Crocetin Prevents Dexamethasone-Induced Insulin Resistance in Rats

Abstract

The main objective of the study was to examine whether crocetin, a natural product from Gardenia jaminoides Ellis, has beneficial effects on the state of insulin resistance induced by dexamethasone in a rat model. Measured using the oral glucose tolerance tests (OGTT), male Wistar rats treated with subcutaneous dexamethasone (0.08 mg/kg/d) for 6 weeks exhibited reduced insulin sensitivity at weeks 2 and 4 and impaired glucose tolerance at week 4. In the dexamethasone-treated group, serum insulin, free fatty acids (FFA), triglyceride (TG) and tumor necrosis factor (TNF)-α levels were significantly increased at the end of the study. In addition, the hepatic glycogen content was reduced as indicated by periodic acid-Schiff (PAS) staining, and pancreatic islet β cells showed compensatory hyperactivity suggested by immunohistochemical (IHC) staining using an antibody against insulin. Treatment with crocetin (40 mg/kg/d) significantly attenuated all the described effects of dexamethasone. These results suggest that crocetin might prevent the development of dexamethasone-induced insulin resistance and related abnormalities in rats.

Abbreviations

AUC:area under the curve

CON:control

CRO(H):high-dose crocetin

CRO(L):low-dose crocetin

CRO:crocetin

DEX:dexamethasone

FFA:free fatty acids

GAUC:area under the glucose curve

HE:hematoxylin-eosin

IAUC:area under the insulin curve

IHC:immunohistochemical

ISI:insulin sensitivity index

MET:metformin

OGTT:oral glucose tolerance test

PAS:periodic acid-Schiff

TG:triglyceride

TNF:tumor necrosis factor

Key words

Crocetin - glucocorticoids - insulin resistance - impaired glucose tolerance - rats

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