Effects of high-dose troglitaz one on insulin sensitivity and beta-cell function in Watanabe heritable hyperlipidemic rabbits.
To clarify the dose-response effects of troglitazone on insulin sensitivity and beta-cell function, we examined the effects of high-dose troglitazone (100 mg/day per animal, administered as a food admixture) on glucose and insulin metabolism in hyperinsulinemic Watanabe heritable hyperlipidemic (WHHL) rabbits, and compared the results with our previous results with low-dose troglitazone (10 mg /day per animal).


METHODS
Glucose and insulin metabolism were quantitatively characterized by a minimal model technique as reported previously.


RESULTS
When troglitazone was administrated at a high dose for 6 months, it reduced hyperinsulinemia as reflected by a reduced basal (steady-state) insulin concentration lb and the insulin response to a glucose load, improved beta-cell function as reflected by decreased second-phase post-hepatic insulin delivery to glucose phi2, and reduced insulin resistance as reflected by increased insulin sensitivity to glucose disposal Si, without affecting glucose tolerance as reflected by an unchanged rate of glucose utilization Kg or insulin-independent glucose disposal Sg. The reductions in Ib and phi2 and the increases in Si in WHHL rabbits treated with a high dose of troglitazone were greater (p<0.05) than those observed in WHHL rabbits treated with a low dose of troglitazone, as assessed by a two-way repeated measures analysis of variance and the Wilcoxon-Mann-Whitney test.


CONCLUSIONS
In WHHL rabbits, troglitazone dose-dependently reduced hyperinsulinemia, improved beta-cell function, and increased insulin sensitivity.
Zhang
B
B
Department of Internal Medicine, Fukuoka University, Japan.
Shiomi
M
M
Tanaka
H
H
Mei
J
J
Fan
P
P
Tsujita
Y
Y
Horikoshi
H
H
Saku
K
K
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005951:Glucose Tolerance Test; D006949:Hyperlipidemias / Q000235:genetics* / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000187:drug effects*; D008954:Models, Biological; D011817:Rabbits; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; D045162:Thiazolidinediones; D000077288:Troglitazone