Glucokinase activation induces potent hypoglycemia without recruiting insulin and inhibits food intake in chicken.
Glucose homeostasis exhibits several peculiarities in chickens (in short, presence of high glycemia and resistance to high doses of exogenous insulin). Though the full chicken glucokinase gene sequence is still lacking, several results suggest its existence. The functionality of chicken glucokinase (GK) has been further investigated using an activator of mammalian GK (GKA). In vitro, GKA decreased GK's S0.5(a) in a glucose-dependent manner in liver homogenates from either fasted or fed chickens; it also increased GK Vmax(a) in homogenates from fed chickens. In vivo, acute oral GKA administration (10-100 mg/kg) induced a potent and dose dependent hypoglycemic effect in fed chickens (starting between 15 and 45 min with a maximum effect at 40 mg/kg, P<0.0001). At this dose, plasma insulin levels showed erratic and minor changes in the early times (an increase at 5 min and a decrease at 10 min, P<0.05). At 90 min, when hypoglycemia had developed plasma insulin levels decreased under controls and plasma pancreatic glucagon levels increased over controls. Also at 40 mg/kg, GKA transiently inhibited food intake at about 3h (P<0.0001). In conclusion, GKA is a potent activator of chicken GK evidencing that the structure and the activity of chicken GK are similar to those of mammalian GK. At variance with results obtained in mammals, the potent GKA hypoglycemic action appears to rely mostly on an effect on liver GK in chicken. This fits with previous results and further support the hypothesis of a "deficient coupling" between Β-cell metabolism and insulin release in this species.
Rideau
Nicole
N
INRA, UR83 Recherches Avicoles, 37380 Nouzilly, France. Nicole.Rideau@tours.inra.fr
Derouet
Michel
M
Grimsby
Joseph
J
Simon
Jean
J
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002645:Chickens; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation; D005215:Fasting; D005934:Glucagon / Q000097:blood; D005941:Glucokinase / Q000378:metabolism*; D007003:Hypoglycemia / Q000139:chemically induced*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D008297:Male; D013450:Sulfones / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*
C549923:3-cyclopentyl-2-(4-methanesulfonylphenyl)-N-thiazol-2-yl-propionamide; D001786:Blood Glucose; D007328:Insulin; D013450:Sulfones; D013844:Thiazoles; D005934:Glucagon; D005941:Glucokinase