TY - JOUR
T1 - Accounting for near-normal glucose sensitivity in Kir6.2[AAA] transgenic mice
AU - Tsaneva-Atanasova, Krasimira
AU - Sherman, Arthur
N1 - Funding Information:
A.S. was supported by the intramural research program of the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
PY - 2009/11/4
Y1 - 2009/11/4
N2 - Kir6.2[AAA] transgenic mouse islets exhibit mosaicism such that ∼70% of the β-cells have nonfunctional ATP-sensitive potassium (K ATP) channels, whereas the remainder have normal KATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by ∼2 mM. We use a previously published mathematical model, in which KATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of KATP conductance. Compensation is favored by the assumption that only a small fraction of KATP channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets.
AB - Kir6.2[AAA] transgenic mouse islets exhibit mosaicism such that ∼70% of the β-cells have nonfunctional ATP-sensitive potassium (K ATP) channels, whereas the remainder have normal KATP function. Despite this drastic reduction, the glucose dose-response curve is only shifted by ∼2 mM. We use a previously published mathematical model, in which KATP conductance is increased by rises in cytosolic calcium through indirect effects on metabolism, to investigate how cells could compensate for the loss of KATP conductance. Compensation is favored by the assumption that only a small fraction of KATP channels are open during oscillations, which renders it easy to upregulate the open fraction via a modest elevation of calcium. We show further that strong gap-junctional coupling of both membrane potential and calcium is needed to overcome the stark heterogeneity of cell properties in these mosaic islets.
UR - http://www.scopus.com/inward/record.url?scp=72249088260&partnerID=8YFLogxK
U2 - 10.1016/j.bpj.2009.07.060
DO - 10.1016/j.bpj.2009.07.060
M3 - Article
AN - SCOPUS:72249088260
SN - 0006-3495
VL - 97
SP - 2409
EP - 2418
JO - Biophysical Journal
JF - Biophysical Journal
IS - 9
ER -