File:11154 2020 9548 Fig1 HTML.webp

English: Diagrammatic representation of β-cell function. Genetic defects associated with CHH are included in red. Postprandial glucose is taken into the β-cells via the glucose transporter 2 (GLUT2). Glucose then enters the glycolysis pathway followed by mitochondrial citric acid cycle (TCA) yielding the high-energy molecule, adenosine triphosphate (ATP). ATP molecules travel to and inhibit the potassium-dependent ATP channels (KATP), which prevents influx of potassium resulting in membrane depolarization. This triggers voltage-gated calcium channels to open and influx of calcium (Ca2+) occurs. The Ca2+ activates the enzyme phospholipase C (PLC) to produce inositol 1, 3, 5 triphosphate (IP3) and diacylglycerol (DAG) from phosphatidyl 1, 3 bisphosphate (PIP2). The IP3 molecule binds to the protein receptor on the endoplasmic reticulum (ER) to promote a release of Ca2+ from the ER. This subsequently increase in cytoplasmic Ca2+ promotes exocytosis of the pre-packaged mature insulin and active C-peptide, which are released into circulation. GLUT2: Glucose transporter 2; Glucokinase (GCK) encoded by GCK gene; ADP: Adenosine diphosphate; ATP: Adenosine triphosphate; Monocarboxylate transporter (MCT1) encoded by SLC16A1 gene; Glutamate dehydrogenase (GDH) encoded by GLUD1 gene; Uncoupling protein 2 (UCP2) encoded by UCP2 gene; L-3-hydroxyacyl-coenzyme A dehydrogenase (HADH) encoded by HADH gene; SUR1 subunit of the KATP channel encoded by the ABCC8 gene; Kir6.2 subunit of the KATP channel encoded by KCNJ11 gene; Hepatocyte nuclear factor 4α (HNF4α) encoded by HNF4A gene; Hepatocyte nuclear factor 1α (HNF1α) encoded by HNF1A gene; HK1: Hexokinase 1 encoded by the gene HK1; CACNA1D: calcium voltage-gated channel subunit alpha1 D. Mutations in Forkhead Box Protein A2 (FOXA2), Phosphoglucomutase 1 (PGM1) and Phosphomannomutase 2 (PMM2) are not included in the cartoon.