cAMP-independent decrease of ATP-sensitive K+ channel activity by GLP-1 in rat pancreatic β-cells (original) (raw)

Abstract.

Using the patch-clamp method, we studied the mechanism of depolarization of rat pancreatic β-cells induced by glucagon-like peptide 1 (7–36) amide (GLP-1). GLP-1 caused depolarization in a concentration-dependent manner (0.2–100 nM). Exendin (9–39) amide, a GLP-1 receptor antagonist, prevented the GLP-1-induced depolarization. GLP-1 reduced tolbutamide-sensitive membrane currents evoked by voltage ramps from –90 to –50 mV, recorded in the perforated whole-cell configuration, suggesting that GLP-1 decreased the activity of the ATP-sensitive K+ channel (KATP). This GLP-1 effect was prevented by exendin (9–39) amide. In cells treated with Rp-cAMPS, an inhibitor of the cAMP-dependent protein kinase (PKA), GLP-1 still caused depolarization and reduced the whole-cell membrane current through KATP. Examined in the cell-attached configuration, 20 nM GLP-1, applied out of the patch, had little effect on KATP activity. In the inside-out configuration, the open time probability and the single-channel conductance of KATP in the absence of ATP inside the membrane were unaffected by the presence of 20 nM GLP-1 in the pipette. In both conditions, application of ATP to the inside of the membrane reduced KATP activity. The half-maximal concentrations (k i) of ATP were 11.6 µM without and 5.6 µM with 20 nM GLP-1 in the pipette (P<0.05). The values of the Hill coefficient (h) were 1.03 without and 1.01 with GLP-1. We conclude that GLP-1 reduces KATP activity by elevating the sensitivity of KATP to ATP, resulting in depolarization of pancreatic β-cells. This GLP-1 action is independent of the cAMP signalling pathway.

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Authors and Affiliations

  1. Department of Physiology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036–8562, Japan, , , , ,
    Sechiko Suga, Takahiro Kanno, Teruko Takeo, Noritaka Kamimura & Makoto Wakui
  2. The Third Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki 036–8562, Japan, , , , ,
    Yoshiji Ogawa

Authors

  1. Sechiko Suga
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  2. Takahiro Kanno
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  3. Yoshiji Ogawa
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  4. Teruko Takeo
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  5. Noritaka Kamimura
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  6. Makoto Wakui
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Received after revision: 3 February 2000

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Suga, S., Kanno, T., Ogawa, Y. et al. cAMP-independent decrease of ATP-sensitive K+ channel activity by GLP-1 in rat pancreatic β-cells.Pflügers Arch - Eur J Physiol 440, 566–572 (2000). https://doi.org/10.1007/s004240000279

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