Cooling dissociates glucose‐induced insulin release from electrical activity and cation fluxes in rodent pancreatic islets.

Abstract

SUMMARY1. Insulin release and fl-cell membrane potentials in response to glucose at 37 and 27 TC have been measured simultaneously in single, micro-dissected, perifused islets of Langerhans from normal mice.2. Insulin release and 45Ca outflow in response to glucose at 37 and 27 'C have been measured simultaneously from perifused islets isolated by collagenase digestion from normal rats.3. The effect of cooling on fl-cell membrane potassium permeability was assessed by changes in measured membrane potential and input resistance (in the mouse) and by changes in 86Rb outflow (in the rat).4. Resting and active fl-cell membrane parameters (i.e. membrane potential, spike frequency, input resistance, 45Ca outflow and 86Rb outflow), in both mouse and rat islets, were affected only slightly by cooling to 27 'C, with temperature coefficients of 2 or lower.5. At 27 'C glucose-stimulated insulin release was inhibited completely in mouse islets and almost completely in rat islets. The temperature coefficients in both preparations were greater than 5.6. It is concluded that #-cell electrical activity and changes in membrane permeability induced by glucose are not consequences of insulin release.

Differentiation of nestin-positive cells derived from bone marrow into pancreatic endocrine and ductal cells in vitro

“…5 ng/100 spheroids per hour respectively. This is consistent with inhibition of glucose-induced insulin release by cooling (Atwater et al 1984). These findings demonstrate de novo synthesis and processing of insulin and physiologically regulated secretion.…”

Insulin Feedback Alters Mitochondrial Activity Through an ATP-sensitive K+ Channel–Dependent Pathway in Mouse Islets and β-Cells

“…Although these changes may be due to the nonspecific effects of cooling, they would also, in fact, be expected if cooling inhibited K ATP channel opening after the suppression of insulin secretion within the islet. We have quantitatively tested this hypothesis using a computer simulation in which the effect of cooling was modeled as an 8% reduction in maximal K ATP conductance (R. Bertram and A. Sherman, unpublished observations) and found that indeed this resulted in qualitatively similar changes in bursting to those reported by Atwater et al (46) and Debuyser et al (47). Although this does not prove our hypothesis that secreted insulin activates K ATP channels in mouse islets, these classic temperature experiments do not rule out the hypothesis.…”

“…A general objection to the hypothesis that secreted insulin functionally modulates glucose-induced bursting via K ATP channel activation is the observation that inhibiting islet insulin secretion by cooling islets from 37 to 20 -27°C does not abolish glucose-induced bursting (46,47). This suggests that secreted insulin must therefore not be required for islet bursting to occur.…”

Bursting electrical activity in pancreatic beta cells caused by Ca(2+)- and voltage-inactivated Ca2+ channels.

“…2A. This change, however, is more "normal" (32) in that normal bursting can be recovered by a small increase in rin (e.g., from 20 ms to 20.7 ms). This is caused by a shift in the Hopf bifurcation point on the upper branch, whose location is sensitive to both GATP and T, Larger values of Tn.-e.g., 22 ms-shift the Hopf bifurcation curve so far to the left that only the "beating" type spiking is observed.…”