Functional alterations in endocrine pancreas of rats with different degrees of dexamethasone-induced insulin resistance.
OBJECTIVE
We have analyzed the peripheral insulin and glucose sensitivity in vivo, and islet function ex vivo in rats with different degrees of insulin resistance induced by dexamethasone (DEX).


METHODS
Dexamethasone, in the concentrations of 0.1 (DEX 0.1), 0.5 (DEX 0.5), and 1.0 mg/kg body weight (DEX 1.0) was administered daily, intraperitoneally, to adult Wistar rats for 5 days, whereas controls received saline.


RESULTS
Dexamethasone treatment induced peripheral insulin resistance in a dose-dependent manner. At the end of the treatment, only DEX 1.0 rats showed significant increase of postabsorptive blood glucose and serum triglycerides, and nonesterified fatty acids levels. Incubation of pancreatic islets in increasing glucose concentrations (2.8-22 mM) led to an augmented insulin secretion in all DEX-treated rats. Leucine, carbachol, and high KCl concentrations induced the insulin release in DEX 0.5 and DEX 1.0, whereas arginine augmented secretion in all DEX-treated groups.


CONCLUSIONS
We demonstrate that in DEX 0.5 and, especially in DEX 0.1 groups, but not in DEX 1.0, the adaptations that occurred in the endocrine pancreas are able to counteract metabolic disorders (glucose intolerance and dyslipidemia). These animal models seem to be interesting approaches for the study of degrees of subjacent effects that may mediate type 2 diabetes (DEX 1.0) and islet function alterations, without collateral effects (DEX 0.1 and DEX 0.5).
Rafacho
Alex
A
Department of Physiology and Biophysics, Institute of Biology, State University of Campinas, Campinas, Brazil.
Giozzet
Vanessa A G
VA
Boschero
Antonio C
AC
Bosqueiro
José R
JR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000633:toxicity*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005938:Glucocorticoids / Q000008:administration & dosage / Q000633:toxicity*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D007328:Insulin; D014280:Triglycerides; D003907:Dexamethasone; D005947:Glucose