High fructose consumption leads to increases in glucagon secretion and α-cell expansion. A: glucagon secretion from cultured islets under low (1 mM) and high glucose (16.7 mM) with or without 20 mM l-arginine; n = 5 replicates of islet batches from 4 mice in each group. B: total islet glucagon content; n = 12 batches of islets. C: representative immunofluorescence image of control and HFr islets. Green, insulin; red, glucagon. D: quantification of Ki-67-positive red stained α-cells (left) and representative image (right). Red, glucagon; yellow, Ki-67; Dapi, blue (n = 3 mice pancreata examined by pancreatic sections separated by 80 µm from each of 3 mice). **P < 0.01 and ***P < 0.001 by Student’s t-test.