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

Biochem Biophys Res Commun. 2004 Mar 19;315(4):872-6. doi: 10.1016/j.bbrc.2004.01.139.


The impact of muscarinic type 3 receptor knockout (M3KO) 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 microM carbachol. While 15 mM glucose-induced release remained similar to wild-type and heterozygote responses in M3KO mice, the stimulatory impact of carbachol was abolished. Stimulation with 15 mM glucose plus 50 microM carbachol increased fractional efflux rates of myo-[2-3H]inositol from control wild-type and heterozygote islets but not from M3KO islets. Fed plasma insulin levels of M3KO mice were reduced 68% when compared to values obtained from combined wild-type and heterozygote animals. These studies support the conclusion that the M3 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbachol / metabolism
  • Carbachol / pharmacology
  • Enzyme Activation / drug effects
  • Female
  • Glucose / metabolism
  • Glucose / pharmacology
  • Heterozygote
  • Inositol / analogs & derivatives
  • Inositol / metabolism
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptor, Muscarinic M3 / deficiency*
  • Receptor, Muscarinic M3 / genetics
  • Type C Phospholipases / metabolism


  • Insulin
  • Receptor, Muscarinic M3
  • Inositol
  • Carbachol
  • Type C Phospholipases
  • Glucose