 7.0 +/- 2.6 g/8 h, respectively, P less than 0.05). Biostator-controlled euglycemic glucagon deficiency was produced in four normal subjects for 4 h to eliminate possible effects of changes in glucose concentration on amino acids. Amino acid concentration (sum of 18 amino acids) increases occurred in arginine (+42%), alanine (+28%), glutamine (+25%), and glycine (+16%) concentrations. The data show that small changes (-66 pg/ml and +50 pg/ml) in basal glucagon concentrations cause plasma amino acid concentrations to change in opposite directions. The finding that urinary excretion of nitrogen and urea nitrogen was greater during glucagon excess than during glucagon deficiency suggested alterations in the rate of gluconeogenesis from amino acids as one mechanism by which glucagon controls blood amino acid levels.

Adult↗
PubMed1984

In vivo and in vitro effects of antiinsulin receptor antibodies.

We studied a patient with Acanthosis nigricans and the type B syndrome of severe insulin resistance. The patient's rates of basal glucose disappearance and appearance were both normal (2.2 and 1.7 mg/kg . min, respectively). FFA, betahydroxybutyrate, and acetoacetate concentrations were stable at 0.8, 1.0, and 0.3 mM, respectively, during a 2-h saline infusion after an overnight fast, indicating continued presence of insulin-like activity (ILA) in her serum. Infusion of insulin at rates of 2.7 and 27 U/h, raising peripheral insulin concentrations from 1400 to 4000 and 6000 microU/ml, respectively, had no effect on glucose disappearance and appearance or plasma concentrations of beta-hydroxybutyrate, acetoacetate, and FFA, suggesting that the observed ILA was not caused by the patient's plasma insulin. To determine the source of the ILA we used the patient's serum containing antiinsulin receptor antibodies (AIRA) to study its acute (2 h) and chronic (24 h) effects on insulin binding and glycogen synthesis in rat hepatocytes in primary culture. Preincubation of hepatocytes with AIRA serum (diluted 1:100) inhibited insulin binding by 84% and 88% after 2 and 24 h, respectively. It increased U-[14C]glucose incorporation into glycogen by 40% and 52% after 2 and 24 h, respectively. These effects were not caused by insulin present in the patient's serum. We conclude that AIRA serum, in addition to causing severe insulin resistance through inhibition of insulin binding, also exerted strong and long lasting insulin-like effects. These findings are compatible with the patient's clinical features of absence of ketoacidosis despite severe insulin resistance, decrease in glucose concentrations during fasting, and postprandial hyperglycemia.

Adult↗
PubMed1984

Glucose metabolism in cachectic patients with colorectal cancer.

We have studied a defined group of 12 weight-losing patients with metastatic colorectal cancer to evaluate the occurrence of and possible relationship between those determinants of carbohydrate metabolism which have been reported to occur commonly in cancer cachexia. The rates of endogenous glucose production and recycling via lactate (Cori cycle) were measured following an infusion of 50 to 100 microCi of [1-14C]glucose. Compared to an age-related group of control subjects without cancer, significantly elevated rates of glucose production [136.4 +/- 9.0 (S.E.) versus 101.0 +/- 4.6 mg/kg/hr; p less than 0.01] and recycling (43.0 +/- 7.2 versus 15.4 mg/kg/hr; p less than 0.01) were observed. Values for glucose production and recycling ranged from normal to markedly elevated. Glucose tolerance was then determined following a p.o. glucose load of 40 g/sq m in 10 of the 12 patients. Compared to control subjects, all showed a significantly delayed clearance of glucose (p less than 0.01) and a blunted insulin-secretory responsiveness (p less than 0.025). Increased glucose production and recycling was only observed in the presence of carbohydrate intolerance, but the latter occurred in a manner which seemed independent of the rate of glucose turnover. In order to obtain an estimate of hepatic glycogen reserves, glucagon, 15 ng/kg/min, was infused over 40 min in seven subjects. A significantly blunted glycemic response was observed in the cancer patients compared to controls (delta 25.0 +/- 6.9 versus 57.8 +/- 8.5 mg/dl; p less than 0.025). Neither the rate of glucose production nor the glycemic response to glucagon appeared to correlate with the immediate antecedent caloric intake. An apparent relationship was observed, however, between increased glucose production and recycling and a lack of response to infused glucagon, probably reflecting decreased glycogen stores in the face of an increased glucose requirement by the patient. We have shown that diverse abnormalities of carbohydrate metabolism commonly occur in cancer cachexia and that significant metabolic heterogeneity may be expected, despite a uniform diagnosis. These results should prove useful in the interpretation and development of clinical studies on cancer cachexia.

Adenocarcinoma↗
PubMed1983

Long-term effects of dietary fiber on glucose tolerance and gastric emptying in noninsulin-dependent diabetic patients.

Effects of long-term (2 months) supplementation of diet with 20 g of guar gum and 10 g of wheat bran on metabolic control was studied in 12 obese, poorly controlled noninsulin-dependent diabetic patients. Addition of fiber reduced urinary excretion of glucose from 30.5 +/- 6 to 8.3 +/- 2 g/24 h, (p less than 0.025), fasting plasma glucose concentration from 301 +/- 24 to 184 +/- 15 mg/dl (p less than 0.025), and plasma cholesterol concentration from 277 +/- 24 to 193 +/- 9 mg/dl (p less than 0.025). No significant changes were observed in the patients weight and serum concentrations of triglycerides, high-density lipoproteins, free fatty acids, and insulin. Addition of fiber also delayed gastric emptying of liquids and solids. This effect became statistically significant 60 and 90 min after intake of a test meal for liquids and solids, respectively. We conclude that addition of guar and bran to the diet resulted in long-term improvement of metabolic control in these patients and that delayed gastric emptying may be one of the mechanisms responsible for this beneficial effect.

Adolescent↗