Biomedical subjects

W M Bennet

Publications and source records attributed to W M Bennet.

At least 19 recordsLinked to original sources

PubMed2002

Clinical experience of amiodarone-induced thyrotoxicosis over a 3-year period: role of colour-flow Doppler sonography.

OBJECTIVE: Current thinking is that amiodarone-induced thyrotoxicosis (AIT) might be either iodine-induced thyrotoxicosis in latent hyperthyroidism (Type 1) or destructive thyroiditis (Type 2), and also that colour-flow Doppler sonography (CFDS) of the thyroid and serum interleukin 6 (IL-6) are tools that can classify AIT and direct treatment. To assess the validity of this thinking, our objective was to determine whether CFDS and IL-6 identified AIT subgroups with distinct features. DESIGN: Retrospective case-note audit of all patients presenting with AIT to the Endocrine Department of a UK teaching hospital over a 3-year period. To assess proportions of Type 1 vs. Type 2 AIT and to compare and contrast their clinical features. PATIENTS: 37 patients were identified with AIT (mean age 65, range 20-86 years). In 30 patients in whom AIT persisted, 25 underwent CFDS. RESULTS: In 25 patients who underwent CFDS, 10 (40%) were classified as Type 1, 10 (40%) as Type 2 and 5 (20%) as indeterminate type. In the patients classified by CFDS in whom AIT persisted, 40% of Type 1 patients were male vs. 90% of Type 2 patients. Also, free T4 tended to be lower in patients presenting with Type 1 AIT (52.1 +/- 7.5 pmol/l) compared to Type 2 (74.8 +/- 8.1 pmol/l, P = 0.08), free T3 was lower (8.8 +/- 0.9 vs. 15.6 +/- 3.0 pmol/l, P = 0.03) and the cumulative amiodarone dose was lower (66 +/- 20 vs. 186 +/- 28 g, P = 0.002). We used less prednisolone to achieve euthyroidism in patients with Type 1 AIT whereas carbimazole doses were not different and the time to euthyroidism was the same in both groups (81 +/- 21 vs. 88 +/- 13 days). IL-6 was raised in two patients with Type 1 and in one patient with Type 2 AIT. CONCLUSIONS: CFDS could characterize two distinct subtypes in patients with AIT. Conversely, IL-6 seemed to be an unhelpful test in this context.

Adult↗

PubMed1997

Possible evidence for endogenous production of a novel galanin-like peptide.

Galanin mRNA and peptide are not detectable in normal islets. We studied the effect of galanin antagonists on insulin secretion in the rat beta cell line, RIN5AH, and in perifused rat islets. In RIN cell membranes galanin and its antagonists showed high affinity for 125I-galanin binding sites [Kd: (galanin) 0.03+/-0.01; Ki for galanin antagonists: (C7) 0.12+/- 0.02, (M35) 0.21+/-0.04, and (M40) 0.22+/-0.03 nM, mean+/- SEM, n = 4]. Galanin (1 microM) inhibited glucose-induced insulin release in islets (control 21.2+/-1.5 vs. galanin 4.5+/-0.2 fmol/islet per min, P < 0.001, n = 6) and RIN5AH cells (control 0.26+/-0.01 vs. galanin 0.15+/-0.02 pmol/10(6) cells per h, P < 0.001, n = 9). In RIN5AH cells, all antagonists blocked the inhibitory effects of galanin and stimulated insulin release in the absence of galanin. C7 and M40 (1 microM) alone significantly stimulated glucose-induced insulin secretion. Purified porcine galanin antibody (GAb) enhanced glucose-induced insulin release from islets (control 100+/- 16.3% vs. GAb 806.1+/-10.4%, P < 0.001, n = 6), and RIN5AH cells (control 100+/-9.6% vs. GAb 149+/-6.8%, P < 0. 01, n = 6). Western blotting of dexamethasone-treated islet extracts using GAb showed a specific band of similar molecular weight to porcine galanin not detected using a rat specific galanin antibody. One possible explanation for these results is the presence of an endogenous galanin-like peptide.

Amino Acid Sequence↗

PubMed1996

Presence of neuropeptide Y and its messenger ribonucleic acid in human islets: evidence for a possible paracrine role.

Neuropeptide Y (NPY) has been shown to decrease insulin secretion from rodent islets. NPY messenger ribonucleic acid (mRNA) has been demonstrated in rat and mouse pancreatic islets. We, therefore, examined human islets for the presence of NPY-encoding mRNA and NPY-like immunoreactivity. Human pancreatic islets were obtained from cadaveric organ donors, using collagenase digestion and purification on BSA density gradients. Northern blot analysis, employing a human NPY riboprobe, revealed specific NPY-encoding mRNA in the islet. Compared to the islet, NPY message abundance was 9-fold higher in the caudate nucleus and 2.4-fold higher in the temporal lobe, but it was 75% lower in the adrenal gland. NPY-like immunoreactivity was present at 2.4 +/- 0.3 fmol/microgram protein in acid-ethanol extracts from the islets. On fast protein liquid chromatography with a reverse phase column, the majority of NPY-like immunoreactivity eluted as a peak with a retention time identical to that of porcine NPY standard. Added NPY (100 nmol/L) decreased (P = 0.001) glucose-stimulated (8 mmol/L) insulin release from the human islets by 45% in a perfusion system. Therefore, human islets synthesize substantial amounts of NPY, which could act as an intra-islet paracrine regulator.

Adolescent↗

PubMed1995

Pyroglutamyl-phenylalanyl-proline amide attenuates thyrotropin-releasing hormone-stimulated insulin secretion in perifused rat islets and insulin-secreting clonal beta-cell lines.

TRH immunoreactivity has been detected in the pancreas of man and rat and localized to the islets of Langerhans. We studied the effect of synthetic TRH and the related tripeptide pyroglutamyl-phenylalanyl-proline amide (EFP) on isolated perifused rat islets and the glucose-responsive clonal cell lines HIT-T15 and RIN5AH. TRH at 10 nM potentiated [0.5 +/- 0.1 (control) vs. 0.8 +/- 0.1 (TRH) pmol/10(6) cells per 120 min; mean +/- SEM; n = 6; P < 0.001; n = 15], whereas EFP from 1 nM upwards suppressed glucose-stimulated insulin secretion [0.8 +/- 0.1 (control) vs. 0.5 +/- 0.1 (EFP) pmol/10(6) cells per 120 min; P < 0.001; n = 12) in the cell lines. Further, EFP reversed TRH-stimulated insulin release. Similar responses were observed in perifused isolated rat islets at the tested dose of 1 microM. Gel permeation chromatography of rat adult and neonatal whole pancreas, isolated islets, and HIT cell extracts demonstrated the elution of total TRH-like immunoreactivity (t-TRH-LI) in the same position as synthetic TRH. Cation exchange analysis of the t-TRH-LI from rat adult pancreas and HIT cell extracts showed that neutral TRH-like peptides corresponding to synthetic EFP were also present. Reverse-phase fast protein liquid chromatographic analysis of t-TRH-LI in the unbound fraction of these extracts subjected to anion exchange columns, also demonstrated peaks corresponding to synthetic EFP. We conclude that TRH potentiates, whereas EFP inhibits, glucose-stimulated insulin release in isolated perifused islets and the cell lines. In addition, EFP reversed the stimulatory effect of TRH. The presence of EFP-LI in rat adult and neonatal pancreas and HIT cell extracts suggests it may contribute in the modulation of pancreatic endocrine function.

Amino Acid Sequence↗

PubMed1994

Amylin tonally regulates arginine-stimulated insulin secretion in rats.

To assess the effect of naturally-present amylin in the control of insulin release we infused a novel amylin antagonist, its 8-37 fragment, or amylin in anaesthetized rats for 60 min, and 30 min after the start arginine was infused for 14 min. Amylin8-37 decreased the blood glucose concentration by 18% whereas the plasma insulin concentration was 90% higher following arginine treatment. In contrast amylin infusion raised both glucose and insulin concentrations. These results suggest that while amylin added at high dose can induce peripheral insulin resistance, naturally present amylin tonally controls insulin secretion.

Amyloid↗

PubMed1994

Lack of acute effect of amylin (islet associated polypeptide) on insulin sensitivity during hyperinsulinaemic euglycaemic clamp in humans.

It is suggested that amylin (islet associated polypeptide), co-secreted with insulin from the pancreatic beta cells acts as a circulating hormone which opposes the action of insulin on muscle and increases hepatic glucose production. We have tested the effect of amylin in human subjects on postabsorptive glucose homeostasis and on insulin sensitivity using the euglycaemic hyperinsulinaemic clamp. The amylin used opposed insulin-mediated glucose disposal in rat soleus muscle at concentrations of 10 nmol/l. Seven subjects were studied on two occasions and infused with either amylin or placebo for 6 h, initially when postabsorptive and then during a euglycaemic hyperinsulinaemic clamp. Mean plasma amylin concentrations during the first 3 h were 2006 +/- 327 pmol/l during amylin infusion and 20 +/- 9 pmol/l during the control infusion. Amylin infusion had no effect on postabsorptive plasma concentrations of insulin (control: 32 +/- 16 vs amylin: 25 +/- 8 pmol/l) or glucose (5.1 +/- 0.1 vs 5.3 +/- 0.1 mmol/l). During the clamp, amylin concentrations were 1636 +/- 422 pmol/l when it was infused and 24 +/- 6 during control infusions. Plasma glucose and insulin concentrations were well matched during the control and amylin infusions (glucose: 4.7 +/- 0.1 vs 4.8 +/- 0.1 mmol/l; insulin: 198 +/- 37 vs 195 +/- 22 pmol/l). Exogenous glucose infusion rates were a mean of 13% lower than control values during the amylin infusion but were not statistically different (p = 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Long-acting somatostatin analogue therapy and protein metabolism in patients with jejunostomies.

BACKGROUND/AIMS: Previous studies have shown that secretory losses in patients with end jejunostomy syndrome (EJS) on home parenteral nutrition (HPN) can be suppressed by the somatostatin analogue, octreotide, thus facilitating fluid balance. However, the hormone also has antianabolic actions that may interfere with the use of infused amino acids. METHODS: Amino acid metabolism, pancreatic enzyme synthesis and secretion, and mucosal protein turnover were measured by primed/continuous intravenous infusion of [1-14C] leucine tracer, duodenal aspiration, and endoscopic mucosal biopsy techniques during hormonal stimulation with pentagastrin and cholecystokinin 8. RESULTS: In comparison with normal healthy controls, baseline measurements of amino acid metabolism were normal in patients with EJS/HPN, but pancreatic enzyme synthesis and secretion were elevated. Octreotide therapy improved fluid balance but suppressed gut hormone (insulin, gastrin, glucagon, peptide YY) levels in blood and the uptake of amino acids into pancreatic enzyme and mucosal proteins, increasing oxidative losses. CONCLUSIONS: Octreotide improves fluid balance in patients who have undergone jejunostomy but reduces the use of amino acids for splanchnic protein synthesis. This may interfere with the physiological process of adaptation to intestinal resection.

Adult↗

PubMed1994

Islet amyloid polypeptide: does it play a pathophysiological role in the development of diabetes?

There is suggestive evidence that amylin acts physiologically in an autocrine manner within the islet to restrain insulin secretion, but conversely there is little indication that this action of amylin plays any role in the development of NIDDM. Deposition of amylin within pancreatic islets is a feature in patients with NIDDM but is of sufficient degree to disrupt beta-cell function in only a small minority of individuals. Current evidence suggests that amylin does not have any physiologically important extra-islet metabolic effects. The potential exists for the development of amylin antagonists as pharmacological agents to enhance insulin secretion in NIDDM but antagonism of systematic CGRP would need to be avoided. There is little, if any, indication that either replacement of amylin or treatment with amylin agonists are likely to have any beneficial role in patients with IDDM.

Amyloid↗

PubMed1994

Pancreatic enzyme synthesis and turnover in human subjects.

Animal studies have shown that pancreatic enzyme secretion is independent of enzyme synthesis. To investigate this relationship in humans, we have coinfused 14C-labeled leucine tracer with cholecystokinin octapeptide in nine healthy adults for 4 h and measured the rate of appearance of secreted and newly labeled enzymes in the duodenum. Enzyme secretion was well maintained throughout, but newly labeled enzymes only appeared in juice between 75 and 101 min (median time, 86 min), indicating that initial secretion was dependent on the release of zymogen stores and that the median production time for new enzymes was 86 min. Between 85 and 225 min there was a curvilinear increase in the enrichment of secreted enzymes with newly synthesized enzymes, suggesting a median turnover rate of zymogen stores of 29%/h (range 12-47%/h). In conclusion, our results suggest that in healthy humans, postprandial pancreatic enzyme secretion is maintained by the export of a large stored pool and is not rate limited by enzyme synthesis, since it takes approximately 86 min for newly synthesized enzymes to take part in the digestive process.

Adult↗

PubMed1994

Evidence of a paracrine role of neuropeptide-Y in the regulation of insulin release from pancreatic islets of normal and dexamethasone-treated rats.

Recent evidence suggests that a number of a paracrine regulatory peptides, including neuropeptide-Y (NPY), are synthesized within pancreatic islets. We have, therefore, assessed the role of NPY on insulin release from isolated perifused rat islets. NPY release was detectable at 2.1 (95% confidence interval, 1.6-2.6) attomoles/islet.min from the perifused islets of control rats when the glucose concentration was 2.8 mM and decreased by 62% (P = 0.01) on changing to 20 mM glucose. The initial insulin release was 0.7 (0.3-1.6) fmol/islet.min, and it was increased 4-fold (P < 0.001) by high glucose. Simultaneously, pancreatic glucagon release was decreased 85% (P < 0.001), and somatostatin release was decreased 25% (P = 0.06). In contrast, in islets from rats given dexamethasone (4 mg/kg.day) for 10 days, NPY release was 6-fold increased by high glucose. NPY (100 nM) decreased insulin release by 44% (P < 0.001). To determine the influence of naturally present islet NPY on insulin release, immunoneutralization with NPY antiserum was employed. With control rat islets, insulin release was increased 3-fold with NPY antiserum (P = 0.02) in the presence of 2.8 mM glucose and elevated 2-fold at 8 mM glucose (P < 0.001). NPY immunoneutralization similarly increased insulin release from the perifused islets of rats treated with dexamethasone. Our results suggest that NPY is produced by pancreatic islets, and its expression is dependent on the prevailing endocrine environment. Islet NPY appears to constrain insulin release under a variety of conditions. NPY may be an important intraislet paracrine hormone.

Animals↗

PubMed1993

Comparison of precursor pools with leucine, alpha-ketoisocaproate, and phenylalanine tracers used to measure splanchnic protein synthesis in man.

Relationships were determined between the labeling of leucine and phenylalanine at the intracellular site of protein synthesis in the pancreas and labeling of plasma leucine, its keto acid, alpha-ketoisocaproate (KIC), and phenylalanine. Six healthy subjects were studied for 480 minutes during a primed constant infusion of [1-14C]leucine, and six healthy subjects were studied for 240 minutes with [1-14C]leucine, [4,5-3H]phenylalanine, and [1-13C]KIC. An oro-duodenal tube was placed and pancreatic exocrine fluid was sampled by duodenal aspiration during cholecystokinin stimulation. During the 480-minute study, in the final 120 minutes the specific activity (SA) of enzyme leucine (3.14 +/- 0.27 dpm/nmol) was lower than that of plasma leucine (4.18 +/- 0.30 dpm/nmol, P < .001), but was not different from that of plasma KIC (3.02 +/- 0.18 dpm/nmol). During the 240-minute study, protein synthesis rates of secreted pancreatic enzymes when calculated with [3H]phenylalanine were lower (P = .006) by 28% +/- 2% than rates based on [14C]KIC SA, and lower (P = .004) by 16% +/- 3% than those calculated using [14C]leucine SA. Incorporation of [13C]leucine into pancreatic enzymes was not different from that of [14C]leucine when [13C]leucine and [14C]KIC, respectively, were used to denote precursor labeling. The results indicate that plasma KIC SA reflects the precursor pool for pancreatic protein synthesis during leucine tracer infusion, and plasma leucine enrichment also reflects the precursor pool when [1-13C]KIC is infused in man. The precursor pool is erroneously overestimated when using plasma SA of [4,5-3H]phenylalanine or [1-14C]leucine.

Adult↗

PubMed1993

Tritium and 14C isotope effects using tracers of leucine and alpha-ketoisocaproate.

To test if different leucine tracers behave in an indistinguishable manner and, by implication, that their metabolism is identical to that of natural leucine, we measured whole body leucine turnover in dogs and humans and fibrinogen synthesis in dogs by simultaneously infusing either [1-14C]leucine or [4,5-3H]leucine or [1-14C]alpha-ketoisocaproate (KIC) and [4,5-3H]KIC. Whole body leucine fluxes calculated from the plasma specific activity of the transaminated product of the infused tracer (reciprocal pool model) were lower (dogs by 5.7%; humans by 6.4%, both P < 0.02) when the plasma 3H specific activity compared to 14C specific activity were used with leucine tracers and were also lower (dogs by 4.4%, P < 0.02; humans by 8.6%, P < 0.06) using the KIC tracers. Using leucine or KIC tracers in dogs, the fractional rate of fibrinogen synthesis was 6.7% or 9.4% lower, respectively, (P < 0.02) using the 3H versus the 14C tracer. The apparently lower incorporation of 3H into protein was only in part accounted for by detritiation (2.1%, P = 0.05) of [3H]leucine during acid hydrolysis of proteins. These results suggest that in vivo and/or in vitro differential isotope effects are small (approximately 5%), but should be considered when dual isotopes infusions are employed to partition amino acid metabolism.

Animals↗

PubMed1993

Influence of islet amyloid polypeptide and the 8-37 fragment of islet amyloid polypeptide on insulin release from perifused rat islets.

IAPP, or amylin, is a 37-amino acid peptide that is co-secreted with insulin from the pancreatic beta-cells. We have determined the effects of IAPP and the antagonist 8-37 fragment of IAPP on the secretion of insulin from isolated rat islets studied in a perifusion system. Insulin secretion was stimulated by 8 mM glucose and 0.2 microM carbachol. IAPP at 10(-7) M reduced insulin release by 32% from 7.1 (95% Cl 5.8-8.6) to 4.8 (3.0-7.5) fmol.min-1 x islet-1 (P = 0.046, n = 7). IAPP at 1.5 x 10(-6) M reduced insulin release by 62% from 6.5 (3.4-12.3) to 2.5 (1.4-4.4) fmol.min-1 x islet-1 (P = 0.001, n = 6). IAPP at 10(-5) M decreased insulin release by 70% (P < 0.001, n = 6). When IAPP (8-37) at 10(-5) M was added to IAPP at 1.5 x 10(-6) M, there was only a 22% reduction of insulin release (P = 0.06, n = 6) compared with control chambers with no peptide added. This reduction was less (P = 0.002) than observed with IAPP (1.5 x 10(-6) M) alone. IAPP (8-37) at 4 x 10(-5) M in the absence of exogenously added IAPP increased insulin secretion by 48% (P = 0.01, n = 6), but IAPP (8-37) at 10(-5) M did not alter insulin secretion. These findings demonstrate that IAPP decreases insulin secretion from islet beta-cells, an effect that can be antagonized by the 8-37 fragment of IAPP.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid↗

PubMed1992

Clinical studies with the beta-adrenoceptor agonist BRL 26830A.

BRL 26830A is a beta-adrenoceptor agonist drug that shows a high degree of selectivity for thermogenesis and has potential as an antiobesity agent. We undertook a double-blind trial in 40 obese subjects who received either BRL 26830A or placebo for 18 wk. All were prescribed a 3.35 MJ (800 kcal) diet. Weight loss was 15.4 +/- 6.6 (SD) kg on BRL 26830A compared with 10.0 +/- 5.9 kg on placebo (P less than 0.02). The relative weight losses were 0.93% and 0.61%/wk, respectively. Urinary nitrogen excretion was similar in both groups and skinfold measurements indicated a 4-kg difference in fat lost, suggesting that weight loss was mainly from adipose tissue. Psychological assessments showed that BRL 26830A had no adverse effect on mood and no effect on hunger or satiety. Tremor was experienced by 12 of 16 treated subjects who completed the study. It was generally rated as mild, occurred 1 h after dosing, and tended to diminish with time on treatment. Subsequent analysis of the tremor suggested that it is an exaggeration of physiological tremor mediated through skeletal muscle beta 2 adrenoceptors.

Adrenergic beta-Agonists↗

PubMed1992

Growth hormone and lean tissue catabolism during long-term glucocorticoid treatment.

OBJECTIVES: The aim of the study was to determine whether growth hormone (GH) treatment decreased net protein catabolism of lean tissues in patients receiving chronic glucocorticoid treatment. DESIGN: Whole body leucine kinetics were measured in post-absorptive conditions using a 1-14C-leucine infusion before and during GH administration (0.0125 mg/kg/day; 0.033 U/kg/day) for 7 days. PATIENTS: We studied four patients (age range 31-71 years) who had taken prednisone (mean +/- SEM 0.21 +/- 0.03 mg/kg/day, total dose 10-27.5 mg/day) for longer than 5 months for various lung diseases. RESULTS: During GH treatment leucine oxidation decreased (baseline 0.44 +/- 0.07 vs GH 0.37 +/- 0.05 mumol/kg lean body mass/min, P = 0.01) and non-oxidative leucine disposal increased (1.95 +/- 0.10 vs 2.05 +/- 0.09 mumol/kg lean body mass/min, P = 0.02) but leucine appearance was unaltered. CONCLUSIONS: We conclude that GH decreased amino acid catabolism and improved protein synthesis without altering protein breakdown in patients receiving chronic glucocorticoid treatment. There may be a role for GH in mitigating the protein catabolic side-effects of prolonged glucocorticoid treatment.

Body Composition↗

PubMed1992

Expression of messenger ribonucleic acids encoding neuropeptide-Y, substance-P, and vasoactive intestinal polypeptide in human pituitary.

The local production of autocrine or paracrine agents in endocrine tissues represents an important level of hormonal regulation. The synthesis of neuropeptide-Y (NPY), substance-P (SP), and vasoactive intestinal peptide (VIP) in the rat anterior pituitary gland has been well demonstrated. We have now studied their expression in human postmortem pituitary tissue. Northern blot analysis of poly(A)+ RNA from whole human pituitaries revealed mRNA encoding the precursors for NPY, SP, and VIP whose hybridization characteristics were indistinguishable from those of the same mRNAs described in previously characterized human tissues. VIP mRNA was detectable in all samples tested, with NPY and preprotachykinin-A mRNA (which encodes SP) detectable in a subset of the pituitaries. The concentration of immunoreactive NPY in whole human pituitary was 3.8 +/- 1.1 pmol/g wet wt in males and 2.9 +/- 0.5 pmol/g wet wt in females (mean +/- SEM; n = 10), that of SP was 3.1 +/- 0.4 pmol/g wet wt in males and 5.2 +/- 1.3 pmol/g wet wt in females (n = 10), and that of VIP was 8.1 +/- 2.9 pmol/g wet wt in males and 5.3 +/- 1.6 pmol/g wet wt in females (n = 10). Size-fractionation of pituitary extracts by gel permeation chromatography revealed single peaks of NPY and VIP-like immunoreactivity in the positions of the standards, while SP-like immunoreactivity mostly eluted in the position of synthetic SP, with two minor immunoreactive peaks eluting earlier. The low levels of NPY, SP, and VIP and their mRNAs in the human pituitary are consistent with peptides having an autocrine/paracrine, rather than endocrine, mode of action.

Adult↗

PubMed1992

Metabolic effects of three weeks administration of the beta-adrenoceptor agonist BRL 26830A.

BRL 26830A is a thermogenic beta-adrenergic agonist drug which has an anti-obesity effect in animals and diet-restricted obese man. This study was undertaken in obese subjects who were not calorie restricted to assess the effect of three weeks drug administration on energy expenditure and glucose, amino acid and fatty acid metabolism in the post-absorptive and fed states. Stable isotope tracers were employed to determine kinetic data both at baseline and during adrenaline infusion. There was no evidence of BRL 26830A causing a major shift in fuel metabolism or having an anabolic effect. Baseline plasma concentrations of glycerol (P less than 0.01) and palmitate (P less than 0.01) were reduced, glucose remained within the normal range, whereas insulin decreased after BRL 26830A. The hypoaminoacidaemic effect of adrenaline was attenuated by BRL 26830A (P less than 0.01 for branched-chain amino acids, P less than 0.05 for total amino acids). The results suggest that BRL 26830A improves insulin sensitivity and causes selective down-regulation of adrenergic receptors. The increased insulin sensitivity may be a useful therapeutic effect for this class of drug and suggests a possible role in the treatment of obese non-insulin dependent diabetic patients.

Adrenergic beta-Agonists↗

PubMed1991

Effect of adrenaline infusion on fatty acid and glucose turnover in lean and obese human subjects in the post-absorptive and fed states.

1. Energy expenditure, plasma glucose and palmitate kinetics and leg glycerol release were determined simultaneously both before and during adrenaline infusion in lean and obese human subjects. Seven lean subjects (mean 96.5% of ideal body weight) were studied in the post-absorptive state and also during mixed nutrient liquid feeding, eight obese subjects (mean 165% of ideal body weight) were studied in the post-absorptive state and six obese subjects (mean 174% of ideal body weight) were studied during feeding. 2. Resting energy expenditure was higher in the obese subjects, but the thermic response to adrenaline, both in absolute and percentage terms, was similar in lean and obese subjects. Plasma adrenaline concentrations attained (3 nmol/l) were comparable in all groups and the infusion had no differential effects on the plasma insulin concentration. Before adrenaline infusion the plasma glucose flux was higher in the obese than in the lean subjects in the fed state only (45.8 +/- 3.8 versus 36.6 +/- 1.0 mmol/h, P less than 0.05); it increased to the same extent in both groups with the adrenaline infusion. 3. Before the adrenaline infusion plasma palmitate flux was higher in the obese than in the lean subjects (by 51%, P less than 0.01, in the post-absorptive state and by 78%, P less than 0.05, in the fed state). However, there was no significant change during adrenaline infusion in the obese subjects (from 13.5 +/- 1.00 to 15.0 +/- 1.84 mmol/h, not significant, in the post-absorptive state and from 14.4 +/- 2.13 to 15.7 +/- 1.74 mmol/h, not significant, in the fed state), whereas there were increases in the lean subjects (from 8.93 +/- 1.10 to 11.2 +/- 1.19 mmol/h, P less than 0.05, in the post-absorptive state, and from 8.06 +/- 1.19 to 9.86 +/- 0.93 mmol/h, P less than 0.05, in the fed state). 4. Before adrenaline infusion the palmitate oxidation rate was also higher in the obese than in the lean subjects (1.86 +/- 0.14 versus 1.22 +/- 0.09 mmol/h, P less than 0.01, in the post-absorptive state and 1.73 +/- 0.25 versus 1.12 +/- 0.12 mmol/h, P less than 0.05, in the fed state). However, in response to adrenaline the fractional oxidation rate (% of flux) increased less in the obese than in the lean subjects, especially in the post-absorptive state (from 13.8 +/- 1.02 to 14.9 +/- 1.39%, not significant, versus from 13.7 +/- 0.98 to 19.3 +/- 1.92%, P less than 0.05). These effects were independent of feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗