Involvement of the cholinergic pathway in glucocorticoid-induced hyperinsulinemia in rats.
OBJECTIVE
We investigated the contribution of the cholinergic nervous system to dexamethasone-induced insulin resistance and hyperinsulinemia in rats.


METHODS
Seventy-day-old Wistar male rats were distributed in groups: control (CTL), vagotomized (VAG), and sham operated (SHAM). On the 90th day of life, half of the rats were treated daily with 1mg/kg of dexamethasone for 5 days (CTL DEX, VAG DEX, and SHAM DEX).


RESULTS
In the presence of 8.3mM glucose plus 100microM carbachol (Cch), isolated islets from CTL DEX secreted significantly more insulin than CTL. Cch-enhancement of secretion was further increased in islets from VAG CTL and VAG DEX than SHAM CTL and SHAM DEX, respectively. In CTL DEX islets, M3R and PLCbeta1 and phosphorylated PKCalpha, but not PKCalpha, protein content was significantly higher compared with each respective control. In islets from VAG DEX, the expression of M3R protein increased significantly compared to VAG CTL and SHAM DEX. Vagotomy per se did not affect insulin resistance, but attenuated fasted and fed insulinemia in VAG DEX, compared with SHAM DEX rats.


CONCLUSIONS
These data indicate an important participation of the cholinergic nervous system through muscaric receptors in dexamethasone-induced hyperinsulinemia in rats.
Angelini
Nágela
N
Department of Anatomy, Cellular Biology and Physiology, Institute of Biology, State University of Campinas, São Paulo, Brazil.
Rafacho
Alex
A
Boschero
Antonio Carlos
AC
Bosqueiro
José Roberto
JR
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004361:Drug Tolerance; D005938:Glucocorticoids / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects / Q000502:physiology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D011994:Recombinant Proteins; D003907:Dexamethasone; D002217:Carbachol; D005947:Glucose