Effect of insulin on acetylcholine-evoked amylase release and calcium mobilization in streptozotocin-induced diabetic rat pancreatic acinar cells.
This article investigated the effect of acetylcholine (ACh) on amylase secretion and cellular calcium homeostasis [Ca2+]i in streptozotocin (STZ; 60 mg kg(-1), intraperitoneally)-induced diabetic rats compared to age-matched controls in an attempt to understand the cellular mechanism of exocrine pancreatic insufficiency. ACh-evoked marked dose-dependent increases in amylase release from isolated pancreatic acini and acinar cells in healthy control rats. In diabetic acini and acinar cells, the ACh-evoked amylase release was significantly (P < 0.05) reduced compared to healthy acini and acinar cells. Insulin (10(-6)M) stimulated amylase release in both control and diabetic acini and acinar cells but with a much reduced effect in diabetic tissues. Combining insulin with ACh had no significant effect on amylase release compared to the effect of ACh alone. In fura-2 loaded pancreatic acinar cells of normal rats, ACh (10(-5)M) evoked a large initial rise (peak) in [Ca2+]i followed by a decline into a plateau phase. This effect of ACh was significantly (P < 0.05) reduced in fura-2 loaded diabetic acinar cells. In control cells, insulin had no significant effect on either basal or ACh evoked [Ca2+]i compared to the effect of ACh alone. In contrast, in diabetic acinar cells, insulin significantly (P < 0.05) attenuated the effect of ACh. In a normally free extracellular Ca2+ medium [Ca2+]o containing 1 mM EGTA, the ACh-evoked [Ca2+]i in normal healthy fura-2 loaded acini was similar to the response obtained with ACh in fura-2 loaded diabetic acini. Together, the results indicated that exocrine pancreatic insufficiency is associated with decreased [Ca2+]i due to less Ca2+ released from internal stores and less Ca2+ entering the cell from the extracellular medium.
Patel
Rekha
R
Department of Biological Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE UK.
Pariente
José A
JA
Martinez
Maria A
MA
Salido
Ginés M
GM
Singh
Jaipaul
J
D000109:Acetylcholine / Q000494:pharmacology*; D000681:Amylases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009929:Organ Size; D010179:Pancreas / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D007328:Insulin; D000681:Amylases; D000109:Acetylcholine