Muscarinic M2 receptor is active on pancreatic islets from hypothalamic obese rat.
Hypothalamic obese rats, obtained by neonatal treatment with monosodium L-glutamate (MSG), are hyperinsulinemic, and secrete more insulin than lean ones do when stimulated by glucose, while acetylcholine insulinotropic effect decreases. The effect of acetylcholine on glucose-induced insulin secretion is attributed to muscarinic receptors of pancreatic beta cells, mainly to M(3) subtype. However, it has been observed that activation of M(2) or M(4) subtypes causes inhibition of glucose-induced insulin secretion in insulin secreting cell line. Insulin secretion was measured, stimulated by glucose in the presence of acetylcholine plus methoctramine, a muscarinic M(2) antagonist, on pancreatic islets isolated from MSG-obese and lean rats to investigate whether impairment of acetylcholine insulinotropic effect on pancreatic islets from MSG-obese rats has any relationship with muscarinic M(2) receptor function in beta cells. Insulin secretion stimulated by 8.3 mM glucose was higher in islets from obese rats than from lean ones. Insulinotropic effect of acetylcholine was reported in islets of both animals, albeit less than in obese ones. Blockage of muscarinic M(2) receptor, using methoctramine at 1; 5 and 10 microM, increased acetylcholine secretory response in islets of obese rats, while no effect has been observed in lean ones. Results demonstrate that muscarinic M(2) receptors are functioning in pancreatic islets of MSG-obese rats. The inhibitory action of muscarinic M(2) receptor may be a mechanism by which acetylcholine discloses weak insulinotropic effect in MSG-obese rats.
Grassiolli
Sabrina
S
Laboratory of Secretion Cell Biology, Department of Cell Biology and Genetics, State University of Maringá, Avenida Colombo 5790, 87020-900 Maringá, Brazil.
Gravena
Clarice
C
de Freitas Mathias
Paulo Cezar
PC
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003959:Diamines / Q000494:pharmacology; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000503:physiopathology*; D066298:In Vitro Techniques; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology*; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009765:Obesity / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012970:Sodium Glutamate
D003959:Diamines; D043585:Receptor, Muscarinic M2; D009388:Neostigmine; D000109:Acetylcholine; C054938:methoctramine; D012970:Sodium Glutamate