Effects of exenatide on circulating glucose, insulin, glucagon, cortisol and catecholamines in healthy volunteers during exercise.
OBJECTIVE
Exenatide, a glucagon like peptide-1 agonist, is a treatment for type 2 diabetes mellitus that stimulates insulin and suppresses glucagon secretion in a glucose-dependent manner. By contrast, during aerobic exercise, the serum insulin concentration normally falls, with a rise in plasma glucagon. We therefore assessed whether exenatide might predispose to hypoglycaemia during exercise.


METHODS
We studied eight non-diabetic men, who were 35.3 +/- 6.3 years of age with BMI of 24.7 +/- 1.7 kg/m(2) (mean +/- SD), using a randomised, crossover, double-blind design investigation. After an overnight fast, participants received 5 microg of subcutaneous exenatide or placebo and rested for 105 min before cycling at 60% of their maximal oxygen uptake (VO(2max)) for 75 min and then recovering for a further 60 min.


RESULTS
The insulin/glucagon molar ratio rose with exenatide at rest (p < 0.01), then fell during exercise with placebo and with exenatide. At rest, fasting blood glucose fell by approximately 1 mmol/l with exenatide to a nadir of 3.4 +/- 0.1 mmol/l (p < 0.01). During exercise, blood glucose fell with placebo but, unexpectedly, rose with exenatide. Plasma adrenaline (epinephrine) and noradrenaline (norepinephrine), but not cortisol concentrations increased to a greater extent during exercise after exenatide. No participant developed symptomatic hypoglycaemia and the lowest individual blood glucose recorded was 2.8 mmol/l with exenatide at 50 min in the pre-exercise period.


CONCLUSIONS
In non-diabetic participants given exenatide, blood glucose concentrations rise rather than fall during aerobic exercise with an associated greater catecholamine response.
Khoo
E Y H
EY
Department of Diabetes and Endocrinology, Nottingham University Hospitals, Queens Medical Centre Campus, Nottingham NG7 2UH, UK.
Wallis
J
J
Tsintzas
K
K
Macdonald
I A
IA
Mansell
P
P
D000328:Adult; D001642:Bicycling / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D000077270:Exenatide; D015444:Exercise / Q000502:physiology*; D005934:Glucagon / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood*; D007773:Lactates / Q000097:blood; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010455:Peptides / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D014688:Venoms / Q000097:blood / Q000494:pharmacology*
D001786:Blood Glucose; D002395:Catecholamines; D007004:Hypoglycemic Agents; D007328:Insulin; D007773:Lactates; D010455:Peptides; D014688:Venoms; D005934:Glucagon; D000077270:Exenatide; D006854:Hydrocortisone