Role for calcium in the insulin hypersecretory state of the endotoxic rat pancreas.
Previous studies have demonstrated that the endotoxic rat pancreas hypersecretes insulin in response to a glucose stimulus. However, the mechanism for this phenomenon is unknown. Since increases in pancreatic beta (B)-cell cytosolic ionic calcium are required for insulin secretion, this study evaluated the role of extracellular calcium on insulin secretion from the isolated, perfused endotoxic pancreas in the presence of and in the absence of extracellular calcium. Isolated pancreas preparations were obtained from control and endotoxin-treated rats and were perfused with either glucose (which primarily utilizes extracellular calcium to trigger insulin secretion) or 3-isobutyl-1-methylxanthine (IBMX, which primarily utilizes intracellular calcium to trigger secretion). In the presence of extracellular calcium, endotoxic pancreases hypersecreted insulin in response to either glucose or IBMX in comparison to control pancreases. In the absence of extracellular calcium, no insulin secretion occurred from control pancreases perfused with either glucose or IBMX. For endotoxic pancreases perfused with calcium-free conditions, insulin secretion was substantially less than that which occurred in the presence of calcium, but a significant amount of insulin secretion occurred from endotoxic pancreases in response to either IBMX or glucose. Insulin secretion from endotoxic pancreases was nearly three times greater with IBMX than with glucose under calcium-free conditions. Owing to the manner in which IBMX triggers insulin release, these data suggest that calcium handling within the endotoxic B-cell differs from that of the normal B-cell. In addition, endotoxic hypersecretion of insulin did not occur in response to endotoxin in vitro. Therefore this study indicates that endotoxin alters the regulation of calcium movements within the pancreatic B-cell via a mediated pathway.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology*; D004731:Endotoxins / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006946:Hyperinsulinism / Q000209:etiology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012477:Salmonella enteritidis; D012772:Shock, Septic / Q000503:physiopathology*
D004731:Endotoxins; D007328:Insulin; D005947:Glucose; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine