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Gunawardana SC, Rocheleau JV, Head WS, et al. Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH. BMC Endocr Disord. 2004;4(1):1doi: 10.1186/1472-6823-4-1.
Gunawardana, S. C., Rocheleau, J. V., Head, W. S., & Piston, D. W. (2004). Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH. BMC endocrine disorders, 4(1), 1. https://doi.org/10.1186/1472-6823-4-1
Gunawardana, Subhadra C, et al. "Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH." BMC endocrine disorders vol. 4,1 (2004): 1. doi: https://doi.org/10.1186/1472-6823-4-1
Gunawardana SC, Rocheleau JV, Head WS, Piston DW. Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH. BMC Endocr Disord. 2004 Jun 11;4(1):1. doi: 10.1186/1472-6823-4-1. PMID: 15193158; PMCID: PMC434517.
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BMC Endocr Disord. 2004 Jun 11;4(1):1. doi: 10.1186/1472-6823-4-1.

Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH.

BMC endocrine disorders

Subhadra C Gunawardana, Jonathan V Rocheleau, W Steven Head, David W Piston

Affiliations

  1. Department of Molecular Physiology and Biophysics, 702 Light Hall, Vanderbilt University, Nashville, TN 37232, USA. [email protected]

PMID: 15193158 PMCID: PMC434517 DOI: 10.1186/1472-6823-4-1

Abstract

BACKGROUND: Many mechanistic steps underlying nutrient-stimulated insulin secretion (NSIS) are poorly understood. The influence of intracellular pH (pHi) on insulin secretion is widely documented, and can be used as an investigative tool. This study demonstrates previously unknown effects of pHi-alteration on insulin secretion in mouse islets, which may be utilized to correct defects in insulin secretion. METHODS: Different components of insulin secretion in mouse islets were monitored in the presence and absence of forced changes in pHi. The parameters measured included time-dependent potentiation of insulin secretion by glucose, and direct insulin secretion by different mitochondrial and non-mitochondrial secretagogues. Islet pHi was altered using amiloride, removal of medium Cl-, and changing medium pH. Resulting changes in islet pHi were monitored by confocal microscopy using a pH-sensitive fluorescent indicator. To investigate the underlying mechanisms of the effects of pHi-alteration, cellular NAD(P)H levels were measured using two-photon excitation microscopy (TPEM). Data were analyzed using Student's t test. RESULTS: Time-dependent potentiation, a function normally absent in mouse islets, can be unmasked by a forced decrease in pHi. The optimal range of pHi for NSIS is 6.4-6.8. Bringing islet pHi to this range enhances insulin secretion by all mitochondrial fuels tested, reverses the inhibition of glucose-stimulated insulin secretion (GSIS) by mitochondrial inhibitors, and is associated with increased levels of cellular NAD(P)H. CONCLUSIONS: Pharmacological alteration of pHi is a potential means to correct the secretory defect in non-insulin dependent diabetes mellitus (NIDDM), since forcing islet pHi to the optimal range enhances NSIS and induces secretory functions that are normally absent.

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