Fig. 2: BBR increases insulin secretion in high-fat diet (HFD)-fed hyperglycemic mice but not in Kcnh6 global knockout (KO) or Kcnh6 islet β-cell-specific knockout (βKO) hyperglycemic mice.

a–e HFD-fed mice and Kcnh6 KO mice were orally administered 560 mg/kg BBR or vehicle before being loaded with 1 g/kg glucose for the intraperitoneal glucose tolerance test (IPGTT) and insulin release test (IRT). a Blood glucose (control, n = 8; BBR, n = 7, P = 0.009) and b plasma insulin (control, n = 5; BBR, n = 5, P = 0.016) levels in HFD-fed mice. c Kcnh6 KO mice were generated using the TALEN technique. Two TALENs specifically binding the target sequences in exon 5 of the Kcnh6 gene resulted in the knockout of the gene. Western blot analysis of the KCNH6 protein from WT and KO mouse islets. A representative immunoblot from 3 different experiments is shown. d Blood glucose (control, n = 10; BBR, n = 7) and e plasma insulin (control, n = 9; BBR, n = 8) levels in Kcnh6 KO mice. f–j Chow diet-fed control and Kcnh6 βKO mice were orally administered 560 mg/kg BBR or vehicle before being loaded with 3 g/kg glucose for the IPGTT and IRT. f Blood glucose (control, n = 6; BBR, n = 4, P = 0.038) and g plasma insulin (control, n = 10; BBR, n = 8, P = 0.012) levels in chow diet-fed control mice. h Kcnh6 βKO mice were generated using the CRISPR-mediated Cre-LoxP recombinase system. The endogenous Kcnh6 locus was targeted for the conditional excision of exons 3 and 4. Western blot analysis of the KCNH6 protein from control and βKO mouse islets. A representative immunoblot from three different experiments is shown. i Blood glucose (control, n = 4; BBR, n = 4) and j plasma insulin (control, n = 4; BBR, n = 4) levels in Kcnh6 βKO mice. The values are presented as means ± s.e.m. *P < 0.05 and **P < 0.01. Statistical significance was assessed using the Mann–Whitney U-test (two-sided).