| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-adrenergic receptor blockade in humans
Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada N1G 2W1
 |
ABSTRACT |
|---|
 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
The caffeine-induced impairment of insulin action is commonly attributed to adenosine receptor (AR) antagonism in skeletal muscle. However, epinephrine, a potent inhibitor of insulin actions, is increased after caffeine ingestion. We tested the hypothesis that the insulin antagonistic effects of caffeine are mediated by epinephrine, and not by AR antagonism, in seven healthy men. On four separate occasions, they received 1) dextrose (placebo, PL), 2) 5 mg/kg caffeine (CAF), 3) 80 mg of propranolol (PR), and 4) 5 mg/kg caffeine + 80 mg of propranolol (CAF + PR) before an oral glucose tolerance test (OGTT). Blood glucose was similar among trials before and during the OGTT. Plasma epinephrine was elevated (P < 0.05) in CAF and CAF + PR. Areas under the insulin and C-peptide curves were 42 and 39% greater (P < 0.05), respectively, in CAF than in PL, PR, and CAF + PR. In the presence of propranolol (CAF + PR), these responses were similar to PL and PR. These data suggest that the insulin antagonistic effects of caffeine in vivo are mediated by elevated epinephrine rather than by peripheral AR antagonism.
methylxanthines; epinephrine; insulin; adenosine; propranolol
| |
INTRODUCTION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
THE TRIMETHYLXANTHINE CAFFEINE has been shown to inhibit insulin-stimulated glucose uptake in isolated adipocytes (31) and in perfused contracting hindlimb (35). In humans, caffeine decreases glucose tolerance (12) and whole body glucose disposal (14, 19, 33) and reduces glucose uptake in skeletal muscle (33) during a euglycemic-hyperinsulinemic clamp. A common mechanism by which caffeine elicits its responses is adenosine receptor antagonism (5, 10). Indeed, findings from in vitro rodent models suggest that caffeine mediated its inhibitory effects on glucose transport by antagonism at the adenosine A1 receptor (31, 35). On the basis of these in vitro studies, it has been proposed that caffeine reduces insulin sensitivity and glucose tolerance in vivo by a similar mechanism of action (12, 14). Moreover, the doses of caffeine administered to the human volunteers in these studies would elicit a plasma caffeine concentration of ~30-45 µM (13, 14), which approaches the inhibition constant of 40-44 µM for adenosine receptors (5, 10), suggesting that caffeine is a strong competitor for binding to adenosine receptors.
However, caffeine has consistently been shown to stimulate epinephrine
release in vivo (13, 14, 33) by increasing adrenal medullary secretion in response to direct stimulation
(9) or indirectly by increasing central stimulation,
causing increased sympathetic outflow (11). A large body
of evidence shows that epinephrine, by activating the 
-adrenergic
receptor, counteracts insulin stimulation of whole body glucose
metabolism (2, 3, 8, 22). In skeletal muscle, epinephrine
has been reported to inhibit insulin-stimulated glucose transport
(6, 16) and reduce glucose uptake by increasing glucose
6-phosphate, an inhibitor of hexokinase (1, 7, 24). Thus
the negative effects associated with caffeine ingestion on insulin
sensitivity and glucose tolerance could theoretically be mediated by
epinephrine, and not by adenosine receptor antagonism. We tested this
hypothesis by administering caffeine in the presence and absence of a
nonselective -adrenergic receptor blocker, propranolol, to seven
healthy men during an oral glucose tolerance test (OGTT).
| |
METHODS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Subjects.
Seven healthy, active men (24 ± 1 yr, 76 ± 4 kg body wt,
23 ± 1 kg/m2 body mass index) were recruited to
participate in the study, which was approved by the University of
Guelph Human Ethics Committee. Informed, written consent was obtained
from each subject before the experiment. The subjects were instructed
to follow a mixed diet containing 
150 g of carbohydrates, to abstain
from caffeine-containing products and alcohol, and to avoid strenuous
physical activity 2 days before the experiment. The subjects reported
to the laboratory on four separate occasions after an overnight fast.
Experimental protocol.
The subjects rested for 15 min, and a catheter was inserted into an
antecubital vein for blood sampling and was kept patent with a normal
saline drip. A resting blood sample, heart rate (HR), and blood
pressure (BP) were obtained (
105 min), and another blood sample was
obtained 15 min later (90 min). Subsequently, the subjects received 5 mg/kg dextrose (placebo, PL), 5 mg/kg caffeine (CAF), 80 mg of
propranolol (PR), or 5 mg/kg caffeine and 80 mg propranolol (CAF + PR) in a randomized, double-blind fashion. The subjects remained at
rest for 90 min. A blood sample was obtained at 0 min, and a 120-min
OGTT was initiated by ingestion of 75 g of glucose (Trutol). The
amount of dextrose administered in PL is a small percentage (<1%) of
the glucose administered for the OGTT. Resting blood samples were
obtained at 15, 30, 60, 90, and 120 min after the glucose drink. To
provide measures of -blockade, HR and BP were monitored throughout
the OGTT, and the subjects then performed cycling exercise for 2 min at
100-, 150-, and 200-W workloads after the OGTT. HR and rating of
perceived exertion were obtained at the end of each workload.
Analytic procedures.
Blood (~7-10 ml) was collected in a sodium heparin-containing
tube. Whole blood (200 µl) was transferred to an Eppendorf tube and
treated with 1 ml of 0.6 M perchloric acid for glucose, lactate, and
glycerol analyses. The remainder of the blood was treated with 120 µl
of 0.24 M EGTA and reduced glutathione (GSH) for determination of
catecholamines. The catecholamine data are presented for five subjects
because of technical difficulties. After centrifugation, aliquots of
supernatant from the perchloric acid-treated samples and plasma from
EGTA-GSH-treated samples were transferred to Eppendorf tubes and stored
at 20 and 80°C, respectively, until the time of analysis. Another
7-10 ml of blood were collected in a nonheparinized tube for serum
free fatty acid (FFA), insulin, and C-peptide analyses. Blood samples
were allowed to clot at room temperature. Samples were separated by
centrifugation, and serum was transferred to Eppendorf tubes and stored
at 20°C until analysis.
Calculations and statistical analyses.
The areas under the curve for glucose, insulin, and C-peptide
concentrations during the 120-min OGTT
[AUC(0-120 min)] were calculated over 120 min by
using the trapezoidal method. Indexes of whole body insulin sensitivity
during the OGTT were calculated according to the following equation
proposed by Matsuda and DeFronzo (27)
|
| |
RESULTS |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
Basal HR and BP were similar among groups. HR was decreased (P < 0.05) in PR (45 ± 1 beats/min) and CAF + PR (43 ± 3 beats/min) compared with PL (50 ± 2 beats/min) and CAF (49 ± 3 beats/min) during the OGTT. CAF resulted in significantly higher systolic (122 ± 2 mmHg), but not diastolic, BP than PL (113 ± 2 mmHg), PR (108 ± 3 mmHg), and CAF + PR (111 ± 3 mmHg) during the OGTT. There were no differences in diastolic BP among groups (data not shown). During the exercise, the increase in HR was ~50% lower in PR and CAF + PR than in PL and CAF and rating of perceived exertion was significantly greater in PR and CAF + PR than in PL and CAF (data not shown).
Blood glucose was similar among trials at 105 min. In response to an
oral glucose load, blood glucose was significantly increased during the
120-min OGTT in all trials (Fig. 1).
There were no differences in blood glucose before or during the entire
OGTT between trials. Before the OGTT, insulin (Fig.
2) and C-peptide (Fig.
3) were not different between trials.
In response to an oral glucose load, insulin (Fig. 2) and C-peptide
(Fig. 3) concentrations were significantly higher at 15 min and
remained higher (P < 0.05) for the remainder of the
OGTT than basal levels. The insulin (Fig. 2) and C-peptide (Fig. 3)
responses to CAF were greater from 15 to 60 min of OGTT than responses
to PL, PR, and CAF + PR. Insulin and C-peptide were not different
from PL, PR, or CAF + PR for the remainder of the OGTT. No
differences were observed in insulin or C-peptide response to an oral
glucose load in PR and CAF + PR compared with PL. The
AUC(0-120 min) of insulin (Table
1) and C-peptide (Table 1) were greater
in CAF than in PL, PR, and CAF + PR. No differences were observed
in AUC(0-120 min) for insulin and C-peptide between
PL, PR, and CAF + PR (Table 2). The
index of whole body insulin sensitivity was reduced (P < 0.05) after CAF ingestion (8.6 ± 0.6) compared with PL
(11.6 ± 0.8), PR (11.9 ± 0.8), and CAF + PR
(11.1 ± 0.7). No differences were observed in whole body
insulin sensitivity between PL, PR, and CAF + PR.
|
|
|
|
|
FFA (Fig. 4) and glycerol (Fig.
5) were similar at 105 and 90 min
in all four trials. Caffeine ingestion resulted in a significant increase in FFA and glycerol at 0, 15, and 30 min (Figs. 4 and 5). FFA
and glycerol were lower (P < 0.05) in PR at 0 and 15 min than in PL and CAF + PR. FFA and glycerol were similar between PL, PR, and CAF + PR for the remainder of the 120-min OGTT. No differences were observed in FFA and glycerol at any time point between
PL and CAF + PR.
|
|
Plasma epinephrine concentration was significantly elevated after caffeine ingestion (CAF and CAF + PR) compared with PL and PR (Table 2). There were no differences in plasma epinephrine between PL and PR and between CAF and CAF + PR. Plasma norepinephrine concentration was similar between trials (Table 2). There was no effect of an oral glucose load on catecholamine concentrations.
| |
DISCUSSION |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
In the present study, caffeine administered in doses that would elicit plasma caffeine concentration of ~30-45 µM (13, 14) increased insulin response by 42% and reduced whole body insulin sensitivity index by 25%. These findings are in accordance with those previously reported (12, 14, 19, 33). On the basis of our previous finding that reduction in net glucose uptake in skeletal muscle was the major determinant of the caffeine-induced reduction in whole body glucose disposal (33), it is reasonable to speculate that the reduced glucose tolerance after caffeine ingestion in the present study resulted from decreased insulin-dependent glucose clearance in skeletal muscle.
It has been proposed that the mechanism by which caffeine impairs glucose uptake in in vitro experimental models (31, 35) and insulin sensitivity and glucose tolerance in humans (12, 14) is adenosine receptor antagonism. However, caffeine also stimulates epinephrine release (13, 14, 33). Thus the caffeine-induced impairment of insulin actions could be secondary to epinephrine and not to adenosine receptor antagonism. Moreover, although a functional role for adenosine has been shown in isolated adipocytes (18, 21), cardiac muscle (23), and rodent skeletal muscle (15, 35), its role in insulin regulation of glucose transport in humans is unclear because since whole body insulin sensitivity (19) and glucose uptake in the forearm (28) were unaffected by infusion of dipyridamole (an adenosine reuptake inhibitor) and adenosine, respectively. Moreover, the presence in human skeletal muscle of the adenosine A1 receptor, which is proposed to mediate adenosine interaction with insulin, is uncertain (26).
To test the hypothesis that reduction in insulin action in vivo after
caffeine ingestion is mediated by elevated epinephrine levels, and not
by adenosine receptor antagonism, we administered caffeine in the
presence and absence of a -adrenergic receptor blocker, propranolol.
Observation of marked reduction in HR during the OGTT and during
exercise in the propranolol trials is consistent with reduction of
sympathetic tone, suggesting that -blockade was indeed achieved in
this study. When caffeine was administered in combination with
propranolol, despite similar levels of epinephrine and
caffeine, insulin and C-peptide concentrations were comparable to those observed in placebo in response to an oral glucose load, suggesting that the greater insulin response to caffeine was indeed secondary to elevated epinephrine levels. A large body of evidence indicates that elevated epinephrine levels acting via -adrenergic receptors selectively induce whole body insulin resistance by transiently increasing hepatic glucose production and impairing glucose
clearance by skeletal muscle (2, 3, 8, 17, 22). It has
also been found that epinephrine enhances -cell responsitivity to
glucose during an intravenous glucose tolerance test (2).
The enhanced insulin response with caffeine ingestion in the present
study is likely elicited to counter epinephrine's opposing actions on
insulin-stimulated glucose clearance by peripheral tissues and,
possibly, an increase in hepatic glucose output, in an effort to
maintain glucose homeostasis. Thus our data do not support the notion
that the insulin antagonistic effects of caffeine in vivo are mediated
by adenosine receptor antagonism in skeletal muscle. Instead, findings
from the present and previous (33) studies suggest that
the negative effects associated with caffeine ingestion on insulin
action are coupled to increased epinephrine production and its
subsequent inhibition of insulin-mediated glucose uptake in skeletal
muscle. Although we did not assess the effects of epinephrine on
insulin responses per se, the notion that endogenous catecholamines are
implicated in the insulin antagonistic effects of caffeine is supported
by findings that the methylxanthine-induced hyperglycemia (30,
32) and peripheral insulin resistance (30) were
eliminated in adrenalectomized and control rats in the presence of
propranolol (32). Furthermore, because of a lack of
compensatory reactions by epinephrine to increased insulin secretion in
these rodents, they developed lethal hypoglycemia in response to
theophylline (30). Although neither intramuscular glucose
nor glucose 6-phosphate was measured in our study, we previously found
that the caffeine-induced impairment of leg glucose uptake was not
accompanied by changes in muscle glucose or glucose 6-phosphate
(33). Thus epinephrine likely inhibited glucose uptake by
affecting glucose transport, rather than by glucose 6-phosphate
inhibition of hexokinase in skeletal muscle.
It is possible that the higher insulin response to caffeine resulted
from a decrease in insulin clearance, rather than an increase in
insulin secretion, to oppose epinephrine-induced impairment of insulin
action after caffeine ingestion. Similarly, normalization of the
caffeine-induced insulin response in the presence of propranolol could
be secondary to inhibition of insulin secretion or stimulation of
insulin clearance by some nonspecific effects of propranolol. However,
we have found that propranolol, in the absence of caffeine, had no
effect on insulin (Fig. 2) or C-peptide concentrations (Fig. 3), nor
did it alter blood glucose levels (Fig. 1) compared with placebo in
response to an oral glucose challenge. This would suggest that the
effects observed when caffeine and propranolol were present
concomitantly resulted from -adrenergic receptor blockade on
peripheral tissues, rather than from any nonspecific effects of
propranolol. Similarly, C-peptide levels paralleled insulin levels in
response to caffeine in the presence and absence of propranolol. On the
basis of these observations, we can conclude that the greater insulin
response to caffeine in the present study reflects altered insulin
secretion, rather than altered clearance.
Caffeine ingestion resulted in higher circulating FFA (Fig. 5), likely secondary to epinephrine stimulation of lipolysis or via antagonism of the adenosine A1 receptor. The finding that the caffeine-induced rise in circulating FFA was abolished in the presence of propranolol suggests that stimulation of lipolysis after caffeine ingestion resulted from elevated epinephrine levels (Fig. 5). Our data are in agreement with those reported by van Baak and Saris (34), who showed similar reductions in FFA when caffeine was administered in combination with propranolol during exercise. Numerous studies have demonstrated by use of Intralipid and heparin infusion that high circulating FFA inhibits glucose uptake in skeletal muscle during insulin stimulation (20, 29). However, it is unlikely that the inhibitory actions of caffeine on glucose tolerance in our study resulted from high circulating FFA. This conclusion is supported by several findings. Although circulating FFA was higher 90 min after caffeine ingestion and before the OGTT, the increase in insulin response was not observed until 15 min after the oral glucose load. Moreover, after caffeine ingestion, the increase in insulin concentration effectively decreased FFA to the level observed in placebo by 30 min of the OGTT, and yet insulin levels remained significantly higher until 90 min of the OGTT. Similarly, in our previous studies, insulin infusion prevented (14) or decreased (33) the caffeine-induced rise in plasma FFA to that observed in placebo, and, yet, whole body insulin sensitivity (14, 33) and net glucose uptake in skeletal muscle (33) remained significantly lower than with placebo during the euglycemic-hyperinsulinemic clamps.
In summary, we have demonstrated that caffeine reduces glucose
tolerance in healthy men in response to an oral glucose challenge. We
have also provided evidence that caffeine's negative impact on glucose
tolerance was reversed in the presence of a -adrenergic receptor
blocker, propranolol. These data suggest that although caffeine can
exert its inhibitory effects on glucose uptake in vitro by adenosine
receptor antagonism, the insulin antagonistic effects of caffeine in
vivo are mediated by elevated epinephrine levels. The findings from
this study certainly cannot discount the potential role for adenosine
receptor interaction with insulin actions in humans. Rather, our
findings suggest that caffeine may not be an appropriate
pharmacological tool to assess adenosine modulation of insulin actions
on carbohydrate metabolism in vivo in light of the confounding effects
elicited by the concomitant presence of epinephrine, which has profound
counterregulatory effects on insulin's diverse actions in peripheral tissues.
| |
ACKNOWLEDGEMENTS |
|---|
The authors gratefully acknowledge the cooperation of the subjects and the technical assistance provided by P. Sathasivam.
| |
FOOTNOTES |
|---|
Funding for this study was provided by the Natural Science and Engineering Research Council of Canada. F. S. L. Thong was supported by a National Sciences and Engineering Research Council Postgraduate Scholarship, Ontario Graduate Scholarships, and Student Research Awards from the Gatorade Sports Science Institute.
Address for reprint requests and other correspondence: F. S. L. Thong, Dept. of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1 (E-mail: fthong{at}uoguelph.ca).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
First published February 1, 2002;10.1152/japplphysiol.01229.2001
Received 12 December 2001; accepted in final form 21 January 2002.
| |
REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Aslesen, R,
and
Jensen J.
Effects of epinephrine on glucose metabolism in contracting rat skeletal muscles.
Am J Physiol Endocrinol Metab
275:
E448-E456,
1998
2.
Avogaro, A,
Toffolo G,
Valerio A,
and
Cobelli C.
Epinephrine exerts opposite effects on peripheral glucose disposal and glucose-stimulated insulin secretion.
Diabetes
45:
1373-1378,
1996[Abstract].
3.
Baron, AD,
Wallace P,
and
Olefsky JM.
In vivo regulation of non-insulin-mediated and insulin-mediated glucose uptake by epinephrine.
J Clin Endocrinol Metab
64:
889-895,
1987
4.
Bergmeyer, HU,
Bernt E,
Schmidt F,
and
Stork H.
D-Glucose determination with hexokinase and glucose-6-phosphate dehydrogenase.
In: Methods of Enzymatic Analysis, edited by Bergmeyer HU.. New York: Academic, 1974, p. 1196-1201.
5.
Biaggioni, I,
Paul S,
Puckett A,
and
Arzubiaga C.
Caffeine and theophylline as adenosine receptor antagonists in humans.
J Pharmacol Exp Ther
258:
588-593,
1991
6.
Bonen, A,
Megeney LA,
McCarthy SC,
McDermott JC,
and
Tan MH.
Epinephrine administration stimulates GLUT4 translocation but reduces glucose transport in muscle.
Biochem Biophys Res Commun
187:
685-691,
1992[Web of Science][Medline].
7.
Chiasson, JL,
Shikama H,
and
Chu DTW
Inhibitory effect of epinephrine on insulin-stimulated glucose uptake by rat skeletal muscle.
J Clin Invest
68:
706-713,
1981[Web of Science][Medline].
8.
Deibert, DC,
and
DeFronzo RA.
Epinephrine-induced insulin resistance in man.
J Clin Invest
65:
717-721,
1980[Web of Science][Medline].
9.
De Schaepdryver, AF.
Physio-pharmacological effects on suprarenal secretion of adrenaline and noradrenaline in dogs.
Arch Int Pharmacodyn Ther
19:
517-518,
1959.
10.
Fredholm, BB.
Adenosine, adenosine receptors and the actions of caffeine.
Pharmacol Toxicol
76:
93-101,
1998.
11.
Graham, TE,
Helge JW,
Maclean D,
Kiens B,
and
Richter EA.
Caffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exercise.
J Physiol
529:
837-847,
2000
12.
Graham, TE,
Sathasivam P,
Rowland M,
Marko N,
Greer F,
and
Battram D.
Caffeine ingestion elevates plasma insulin response in humans during an oral glucose tolerance test.
Can J Physiol Pharmacol
79:
559-565,
2001[Web of Science][Medline].
13.
Graham, TE,
and
Spriet LL.
Metabolic, catecholamine, and exercise performance responses to various doses of caffeine.
J Appl Physiol
78:
867-874,
1995
14.
Greer, F,
Hudson R,
Ross R,
and
Graham TE.
Caffeine decreases glucose disposal during an euglycemic hyperinsulinemic clamp in sedentary males.
Diabetes
50:
2349-2354,
2001
15.
Han, DH,
Hansen PA,
Nolte LA,
and
Holloszy JO.
Removal of adenosine decreases the responsiveness of muscle glucose transport to insulin and contractions.
Diabetes
47:
1671-1675,
1998[Abstract].
16.
Han, XX,
and
Bonen A.
Epinephrine translocates GLUT-4 but inhibits insulin-stimulated glucose transport in rat muscle.
Am J Physiol Endocrinol Metab
274:
E700-E707,
1998
17.
James, DE,
Burleigh KM,
and
Kraegen EW.
In vivo glucose metabolism in individual tissues of the rat: interaction between epinephrine and insulin.
J Biol Chem
261:
6366-6374,
1986
18.
Joost, HG,
Weber TM,
Cushman SW,
and
Simpson IA.
Insulin-stimulated glucose transport in rat adipose cells.
J Biol Chem
261:
10033-10036,
1986
19.
Keijzers, GB,
De Galan BE,
Tack CJ,
and
Smits P.
Caffeine can decrease insulin sensitivity in humans.
Diabetes Care
25:
364-369,
2002
20.
Kelley, DE,
Mokan M,
Simoneau JA,
and
Mandarino LJ.
Interaction between glucose and free fatty acid metabolism in human skeletal muscle.
J Clin Invest
92:
91-98,
1993[Web of Science][Medline].
21.
Kuroda, M,
Honnor RC,
Cushman SW,
Londos C,
and
Simpson IA.
Regulation of insulin-stimulated glucose transport in the isolated rat adipocyte.
J Biol Chem
262:
245-253,
1987
22.
Laakso, M,
Edelman SV,
Brechtel G,
and
Baron AD.
Effects of epinephrine on insulin-mediated glucose uptake in whole body and leg muscle in humans: role of blood flow.
Am J Physiol Endocrinol Metab
263:
E199-E204,
1992
23.
Law, WR,
McLane MP,
and
Raymond RM.
Adenosine is required for myocardial insulin responsiveness in vivo.
Diabetes
37:
842-845,
1988[Abstract].
24.
Lee, AD,
Hansen PA,
Schluter J,
Gulve EA,
Gao J,
and
Holloszy JO.
Effects of epinephrine on insulin-stimulated glucose uptake and GLUT-4 phosphorylation in muscle.
Am J Physiol Cell Physiol
273:
C1082-C1087,
1997
25.
Lowry, OH,
and
Passonneau JV.
Enzymatic Analysis: A Practical Guide. Totowa, NJ: Humana, 1993.
26.
Lynge, J,
and
Hellsten Y.
Distribution of adenosine A1, A2a, A2b receptors in human skeletal muscle.
Acta Physiol Scand
169:
283-290,
2000[Web of Science][Medline].
27.
Matsuda, M,
and
DeFronzo RA.
Insulin sensitivity indices obtained from oral glucose tolerance testing.
Diabetes Care
22:
1462-1470,
1999
28.
Natali, A,
Bonadonna RC,
Santoro D,
Quiñone Galvan A,
Baldi S,
Frascerra S,
Palombo C,
Ghione S,
and
Ferrannini E.
Insulin resistance and vasodilation in essential hypertension: studies with adenosine.
J Clin Invest
94:
1570-1576,
1994[Web of Science][Medline].
29.
Roden, M,
Price TB,
Perseghin G,
Petersen KR,
Rothman DL,
Cline GW,
and
Shulman GI.
Mechanism of free fatty acid-induced insulin resistance in humans.
J Clin Invest
97:
2859-2865,
1996[Web of Science][Medline].
30.
Sacca, L,
Perez G,
Rengo F,
Pascucci I,
and
Condorelli M.
Effects of theophylline on glucose kinetics in normal and sympathectomized rats.
Diabetes
24:
249-256,
1975[Abstract].
31.
Steinfelder, HJ,
and
Petho-Schramm S.
Methylxanthines inhibit glucose transport in rat adipocytes by two independent mechanisms.
Biochem Pharmacol
40:
1154-1157,
1990[Web of Science][Medline].
32.
Strubelt, O.
The influence of reserpine, propranolol, and adrenal medullectomy on the hyperglycemic action of theophylline and caffeine.
Arch Int Pharmacodyn Ther
179:
215-224,
1969[Web of Science][Medline].
33.
Thong, FSL,
Derave W,
Kiens B,
Graham TE,
Ursø B,
Wojtaszewski JFP,
Hansen BF,
and
Richter EA.
Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise.
Diabetes
51:
583-590,
2002
34.
Van Baak, MA,
and
Saris WHM
The effect of caffeine on endurance performance after nonselective -adrenergic blockade.
Med Sci Sports Exerc
32:
499-503,
2000[Web of Science][Medline].
35.
Vergauwen, L,
Hespel P,
and
Richter EA.
Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.
J Clin Invest
93:
974-981,
1994[Web of Science][Medline].
36.
Weiker, H,
Feraudi M,
Hagele H,
and
Pluto R.
Electrochemical determination of catecholamines in urine and plasma separations with HPLC.
Clin Chem Acta
141:
17-25,
1984[Web of Science][Medline].
This article has been cited by other articles:
|
|
 |
|
  E. Lopez-Garcia, R. M. van Dam, T. Y. Li, F. Rodriguez-Artalejo, and F. B. Hu The Relationship of Coffee Consumption with Mortality Ann Intern Med, June 17, 2008; 148(12): 904 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L Moisey, S. Kacker, A. C Bickerton, L. E Robinson, and T. E Graham Caffeinated coffee consumption impairs blood glucose homeostasis in response to high and low glycemic index meals in healthy men Am. J. Clinical Nutrition, May 1, 2008; 87(5): 1254 - 1261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Lane, M. N. Feinglos, and R. S. Surwit Caffeine Increases Ambulatory Glucose and Postprandial Responses in Coffee Drinkers With Type 2 Diabetes Diabetes Care, February 1, 2008; 31(2): 221 - 222. [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Battram, T. E. Graham, and F. Dela Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans J. Physiol., September 15, 2007; 583(3): 1069 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Battram, J. Bugaresti, J. Gusba, and T. E. Graham Acute caffeine ingestion does not impair glucose tolerance in persons with tetraplegia J Appl Physiol, January 1, 2007; 102(1): 374 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A Greenberg, C. N Boozer, and A. Geliebter Coffee, diabetes, and weight control. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 682 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lopez-Garcia, R. M. van Dam, W. C. Willett, E. B. Rimm, J. E. Manson, M. J. Stampfer, K. M. Rexrode, and F. B. Hu Coffee Consumption and Coronary Heart Disease in Men and Women: A Prospective Cohort Study Circulation, May 2, 2006; 113(17): 2045 - 2053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Battram, R. Arthur, A. Weekes, and T. E. Graham The Glucose Intolerance Induced by Caffeinated Coffee Ingestion Is Less Pronounced than That Due to Alkaloid Caffeine in Men J. Nutr., May 1, 2006; 136(5): 1276 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Lopez-Garcia, R. M van Dam, S. Rajpathak, W. C Willett, J. E Manson, and F. B Hu Changes in caffeine intake and long-term weight change in men and women Am. J. Clinical Nutrition, March 1, 2006; 83(3): 674 - 680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. B. Norager, M. B. Jensen, M. R. Madsen, and S. Laurberg Caffeine improves endurance in 75-yr-old citizens: a randomized, double-blind, placebo-controlled, crossover study J Appl Physiol, December 1, 2005; 99(6): 2302 - 2306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Battram, T. E. Graham, E. A. Richter, and F. Dela The effect of caffeine on glucose kinetics in humans - influence of adrenaline J. Physiol., November 15, 2005; 569(1): 347 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. van Dam and F. B. Hu Coffee Consumption and Risk of Type 2 Diabetes: A Systematic Review JAMA, July 6, 2005; 294(1): 97 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lee, R. Hudson, K. Kilpatrick, T. E. Graham, and R. Ross Caffeine Ingestion Is Associated With Reductions in Glucose Uptake Independent of Obesity and Type 2 Diabetes Before and After Exercise Training Diabetes Care, March 1, 2005; 28(3): 566 - 572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. E. Robinson, S. Savani, D. S. Battram, D. H. McLaren, P. Sathasivam, and T. E. Graham Caffeine Ingestion Before an Oral Glucose Tolerance Test Impairs Blood Glucose Management in Men with Type 2 Diabetes J. Nutr., October 1, 2004; 134(10): 2528 - 2533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J Petrie, S. E Chown, L. M Belfie, A. M Duncan, D. H McLaren, J. A Conquer, and T. E Graham Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss Am. J. Clinical Nutrition, July 1, 2004; 80(1): 22 - 28. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Salazar-Martinez, W. C. Willett, A. Ascherio, J. E. Manson, M. F. Leitzmann, M. J. Stampfer, and F. B. Hu Coffee Consumption and Risk for Type 2 Diabetes Mellitus Ann Intern Med, January 6, 2004; 140(1): 1 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hosoda, M.-F. Wang, M.-L. Liao, C.-K. Chuang, M. Iha, B. Clevidence, and S. Yamamoto Antihyperglycemic Effect of Oolong Tea in Type 2 Diabetes Diabetes Care, June 1, 2003; 26(6): 1714 - 1718. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
], caffeine at 5 mg/kg (CAF,
), 80 mg of propranolol (PR, 
), and
CAF + PR (
). Values are means ± SE
(n = 7). Blood glucose increased (P < 0.05) similarly in all 4 trials in response to a 75-g glucose load at
15 min and throughout the OGTT.
P < 0.05 vs. PL, CAF, and
CAF + PR.
