A highly energetic process couples calcium influx through L-type calcium channels to insulin secretion in pancreatic -cells
نویسندگان
چکیده
Jung SR, Reed BJ, Sweet IR. A highly energetic process couples calcium influx through L-type calcium channels to insulin secretion in pancreatic -cells. Am J Physiol Endocrinol Metab 297: E717–E727, 2009. First published July 7, 2009; doi:10.1152/ajpendo.00282.2009.— Calcium (Ca ) influx is required for the sustained secretion of insulin and is accompanied by a large rate of energy usage. We hypothesize that the energy usage reflects a process [Ca /metabolic coupling process (CMCP)] that couples Ca to insulin secretion by pancreatic islets. The aim of the study was to test this hypothesis by testing the effect of inhibiting candidate Ca -sensitive proteins proposed to play a critical role in the CMCP. The effects of the inhibitors on oxygen consumption rate (OCR), a reflection of ATP usage, and insulin secretion rate (ISR) were compared with those seen when L-type Ca channels were blocked with nimodipine. We reasoned that if a downstream Ca -regulated site was responsible for the OCR associated with the CMCP, then its inhibition should mimic the effect of nimodipine. Consistent with previous findings, nimodipine decreased glucose-stimulated OCR by 36% and cytosolic Ca by 46% and completely suppressed ISR in rat pancreatic islets. Inhibitors of three calmodulin-sensitive proteins (myosin light-chain kinase, calcineurin, and Ca /calmodulin-dependent protein kinase II) did not meet the criteria. In contrast, KN-62 severed the connection between Ca influx, OCR, and ISR without interfering with Ca influx. In the presence of nimodipine or KN-62, potentiators of ISR, acetylcholine, GLP-1, and arginine had little effect on insulin secretion, suggesting that the CMCP is also essential for the amplification of ISR. In conclusion, a KN-62-sensitive process directly mediates the effects of Ca influx via L-type Ca channels on OCR and ISR, supporting the essential role of the CMCP in mediating ISR.
منابع مشابه
A highly energetic process couples calcium influx through L-type calcium channels to insulin secretion in pancreatic beta-cells.
Calcium (Ca(2+)) influx is required for the sustained secretion of insulin and is accompanied by a large rate of energy usage. We hypothesize that the energy usage reflects a process [Ca(2+)/metabolic coupling process (CMCP)] that couples Ca(2+) to insulin secretion by pancreatic islets. The aim of the study was to test this hypothesis by testing the effect of inhibiting candidate Ca(2+)-sensit...
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