Effects of cholinergic m-receptor agonists on insulin release in islets from obese and lean mice of different ages: the importance of bicarbonate

Pancreas. 2004 Nov;29(4):e90-9. doi: 10.1097/00006676-200411000-00162.


Objectives: Decreased beta-cell function is often observed in older individuals and may predispose to the development of type 2 diabetes. We have studied the age-related effects of M-receptor agonism on insulin release in islets isolated from female ob/ ob and lean mice.

Methods: Islets were challenged with 11.1 or 16.7 mmol/L glucose in media with HCO3/CO2 (KRBH) or without (KRH).

Results: Acetylcholine (ACh) (10 micromol/L) increased glucose-induced insulin release in islets from 4- to 5-week-old ob/ob mice both in KRBH and KRH. In islets from 9- to 13-month-old ob/ob mice, 10 micromol/L ACh and 10 micromol/L carbachol enhanced insulin release in KRBH but not in KRH. ACh increased insulin release in islets from 4- to 5-week-old and 16-month-old lean mice incubated in KRH but not in islets from 24-month-old lean mice. The Na/H exchange inhibitor dimethylamiloride (100 micromol/L) did not affect insulin release stimulated by M-receptor agonists. Carbachol did not enhance glucose-induced insulin secretion in islets from 9- to 10-month-old ob/ob mice in the presence of low extracellular Na concentration. ACh stimulated cytoplasmic Ca mobilization in islets from 9- to 10-month-old mice also when bicarbonate was omitted. The results suggest that cholinergic signal transduction involving extracellular bicarbonate and Na is reduced with age in mouse pancreatic islets.

Conclusion: Chronic hyperglycemia may add to the age-related decrease in M-receptor-mediated insulin release by affecting the buffering capacity of the islets through mechanisms other than amiloride-sensitive proton exchange.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / pharmacology
  • Acetylcholine / pharmacology
  • Age Factors
  • Amiloride / pharmacology
  • Ammonium Chloride / pharmacology
  • Animals
  • Bicarbonates / metabolism*
  • Calcium / metabolism
  • Carbachol / pharmacology
  • Chlorides / metabolism
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • Female
  • Glucose / metabolism
  • In Vitro Techniques
  • Insulin / metabolism*
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / cytology
  • Islets of Langerhans / drug effects*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Obese
  • Muscarinic Agonists / pharmacology*
  • Obesity / metabolism*
  • Oxidation-Reduction
  • Sodium / metabolism
  • Thinness / metabolism*


  • Bicarbonates
  • Chlorides
  • Insulin
  • Muscarinic Agonists
  • Ammonium Chloride
  • Amiloride
  • Carbachol
  • Sodium
  • Glucose
  • Acetylcholine
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid
  • Calcium