Effects of muscarinic receptor type 3 knockout on mouse islet secretory responses

• Published in: Biochemical and biophysical research communications Vol. 315; no. 4; pp. 872 - 876
• Main Authors: Zawalich, Walter S, Zawalich, Kathleen C, Tesz, Gregory J, Taketo, Makoto M, Sterpka, John, Philbrick, William, Matsui, Minoru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.03.2004
• Subjects: Animals; Carbachol - metabolism; Carbachol - pharmacology; Cholinergic; Enzyme Activation - drug effects; Female; Glucose - metabolism; Glucose - pharmacology; Heterozygote; Inositol - analogs & derivatives; Inositol - metabolism; Insulin; Insulin - blood; Insulin - metabolism; Insulin Secretion; Islets; Islets of Langerhans - metabolism; Islets of Langerhans - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptor, Muscarinic M3 - deficiency; Receptor, Muscarinic M3 - genetics; Secretion; Type C Phospholipases - metabolism; Islets; Secretion; Insulin; Cholinergic
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2004.01.139

The impact of muscarinic type 3 receptor knockout (M 3KO) on the cholinergic regulation of insulin secretion and phospholipase C (PLC) activation was determined. Islets isolated from control, wild-type mice or heterozygotes responded with comparable insulin secretory responses to 15 mM glucose. This response was markedly amplified by the inclusion of 10 μM carbachol. While 15 mM glucose-induced release remained similar to wild-type and heterozygote responses in M 3KO mice, the stimulatory impact of carbachol was abolished. Stimulation with 15 mM glucose plus 50 μM carbachol increased fractional efflux rates of myo-[2- 3H]inositol from control wild-type and heterozygote islets but not from M 3KO islets. Fed plasma insulin levels of M 3KO mice were reduced 68% when compared to values obtained from combined wild-type and heterozygote animals. These studies support the conclusion that the M 3 receptor in islets is coupled to PLC activation and insulin secretion and that cholinergic stimulation of the islets may play an important role in the regulation of plasma insulin levels.