Effects of cholinergic m-receptor agonists on insulin release in islets from obese and lean mice of different ages: the importance of bicarbonate.
2004 (English)In: Pancreas, ISSN 1536-4828, Vol. 29, no 4, e90-9 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2004. Vol. 29, no 4, e90-9 p.
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/metabolism, Female, Glucose/metabolism, Insulin/*metabolism, Islets of Langerhans/chemistry/cytology/*drug effects, Mice, Mice; Inbred BALB C, Mice; Obese, Muscarinic Agonists/*pharmacology, Obesity/*metabolism, Oxidation-Reduction, Sodium/metabolism, Thinness/*metabolism
IdentifiersURN: urn:nbn:se:umu:diva-12236PubMedID: 15502638OAI: oai:DiVA.org:umu-12236DiVA: diva2:151907