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Contribution of protein kinase Cα in the stimulation of insulin by the down-regulation of Cavβ subunits

Abstract

Voltage-gated calcium (Cav) channels and protein kinase C (PKC) isozymes are involved in insulin secretion. In addition, Cavβ, one of the auxiliary subunits of Cav channels, also regulates the secretion of insulin as knockout of Cavβ3 (β3−/−) subunits in mice led to efficient glucose homeostasis and increased insulin levels. We examined whether other types of Cavβ subunits also have similar properties. In this regard, we used small interfering RNA (siRNA) of these subunits (20 μg each) to down-regulate them and examined blood glucose, serum insulin and PKC translocation in isolated pancreatic β cells of mice. While the down-regulation of Cavβ2 and β3 subunits increased serum insulin levels and caused efficient glucose homeostasis, the down-regulation of Cavβ1 and β4 subunits failed to affect both these parameters. Examination of PKC isozymes in the pancreatic β-cells of Cavβ2- or β3 siRNA-injected mice showed that three PKC isozymes, viz., PKC α, βII and θ, translocated to the membrane. This suggests that when present, Cavβ2 and β3 subunits inhibited PKC activation. Among these three isozymes, only PKCα siRNA inhibited insulin and increased glucose concentrations. It is possible that the activation of PKCs βII and θ is not sufficient for the release of insulin and PKCα is the mediator of insulin secretion under the control of Cavβ subunits. Since Cavβ subunits are present intracellularly, it is possible that they (1) inhibited the translocation of PKC isozymes to the membrane and (2) decreased the interaction between Cav channels and PKC isozymes and thus the secretion of insulin.

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Acknowledgments

This work was supported by National Institutes of General Medical Sciences (SCORE3, GM096947) to G.L.K. The project described was supported in part by Grant Number G11HD052382 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the views of the National Institute of Child Health and Human Development or the National Institutes of Health.

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The authors fully declare any financial or other potential conflict of interest.

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Correspondence to Ganesan L. Kamatchi.

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Rajagopal, S., Fields, B.L. & Kamatchi, G.L. Contribution of protein kinase Cα in the stimulation of insulin by the down-regulation of Cavβ subunits. Endocrine 47, 463–471 (2014). https://doi.org/10.1007/s12020-013-0149-y

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Keywords

  • Cavβ subunits
  • PKCα
  • Insulin
  • Calcium channels