β-Adrenergic blockade counteracts starvational ketosis, but aggravates post-exercise ketosis in non-athletes

1988 ◽  
Vol 119 (1) ◽  
pp. 167-171 ◽  
Author(s):  
Y. A. K. Vahed ◽  
J. H. Koeslag ◽  
J. de V. Lochner

ABSTRACT Post-exercise ketosis is not abolished by glucose ingestion immediately after exercise but is counteracted by simultaneous β-adrenergic blockade. To investigate the effect of β-adrenergic blockade on post-exercise ketosis without the ingestion of glucose, we administered propranolol (1 mg/kg body mass) to 15 carbohydrate-starved people, of whom five had just walked 9 km in 2 h. There were 43 control subjects (no propranolol). The blood concentration of 3-hydroxybutyrate rose from 0·18 ± 0·02 (s.e.m.) mmol/l at 07.00 h to 0·35 ±0 04 mmol/l at 09.00 h whether the subjects had exercised during those 2 h or not (d.f. = 57). The blood concentration of 3-hydroxybutyrate at 15.00 h in the groups not treated with propranolol was not affected by exercise (0·95 ± 0·90 mmol/l; d.f. = 42). Propranolol significantly raised the concentration of 3-hydroxybutyrate at 15.00 h to 1·68 ±0·26 mmol/l when given after exercise (d.f. = 4), but lowered it to 0·46 ±0·07 mmol/l in the non-exercised group (d.f. = 9). This was not accompanied by significant differences in the blood concentrations of glucose, free fatty acid, insulin or glucagon. The difference in response to propranolol administration is probably determined by the alanine and lactate flux from muscle for hepatic oxaloacetate synthesis. J. Endocr. (1988) 119, 167–171

1994 ◽  
Vol 266 (6) ◽  
pp. E914-E920 ◽  
Author(s):  
M. D. Jensen ◽  
M. L. Martin ◽  
P. E. Cryer ◽  
L. R. Roust

To determine whether estrogen directly affects effective adipose lipolysis, palmitate rate of appearances ([14C]palmitate) was measured in 15 postmenopausal women. Each volunteer was studied after > or = 2 mo of estrogen treatment and again after > or = 2 mo of estrogen deficiency. Plasma hormone concentrations were controlled and identical on the 2 study days with use of the pancreatic clamp technique, and the lipolytic response to epinephrine and epinephrine + phentolamine was assessed. Results showed that overall palmitate flux was greater (10-20%, P < 0.05) during the estrogen-deficient than during the estrogen-replete study. Adrenergic stimulation of lipolysis was not specifically influenced by estrogen treatment, and control of plasma hormone concentrations did not eliminate the difference in palmitate flux between the estrogen-deficient and estrogen-replete study days. We conclude that estrogen deficiency is associated with increased plasma free fatty acid availability and that estrogen likely has direct, albeit small, effects on adipose tissue lipolysis.


2002 ◽  
Vol 283 (2) ◽  
pp. E346-E352 ◽  
Author(s):  
Mandeep Bajaj ◽  
Rachele Berria ◽  
Thongchai Pratipanawatr ◽  
Sangeeta Kashyap ◽  
Wilailak Pratipanawatr ◽  
...  

To investigate the effect of elevated plasma free fatty acid (FFA) concentrations on splanchnic glucose uptake (SGU), we measured SGU in nine healthy subjects (age, 44 ± 4 yr; body mass index, 27.4 ± 1.2 kg/m2; fasting plasma glucose, 5.2 ± 0.1 mmol/l) during an Intralipid-heparin (LIP) infusion and during a saline (Sal) infusion. SGU was estimated by the oral glucose load (OGL)-insulin clamp method: subjects received a 7-h euglycemic insulin (100 mU · m−2 · min−1) clamp, and a 75-g OGL was ingested 3 h after the insulin clamp was started. After glucose ingestion, the steady-state glucose infusion rate (GIR) during the insulin clamp was decreased to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in GIR during the period after glucose ingestion from the ingested glucose load. [3-3H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of endogenous glucose production (EGP) and glucose disappearance (Rd). During the 3-h euglycemic insulin clamp before glucose ingestion, Rd was decreased (8.8 ± 0.5 vs. 7.6 ± 0.5 mg · kg−1 · min−1, P < 0.01), and suppression of EGP was impaired (0.2 ± 0.04 vs. 0.07 ± 0.03 mg · kg−1 · min−1, P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly increased during the LIP vs. Sal infusion study (30 ± 2 vs. 20 ± 2%, P < 0.005). In conclusion, an elevation in plasma FFA concentration impairs whole body glucose Rd and insulin-mediated suppression of EGP in healthy subjects but augments SGU.


1984 ◽  
Vol 247 (6) ◽  
pp. E756-E764 ◽  
Author(s):  
J. H. Shaw ◽  
R. R. Wolfe

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.


2005 ◽  
Vol 15 (4) ◽  
pp. 333-349 ◽  
Author(s):  
Emma Stevenson ◽  
Clyde Williams ◽  
Gareth McComb ◽  
Christopher Oram

This study examined the effects of the glycemic index (GI) of post-exercise carbohydrate (CHO) intake on endurance capacity the following day. Nine active males participated in 2 trials. On day 1, subjects ran for 90 min at 70% VO2max (R1). Thereafter, they were supplied with either a high GI (HGI) or low GI (LGI) CHO diet which provided 8 g CHO/kg body mass (BM). On day 2, after an overnight fast, subjects ran to exhaustion at 70% VO2max (R2). Time to exhaustion during R2 was longer in the LGI trial (108.9 ± 7.4 min) than in the HGI trial (96.9 ± 4.8 min) (P < 0.05). Fat oxidation rates and free fatty acid concentrations were higher in the LGI trial than the HGI trial (P < 0.05). The results suggest that the increased endurance capacity was largely a consequence of the increased fat oxidation following the LGI recovery diet.


1994 ◽  
Vol 266 (3) ◽  
pp. E501-E509 ◽  
Author(s):  
R. C. Bonadonna ◽  
L. C. Groop ◽  
D. C. Simonson ◽  
R. A. DeFronzo

We assessed insulin effects on plasma free fatty acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and body mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs. 20.4 +/- 3.5% in young, P < 0.05), by performing sequential euglycemic clamps at five insulin doses (0.6, 1.5, 3, 6, and 15 pmol.min-1.kg-1) in combination with indirect calorimetry and [1-14C]palmitate plus [3-3H]glucose infusion. At baseline, plasma FFA concentration, turnover infusion. At baseline, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were all increased in the elderly (897 +/- 107 vs. 412 +/- 50 mumol/l and 11.2 +/- 1.4 vs. 5.14 +/- 0.86, 3.45 +/- 0.65 vs. 1.37 +/- 0.25, and 4.63 +/- 0.72 vs. 3.01 +/- 0.33 mumol.min-1.kg-1 lean body mass, P < 0.05 for all comparisons), whereas glucose turnover was similar as a result of decreased glucose oxidation (8.2 +/- 1.4 vs. 13 +/- 1.9 mumol.min-1.kg-1 lean body mass, P < 0.05) and increased glucose storage (6.6 +/- 1.4 vs. 1.7 +/- 1.3 mmol.min-1.kg-1 lean body mass, P < 0.05). At all insulin infusions, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were higher in the elderly than in the younger group (P < 0.05). However, if normalized per fat mass, all FFA and lipid metabolic fluxes, both in the postabsorptive state and during hyperinsulinemia, were comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)


2012 ◽  
Vol 97 (8) ◽  
pp. 2890-2897 ◽  
Author(s):  
Lisa S. Chow ◽  
Elizabeth R. Seaquist ◽  
Lynn E. Eberly ◽  
Mara T. Mashek ◽  
Jill M. Schimke ◽  
...  

Abstract Context: Both training and normal body mass index are associated with high insulin sensitivity, but the mechanism may be different. Objective: The aim of the study was to examine whether lean trained humans may be protected from acute free fatty acid (FFA)-induced insulin resistance compared with lean sedentary humans. Design and Setting: We conducted an interventional trial using either a 6-h lipid (20% Intralipid at 90 ml/h) or glycerol (2.25 g/100 ml at 90 ml/h) infusion along with a concurrent hyperinsulinemic-euglycemic clamp and serial muscle biopsies (0, 120, 360 min) at a clinical research unit at the University of Minnesota. Patients or Participants: The study included lean endurance-trained (n = 14) and sedentary (n = 14) individuals matched for age, gender, and body mass index. Main Outcome Measures: We measured the decline in glucose infusion rate (GIR) during the hyperinsulinemic-euglycemic clamp. Results: The trained group had higher baseline mitochondrial DNA copy number, mRNA of cytochrome C oxidase subunit 3, and insulin sensitivity (as measured by GIR) compared with the sedentary group. When FFA was acutely elevated to the upper physiological range (0.6–0.7 mEq/liter) by lipid infusion, the GIR in both activity groups declined similarly compared with their respective glycerol controls, although insulin signaling, as measured by Ser 473 pAKT/AKT, remained comparable. Specific to the trained group, the stimulatory effect of hyperinsulinemia on mitochondrial mRNA levels during the glycerol infusion was absent during the lipid infusion. Conclusions: Elevated FFA had similar effects in reducing insulin sensitivity in trained and sedentary humans. In trained participants, this decline was associated with alterations in the skeletal muscle mitochondrial mRNA response to hyperinsulinemia.


1978 ◽  
Vol 88 (3) ◽  
pp. 535-544 ◽  
Author(s):  
J. W. Blum ◽  
A. Guillebeau ◽  
U. Binswanger ◽  
P. Kunz ◽  
M. Da Prada ◽  
...  

ABSTRACT Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect.


1967 ◽  
Vol 12 (6) ◽  
pp. 539-548 ◽  
Author(s):  
John M. Cleghorn ◽  
G. Peterfy ◽  
E. J. Pinter ◽  
C. J. Pattee

Infusion of adrenaline or noradrenaline in man gives rise to increases in plasma free fatty acid level through its indirect action on adipose tissue. Many kinds of psychological stresses have been shown to produce elevated plasma FFA levels. The present work aims to delineate some of the psychological and neurohumoral factors which mediate the external stress which leads to fat mobilization. In 18 subjects FFA increase following stress was found to be due to a primary increase in FFA production rather than to diminished use. The effect of emotional stress on this phenomenon was found to be significantly less in the presence of beta adrenergic blockade (propanolol). Thus it was concluded that, a) the adipokinetic mechanism of short-term emotional arousal depends on endogenous catecholamine and, b) FFA mobilization under these circumstances is an indirect measure of catecholamine activity. In two groups of 20 and 24 subjects levels of anxiety and three kinds of hostility were measured from unprompted verbalizations while blood was drawn for FFA determinations. FFA levels were found repeatedly to be positively and significantly correlated with anxiety levels, but not with hostility levels. Maximum FFA levels were found to develop 15 minutes after experimental stress. Even when greater amounts of hostility were provoked by stress interviews, no association between hostility and FFA level was found. The changes in FFA level in REM sleep were also found to be correlated positively and significantly with anxiety levels in 20 dream reports. Further studies were done on nine subjects from whom blood was drawn for plasma free fatty acid determinations while they were asked under hypnosis to assume alternately a passive and an active approach to a task. In experiments in which the subject was instructed to be passive or active, much greater fat mobilization resulted than in experiments in which he was given no suggestion. The passive attitude stimulated somewhat more anxiety. With the suggestion to be passive and no suggestion, anxiety and FFA ceased to co-vary in the time lag relationship described above. The significance of these findings for our beginning understanding of psycho-physiological mechanisms in diabetes mellitus, coronary disease and obesity were mentioned.


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