Impact of biotin supplemented diet on mouse pancreatic islet beta-cell mass expansion and glucose induced electrical activity

Abstract

Biotin supplemented diet (BSD) is known to enhance beta-cell replication and insulin secretion in mice. Here, we first describe BSD impact on the islet beta-cell membrane potential (Vm) and glucose-induced electrical activity. BALB/c female mice (n >= 20) were fed for nine weeks after weaning with a control diet (CD) or a BSD (100X). In both groups, islet area was compared in pancreatic sections incubated with anti-insulin and anti-glucagon antibodies; Vm was recorded in micro dissected islet beta-cells during perfusion with saline solutions containing 2.8, 5.0, 7.5-, or 11.0 mM glucose. BSD increased the islet and 13-cell area compared with CD. In islet beta-cells of the BSD group, a larger Delta Vm/Delta[glucose] was found at sub-stimulatory glucose concentrations and the threshold glucose concentration for generation of action potentials (APs) was increased by 1.23 mM. Moreover, at 11.0 mM glucose, a significant decrease was found in AP amplitude, frequency, ascending and descending slopes as well as in the calculated net charge influx and efflux of islet beta-cells from BSD compared to the CD group, without changes in slow Vm oscillation parameters. A pharmacological dose of biotin in mice increases islet insulin cell mass, shifts islet beta-cell intracellular electrical activity dose response curve toward higher glucose concentrations, very likely by increasing KATP conductance, and decreases voltage gated Ca2+ and K+ conductance at stimulatory glucose concentrations.