biostudies-arrayexpressMuhammad FauziMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-15682Intracellular Ca2+ dynamics represent a key mechanism in glucose-induced insulin secretion (GIIS) and hepatic glucose production (HGP). In this study, we demonstrated that Car8wdl mice, a global carbonic anhydrase VIII (CA8)-deficient model, had increased GIIS and moderate HGP elevation in vivo and ex vivo. These phenotypes were mediated by the enhancement of inositol-3-phosphate receptor 1 (IP3R1)-facilitated Ca2+ release attributable to the absence of CA8. In the isolated CA8-deficient hepatocytes, increased gluconeogenic gene expression was detected, and the enhancement of HGP was not attenuated by PKA and PLC inhibitor treatment. In ob/ob mice, CA8 expression was increased in pancreatic islets but decreased in hepatocytes, whereas hepatic CA8 overexpression reduced glucagon-induced HGP and normalized excessive HGP. Additionally, HGP was reduced in human hepatocytes by overexpressing CA8. In conclusion, CA8 is a common regulator of GIIS and HGP via IP3R1-mediated Ca2+ release therefore has a coordinating role on postprandial and fasting conditions. This study provided a key to understanding the complexity of the pathogenesis of type 2 diabetes and identified potential therapeutic strategies.biostudies-arrayexpressSample Collection - Mouse hepatocytes were cultured overnight, fasted 2 hours, and incubated with 1 mM lactate and 10 mM pyruvate for 4 hours.Library Construction - Poly(A) mRNA was isolated using Oligo(dT) beads, fragmented with divalent cations and high heat, and primed with random primers. First- and second-strand cDNA were synthesized, followed by end repair, dA-tailing, and T-A adaptor ligation. Adaptor-ligated DNA was size-selected with DNA Clean Beads and amplified via PCR using P5 and P7 primers.Sequencing - The indexed libraries were multiplexed and sequenced on an Illumina HiSeq/Novaseq or MGI2000 using a 2 × 150 PE configuration according to the manufacturer’s instructions.Nucleic Acid Extraction - RNA was extracted using Rneasy minikit (Qiagen), 1 microgram of total RNA was utilized for library construction.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - FPKM are calculated from the number of reads that mapped to each particular gene sequence taking into account the gene length (one expects more reads to be produced from longer genes) and the sequencing depth (one expects more reads to be produced from the sample that has been sequenced to a greater depth).MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina HiSeq 1000RNA-seq of coding RNAMus musculusMuhammad FauziTakaaki MurakamifalseCarbonic anhydrase VIII regulates glucose-induced insulin secretion and hepatic glucose production via IP3R1-mediated Ca2+ releaseIntracellular Ca2+ dynamics represent a key mechanism in glucose-induced insulin secretion (GIIS) and hepatic glucose production (HGP). In this study, we demonstrated that Car8wdl mice, a global carbonic anhydrase VIII (CA8)-deficient model, had increased GIIS and moderate HGP elevation in vivo and ex vivo. These phenotypes were mediated by the enhancement of inositol-3-phosphate receptor 1 (IP3R1)-facilitated Ca2+ release attributable to the absence of CA8. In the isolated CA8-deficient hepatocytes, increased gluconeogenic gene expression was detected, and the enhancement of HGP was not attenuated by PKA and PLC inhibitor treatment. In ob/ob mice, CA8 expression was increased in pancreatic islets but decreased in hepatocytes, whereas hepatic CA8 overexpression reduced glucagon-induced HGP and normalized excessive HGP. Additionally, HGP was reduced in human hepatocytes by overexpressing CA8. In conclusion, CA8 is a common regulator of GIIS and HGP via IP3R1-mediated Ca2+ release therefore has a coordinating role on postprandial and fasting conditions. This study provided a key to understanding the complexity of the pathogenesis of type 2 diabetes and identified potential therapeutic strategies.2026-09-01T00:00:00Z2026-09-01T04:20:01.364Z2025-11-11T17:17:20.431ZE-MTAB-15682ERP181283EFO_0002944EFO_0004170EFO_0005518EFO_0003816EFO_0003738EFO_0004184