In vivo and in vitro suppression by leptin of glucose-stimulated insulin hypersecretion in high glucose-fed rats.
OBJECTIVE
Chronic feeding to rats of high glycaemic index (GI) diets results in the hypersecretion of insulin in response to an i.v. glucose load. The first aim of this study was to see if this exaggerated insulin response was accompanied by a hypersensitivity to glucose stimulation in isolated islets in vitro. The second aim was to see if the adipocyte factor, leptin, was able to alter insulin secretion in this model both in vivo and in vitro.


METHODS
Rats were fed for 6 weeks either a high GI diet in which the carbohydrate component was mostly glucose (GLUC diet) or a low GI diet containing mostly amylose (AMOSE diet). Rats then underwent an i.v. glucose tolerance test (ivGTT) (1g/kg) with and without a prior infusion of leptin (133 microg/kg perh). Islets were then isolated from these rats and basal and glucose-stimulated insulin secretion (GSIS) measured in both the absence and presence (100ng/ml) of leptin.


CONCLUSIONS
Peak insulin response during the ivGTT was 3-fold greater in GLUC rats (P<0.001). Leptin had no effect on AMOSE rat insulin response but lowered the GLUC rat response to AMOSE rat levels. In vitro, basal insulin secretion was 4-fold greater in GLUC rats (P<0.05). At 20mmol/l glucose, there was no further increase in insulin secretion in GLUC rats but a 2-fold increase in AMOSE rats. Leptin had no effect on basal insulin secretion or GSIS in AMOSE rats but reduced basal insulin secretion and GSIS in GLUC rats. These results show insulin hypersecretion in high GI-fed rats may be reduced by leptin.
Widdup
G
G
Human Nutrition Unit, Department of Biochemistry, University of Sydney, Sydney, New South Wales 2006, Australia.
Bryson
J M
JM
Pawlak
D
D
Phuyal
J L
JL
Denyer
G S
GS
Caterson
I D
ID
D000818:Animals; D019540:Area Under Curve; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D005947:Glucose / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D020738:Leptin; D005947:Glucose