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Biomedical subjects

G Boden

Publications and source records attributed to G Boden.

At least 127 records · Page 7Linked to original sources
PubMed1983

Nature and quantity of fuels consumed in patients with alcoholic cirrhosis.

Although alcoholism is a leading cause of morbidity and mortality of middle-aged Americans, there are no data available pertaining to the consequences of Laennec's cirrhosis on total body energy requirements or mechanisms for maintaining fuel homeostasis in this patient population. Therefore, we simultaneously used the techniques of indirect calorimetry and tracer analyses of [14C]palmitate to measure the nature and quantity of fuels oxidized by patients with biopsy-proven alcoholic cirrhosis and compared the results with values obtained from health volunteers. Cirrhotic patients were studied after an overnight fast (10-12 h). Normal volunteers were studied after an overnight fast (12 h) or after a longer period of starvation (36-72 h). Total basal metabolic requirements were similar in overnight fasted cirrhotic patients (1.05 +/- 0.06 kcal/min per 1.73 m2), overnight fasted normal subjects (1.00 +/- 0.05 kcal/min per 1.73 m2), and 36-72-h fasted normal volunteers (1.10 +/- 0.06 kcal/min per 1.73 m2). Indirect calorimetry revealed that in cirrhotic patients the percentages of total calories derived from fat (69 +/- 3%), carbohydrate (13 +/- 2%), and protein (17 +/- 4%) were comparable to those found in 36-72-h fasted subjects, but were clearly different from those of overnight fasted normal individuals who derived 40 +/- 6, 39 +/- 4, and 21 +/- 2% from fat, carbohydrate, and protein, respectively. These data are strikingly similar to data obtained through tracer analyses of [14C]palmitate, which showed that in overnight fasted patients with alcoholic cirrhosis, 63 +/- 4% of their total CO2 production was derived from oxidation of 287 +/- 28 mumol free fatty acids (FFA)/min per 1.73 m2. In contrast, normal overnight fasted humans derived 34 +/- 6% of their total CO2 production from the oxidation of 147 +/- 25 mumol FFA/min per 1.73 m2. On the other hand, values obtained from the normal volunteers fasted 36-72 h were similar to the overnight fasted cirrhotic patients. These results show that after an overnight fast the caloric requirements of patients with alcoholic cirrhosis are normal, but the nature of fuels oxidized are similar to normal humans undergoing 2-3 d of total starvation. Thus, patients with alcoholic cirrhosis develop the catabolic state of starvation more rapidly than do normal humans. This disturbed but compensated pattern for maintaining fuel homeostasis may be partly responsible for the cachexia observed in some patients with alcoholic cirrhosis. This study also showed remarkably good agreement between the results obtained with indirect calorimetry and those obtained with 14C tracer analyses.

Adult↗
PubMed1983

Effect of spontaneous diabetes on hormone release in BB/Phi rats: comparison between the isolated perfused pancreas/stomach/duodenum/spleen and the isolated perfused pancreas.

We have studied the effects of spontaneous diabetes in BB/Phi rats on hormone release in response to amino acids (15 mM) and to amino acids (15 mM) plus glucose (10 mM) from isolated perfused pancreas/stomach/duodenum/spleen (PSDS) and from isolated perfused pancreas (P) preparations. In the PSDS preparation, diabetes reduced total integrated insulin output by 97% (from 1146 +/- 198 to 40 +/- 24 ng/65 min, P less than 0.001), and glucagon output by about 50% (from 51.6 +/- 13.1 to 24.0 +/- 3.7 ng/65 min, P less than 0.05), whereas somatostatin output did not change (105.5 +/- 48.1 to 110.1 +/- 36.9 ng/65 min). In the P preparation, integrated glucagon output fell by 91% (from 97.9 +/- 26.8 to 8.6 +/- 4.8 ng/65 min, P less than 0.01) whereas integrated somatostatin output more than doubled (from 28.1 +/- 7.5 to 69.6 +/- 14.2 ng/65 min, P less than 0.05). Intestinal glucagon and somatostatin contributions were estimated by comparing hormone release from the PSDS with that from the P preparations. We conclude that in our nondiabetic BB/Phi rats, the pancreas was the only source for the release of glucagon and that the intestinal tract secreted more somatostatin than the pancreas. In the diabetic BB/Phi rats, pancreatic glucagon and insulin release was virtually abolished while glucagon secretion from the intestinal tract increased and somatostatin secretion decreased.

Animals↗
PubMed1983

Counterregulatory hormone release and glucose recovery after hypoglycemia in non-insulin-dependent diabetic patients.

An increasing number of patients with non-insulin-dependent diabetes mellitus (NIDDM) is presently being treated with insulin, some aggressively with intensified treatment schedules. However, there is little information on the ability of these patients to recover from insulin-induced hypoglycemia. We have, therefore, determined glucose recovery and counterregulatory hormone secretion in response to insulin-induced hypoglycemia in 10 NIDDM patients without autonomic neuropathy and in 6 age- and weight-matched normal controls. Recovery of plasma glucose concentration and hypoglycemia-induced increments of plasma concentrations of glucagon, epinephrine, norepinephrine, and HGH were similar in the NIDDM patients and the age- and weight-matched nondiabetic controls. It appears likely, therefore, that these NIDDM patients, if treated aggressively with insulin, may be at lesser risk for severe and prolonged hypoglycemia than insulin-dependent diabetic patients, particularly those with autonomic neuropathy or those treated with beta-adrenergic antagonists.

Adult↗
PubMed1983

Carbohydrate oxidation and storage in obese non-insulin-dependent diabetic patients. Effects of improving glycemic control.

We have determined total body carbohydrate and lipid oxidation rates in response to a standard breakfast in nine obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and in seven age- and weight-matched controls. The patients with NIDDM were studied twice, once while in poor glycemic control (fasting blood glucose concentration 267 +/- 24 mg/dl, urinary glucose excretion 28.9 +/- 6.3 g/24 h) and again after modest glycemic improvement following 2 mo of fiber treatment (fasting blood glucose 227 +/- 19 mg/dl, urinary glucose excretion 10.7 +/- 1.9 g/24 h). Basal carbohydrate (CHO) oxidation rates were normal in patients with NIDDM before and after fiber treatment. However, in patients before fiber treatment the rise in CHO oxidation rates, the reciprocal fall in lipid oxidation rates, and the rise in serum insulin and C-peptide concentrations after the breakfast were all severely blunted. In addition, storage of ingested CHO was significantly reduced (from 55% to 32%, P less than 0.05). After fiber treatment, postbreakfast CHO oxidation rates had improved and were no longer significantly lower than control values. In contrast, CHO storage remained suppressed. We conclude that (1) basal CHO oxidation remained normal but that postbreakfast CHO oxidation was impaired in our obese patients with NIDDM. This impairment, however, appeared to be a relatively late event, occurring only during severely uncontrolled NIDDM. (2) Inability to dispose of CHO by storage appeared to be an earlier defect with a greater impact on glucose tolerance than the impairment of CHO oxidation.

Adult↗
PubMed1983

Assessment of norepinephrine secretion and production.

A noninvasive method is described for assessing the disposition of NE produced by peripheral sympathetic neurons. Total NE production is estimated from integrated NE metabolite excretion. The rate at which NE enters the bloodstream (apparent NE secretion) is estimated by isotope dilution analysis. The rate at which NE is metabolized locally is calculated by subtracting apparent NE secretion from NE production. In 10 normal volunteers, basal NE production by the peripheral sympathetic nervous system was 11.1 +/- 1.0 nmol/m2/min. Apparent NE secretion, by contrast, was only 2.4 +/- 0.18 nmol/m2/min. Our data thus demonstrate that in normal individuals under basal conditions, at least 78% of the NE produced by the sympathetic nervous system undergoes local metabolism and that no more than 22% of NE diffuses into the circulation.

Adult↗
PubMed1982

Adrenergic control of somatostatin release.

The effects of adrenergic stimulation and suppression on somatostatin (SS), insulin, and glucagon release were studied in intact dogs. Isoproterenol, a beta-adrenergic agonist, significantly increased portal venous and arterial levels of SS and arterial levels of insulin and glucagon. Propranolol, a beta-adrenergic antagonist, significantly decreased portal venous SS and suppressed the isoproterenol-stimulated increases in the levels of SS, insulin, and glucagon. alpha-Adrenergic stimulation (propranolol plus epinephrine) decreased portal venous SS and arterial insulin. Phentolamine, and alpha-adrenergic antagonist, increased portal venous and arterial SS and arterial glucagon. These data suggest that in intact dogs, stimulation of beta-adrenergic receptors enhances the release of SS, insulin, and glucagon, while stimulation of alpha-adrenergic receptors inhibits the release of SS and insulin without having a definitive effect on glucagon.

Animals↗
PubMed1982

Acetone metabolism during diabetic ketoacidosis.

The presence and the importance of acetone and its metabolism in diabetic ketoacidosis has largely been ignored. Therefore, we studied acetone metabolism in nine diabetic patients in moderate to severe ketoacidosis. The concentration of acetone in plasma, urine, and breath, and the rates of acetone production and elimination in breath and urine were determined and the rates of vivo metabolism were calculated. Plasma acetone concentrations (1.55-8.91 mM) were directly related and were generally greater than acetoacetate concentrations (1.16-6.08 mM). The rates of acetone production ranged from 68 to 581 mumol/min/1.73 m2, indicating the heterogeneous nature of the patients studied. The average acetone production rate was 265 mumol/min/1.73 m2 and accounted for about 52% of the estimated acetoacetate production rate. Urinary excretion of acetone remained constant and accounted for about 7% of the acetone production rate in all patients. There was a positive linear relationship between the percentage of the acetone production rate accounted for by excretion in breath and the plasma acetone concentration. At low plasma acetone concentrations, approximately 20%, and at high plasma acetone concentrations, approximately 80% of the production rate was accounted for by breath acetone. In contrast, there was a negative linear relationship between the percentage of acetone production rate undergoing in vivo metabolism and plasma acetone concentration. At low plasma acetone concentrations, approximately 75%, and at high concentrations, approximately 20% of acetone production rate was accounted for by in vivo metabolism. Radioactivity from 2-[14C]-acetone was variably present in plasma acetone, glucose, lipids and proteins. No radioactivity was found in plasma acetoacetate, beta-hydroxy butyrate or free fatty acids or other anionic compounds. Exchange rates of acetone into other metabolites could not be estimated because of non-steady-state precursor product relationships in these patients.

Acetone↗
PubMed1982

Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy.

The cause of susceptibbility of certain diabetic patients to severe hypoglycemia is not known. Because the awareness of hypoglycemia is heightened by catecholamine-mediated physiologic responses, deficient catecholamine secretion may cause frequent and severe hypoglycemia. Plasma epinephrine and norepinephrine were measured after insulin-induced hypoglycemia in 18 diabetic patients, nine with autonomic neuropathy, and in nine normal volunteers. Our results show that two thirds of patients with diabetic autonomic neuropathy have moderate to severe deficits in epinephrine secretion and that these patients have diminished or delayed subjective responses to low blood sugar and are at risk for developing severe hypoglycemia and its neurologic consequences.

Autonomic Nervous System Diseases↗
PubMed1981

Identification, characterization, and distribution of secretin immunoreactivity in rat and pig brain.

Secretin immunoreactivity was detected in the central nervous system of the rat and pig with a highly specific radioimmunoassay. The secretin immunoreactivity in the rat and pig brain and duodenum extracts was fractionated by using a reverse-phase high-pressure liquid chromatographic system. The immunoreactive secretin from pig brain and duodenum coeluted precisely with synthetic porcine secretin. However, immunoreactive secretin extracted from rat brain and duodenum eluted slightly before porcine secretin. These data suggest a slight difference in the structure of rat and pig secretin. The detection of secretin in the brain lays the groundwork for studies to determine the role of the peptide in central nervous system function.

Animals↗
PubMed1981

Effects of starvation and obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system.

We have studied the effects of starvation and of obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system in fed and 3- and 5-day fasted Holtzman rats and in obese (fa/fa) and lean (Fa/?) Zucker rats. Fasting for 3 days significantly decreased basal (-71%) and amino acid-stimulated (-62%) somatostatin output. After 5 days of starvation, there was a significant increase over the 3-day level in somatostatin output stimulated by amino acid plus glucose (+540%) and by amino acids plus tolbutamide (+238%). Three and five days of starvation severely depressed insulin output while having no statistically significant effects on glucagon secretion. Somatostatin output from obese Zucker rats was significantly greater than that from lean controls in response to amino acids (41.2 +/- 13.2 vs. 16.3 +/- 10.3 ng/25 min, P less than 0.05). Insulin output was greatly increased from obese compared to lean Zucker rats, whereas there were no statistically significant differences in glucagon output. These data show that fasting decreases and obesity increases both somatostatin and insulin release. They suggest that altered stimulation by nutrients was primarily responsible for changes in somatostatin and insulin release observed in starving and obese rats.

Amino Acids↗
PubMed1981

Hepatic, gut, and renal substrate flux rates in patients with hepatic cirrhosis.

The roles of liver, kidney, and gut in maintaining fuel homeostasis were studied in 28 patients with severe hepatic cirrhosis, 25 of whom had alcohol-induced cirrhosis. Hepatic, portal, and renal blood flow rates were measured and combined with substrate concentration differences across liver, gut, and kidney to calculate the net flux of free fatty acids, ketone bodies, triglycerides, and glucose with selected glucose precursors, including glycerol, lactate, pyruvate, and amino acids. Data from the catheterization studies were related to hepatic histology, glycogen content, and activities of gluconeogenic enzymes and compared with data obtained from control patients. The effects of food deprivation on net flux of fuels across the liver, gut, and kidney were assessed after overnight and after 3d of fasting. Activities of gluconeogenic enzymes were normal, but hepatic glycogen content was diminished in cirrhotic livers, probably as a consequence of extensive hepatic fibrosis. Extrahepatic splanchnic tissues (gut) had only a small influence on total splanchnic flux rates of carbohydrates, lipids and, amino acids. In cirrhotic patients, there was no mean renal glucose contribution to the bloodstream after an overnight or after a 3-d fast. After an overnight fast hepatic glucose production in patients with cirrhosis was diminished as a result of low-rate glycogenolysis. Hepatic gluconeogenesis and ketogenesis were increased. This pattern of hepatic metabolism mimics that seen in "normal" patients after more advanced stages of starvation. After 3 d of starvation, patients with hepatic cirrhosis have hepatic gluconeogenic and ketogenic profiles comparable to those of normal patients undergoing starvation of similar duration. Nevertheless, the total number of caloric equivalents derived from ketone bodies plus glucose corrected for recycled lactate and pyruvate added to the bloodstream by the cirrhotic livers that could be terminally oxidized by peripheral tissues was less than the contributions made by the normal livers, both after and overnight and after a 3-d fast.

Adult↗
PubMed1980

Splanchnic somatostatin: a hormonal regulator of nutrient homeostasis.

Free (approximately 1600 daltons) somatostatin-like immunoreactivity was identified in arterial plasma of dogs that had received a test meal. Neutralization of circulating somatostatin while the dogs were consuming a fatty meal increased the plasma concentrations of triglycerides, gastrin, pancreatic polypeptide, and insulin after the meal. It is concluded that, in the dog, somatostatin is a true hormone that regulates the movement of nutrients from the gut to the internal environment.

Animals↗
PubMed1980

Substrate, hormone, and temperature responses in males and females to a common breakfast.

To evaluate the response to a mixed meal we studied oral temperature, metabolite, and hormonal responses to a common American breakfast containing 11 kcal/kg body weight (carbohydrate 43%, fat 42%, and protein 15%) in 12 normal volunteers (6 males and 6 females). There was a significant rise in oral temperature during the postcibal period. This change in oral temperature did not depend upon food consumption in males but was meal-dependent in females. Food ingestion caused increases in the peripheral circulating concentrations of glucose, lactate, pyruvate, and amino acids and reciprocal decreases in the concentrations of free fatty acids, glycerol, and urea nitrogen. Acetoacetate and beta-hydroxybutyrate decreased during the postcibal period but the changes were not statistically significant. Although peripheral venous serum insulin and plasma glucagon concentrations were indistinguishable between the sexes, males had higher concentrations of plasma triglycerides, plasma amino acids, and serum urea nitrogen. Peripheral venous plasma somatostatin and secretin remained unchanged, but pancreatic polypeptide hormone showed a large biphasic response to the meal. After breakfast the blood glucose concentration tended to be greater in males than in females and this difference was significant at 60 and 120 min postcibal. Furthermore, every female had a 120 min postcibal glucose concentration that was lower than her basal fasting glucose concentration. This suggests that postcibal glucose concentrations should be related to gender in making the diagnosis of carbohydrate intolerance or reactive hypoglycemia.

Adult↗
PubMed1980

Glucagon deficiency and hyperaminoacidemia after total pancreatectomy.

The first goal of this study was to investigate whether totally pancreatectomized patients are glucagon deficient and if so, to what degree. Immunoreactive glucagon (IRG) concentrations in peripheral plasma of nine pancreatectomized patients were not significantly different from those of 10 normal controls as measured by two antisera (30-K and RCS-5) both detecting the COOH-terminal portion of the molecule and one (RCS-5) postulated to be specific for pancreatic glucagon. Plasma from six of nine pancreatectomized patients were fractionated over Sephadex G-50 and IRG was measured with both antisera in the column eluates. Using 30-K, 80.8 +/- 9% of the IRG eluted within the void volume. This material was rechromatographed on Sephadex G-200 and found to have an apparent mol wt of approximately 200,000. Only 18.3 +/- 9% eluted in the IRG3500 region. IRG3500 was significantly reduced in pancreatectomized patients as compared to normal controls (49 +/- 9 vs. 18 +/- 9 pg/ml, P less than 0.05). Using RCS-5, all IRG (corresponding to 20 +/- 6 pg/ml of plasma) eluted in the IRG3500 region. The second goal of this study was to investigate the effects of chronic glucagon deficiency on plasma amino acids. In the nine pancreatectomized patients studied, postabsorptive plasma concentrations of serine, alanine, arginine, glycine, threonine, citrulline, alpha-aminobutyrate, and tryosine were significantly elevated compared to values obtained from 20 normal controls. Physiological glucagon increments produced in two pancreatectomized patients by infusion of glucagon (6.25 and 8.0 microgram/h, respectively) resulted in normalization of the hyperaminoacidemia within 22 h. We conclude (a) that pancreatectomized patients are partially glucagon deficient because of diminished basal as well as diminished stimulated glucagon secretion; (b) that fasting concentrations of certain glucogenic amino acids are elevated in pancreatectomized patients probably as result of reduce; hepatic gluconeogenesis; and (c) that the RCS-5 antiserum is not "pancreatic glucagon" specific.

Adult↗
PubMed1980

Human pancreatic polypeptide in chronic renal failure and cirrhosis of the liver: role of kidneys and liver in pancreatic polypeptide metabolism.

Basal plasma concentrations of human pancreatic polypeptide (PP) were measured in 14 patients with chronic renal failure (CRF), 13 patients with cirrhosis of the liver, and age-matched controls. PP was significantly higher in patients with CRF than in controls (817 +/- 183 vs. 157 +/- 118 pg/ml; P < 0.005). The degree of PP elevation in patients with CRF correlated well with the degree of their renal insufficiency (r = 0.85; P < 0.001). Fractionation of plasma over Sephadex G-50 columns revealed comparable elution patterns in patients with CRF and in normal controls. Hemodialysis had no effect on the PP concentration. We also determined arterial venous PP concentration differences and plasma blood flow across the kidneys and liver in 13 patients with cirrhosis and arteriovenous differences across of the liver in 13 controls with normal hepatic and renal functions. The mean PP concentration was significantly higher in arterial plasma than in renal venous plasma (143 +/- 24 vs. 123 +/- 23 pg/ml; P < 0.025). Renal fractional extraction was 17.2 +/- 6.6%, and renal clearance of PP was 151 +/- 47 ml/min. No significant extraction of PP occurred across the liver. It is concluded that the kidneys, but not the liver, are important sites for the metabolism of PP and that elevated PP concentrations in patients with CRF may contribute to their uremic syndrome.

Adult↗