Plasma membrane depolarization as a determinant of the first phase of insulin secretion

K Hatlapatka, M Willenborg… - American Journal of …, 2009 - journals.physiology.org
K Hatlapatka, M Willenborg, I Rustenbeck
American Journal of Physiology-Endocrinology and Metabolism, 2009journals.physiology.org
The role of plasma membrane depolarization as a determinant of the initial phase of insulin
secretion was investigated. NMRI mouse islets and β-cells were used to measure the
kinetics of insulin secretion, ATP and ADP content, membrane potential, and cytosolic free
Ca2+ concentration ([Ca2+] i). The depolarization of metabolically intact β-cells by KCl
corresponded closely to the theoretical values. In contrast to physiological (glucose) or
pharmacological (tolbutamide) ATP-sensitive K+ (KATP) channel block, KCl depolarization …
The role of plasma membrane depolarization as a determinant of the initial phase of insulin secretion was investigated. NMRI mouse islets and β-cells were used to measure the kinetics of insulin secretion, ATP and ADP content, membrane potential, and cytosolic free Ca2+ concentration ([Ca2+]i). The depolarization of metabolically intact β-cells by KCl corresponded closely to the theoretical values. In contrast to physiological (glucose) or pharmacological (tolbutamide) ATP-sensitive K+ (KATP) channel block, KCl depolarization did not induce action potential spiking. The depolarization by 15 mM K+ (21 mV) corresponded to the plateau depolarization by 50 or 500 μM tolbutamide; that by 40 mM K+ (41 mV) corresponded to the action potential peaks. Nifedipine and diazoxide abolished action potentials but not KCl depolarization, suggesting that the depolarizing strength of 15, but not 40 mM K+ corresponds to that of KATP channel closure. K+ (40 mM) induced a massive secretory response in the presence of 5 mM glucose, whereas 15 mM K+, like 50 μM tolbutamide, was only slightly effective, even though a marked increase in [Ca2+]i was produced. Raising glucose from 5 to 10 mM in the continued presence of 15 mM K+ resulted in a strongly enhanced biphasic response. The depolarization pattern of this combination could be mimicked by combining basal glucose with 15 mM K+ and 50 μM tolbutamide; however, the secretory response to these nonnutrients was much weaker. In conclusion, the initial secretory response to nutrient secretagogues is largely influenced by signaling mechanisms that do not involve depolarization.
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