title: Akt signals upstream of L-type calcium channels to optimize insulin secretion.
abstract: OBJECTIVE
  Both the serine/threonine protein kinase Akt and the voltage-gated L-type calcium channel act as important players in glucose-stimulated insulin secretion. Akt recruits the L-type calcium channel to and maintains them in the plasma membrane. This study aimed to characterize the role of L-type calcium channels in mediation of Akt signaling in glucose-stimulated insulin secretion.
  
  
  METHODS
  Insulin secretion was evaluated in rat pancreatic islets and INS-1 pancreatic β cells by a standard insulin radioimmunoassay.
  
  
  RESULTS
  Akt inhibition effectively abrogates not only glucose-stimulated but also potassium depolarization-stimulated insulin secretion from rat islets, the latter critically relying on the voltage-gated calcium channel-mediated Ca(2+) influx without involvement of glucose metabolism. Likewise, Akt inhibition also reduces both glucose-stimulated and potassium depolarization-stimulated insulin secretion from INS-1 cells. Importantly, pharmacological ablation of L-type calcium channels partially blocks Akt inhibition-induced reduction in glucose-stimulated insulin secretion but completely prevents that in potassium depolarization-evoked insulin release from INS-1 cells. Furthermore, Akt inhibition does not influence calcium ionophore A23187-induced insulin secretion from INS-1 cells, which occurred without involvement of L-type calcium channels.
  
  
  CONCLUSIONS
  Akt signals upstream of L-type calcium channels to optimize glucose-stimulated insulin secretion.
authors.affiliation: Endocrinology and Metabolic Diseases Laboratory, Tianjin Medical University, Tianjin, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Cui
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Minglin
authors.initials: M
authors.lastname: Pan
authors.forename: Xiao-Nan
authors.initials: XN
authors.lastname: Zhang
authors.forename: Shao-Nian
authors.initials: SN
authors.lastname: Yang
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D061207:Calcium Ionophores / Q000494:pharmacology; D045744:Cell Line, Tumor; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D061207:Calcium Ionophores; D007328:Insulin; D021122:Protein Subunits; D000001:Calcimycin; D011189:Potassium Chloride; D051057:Proto-Oncogene Proteins c-akt; D009543:Nifedipine; D005947:Glucose; D002118:Calcium