Dipeptidyl peptidase-4 expression in pancreatic tissue from patients with congenital hyperinsulinism.
Congenital hyperinsulinism (CHI) is caused by unregulated insulin release and leads to hyperinsulinaemic-hypoglycaemia (HH). Glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) and the enzyme; dipeptidyl peptidase-4 (DPP-4) all regulate appetite and glucose homeostasis. These proteins have been identified as possible contributors to HH but the mechanism remains poorly understood. We aimed to look at the expression pattern of pancreatic DPP-4 in children with focal and diffuse CHI (FCHI and DCHI, respectively). Using immunohistochemistry; we determined DPP-4 expression patterns in the pancreas of CHI patients. DPP-4 was found to be expressed in the pancreatic β, α and δ-cells in and around the focal area. However, it was predominantly co-localised with β-cells in the paediatric tissue samples. Additionally, proliferating β-cells expressed DPP-4 in DCHI, which was absent in the FCHI pancreas. Insulin was found to be present in the exocrine acini and duct cells of the DCHI pancreas suggestive of exocrine to endocrine transdifferentiation. Furthermore, 6 medically-unresponsive DCHI pancreatic samples showed an up-regulation of total pancreatic DPP-4 expression. In conclusion; the expression studies have shown DPP-4 to be altered in HH, however, further work is required to understand the underlying role for this enzyme.
Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health & Disease Section, UCL Institute of Child Health & Great Ormond Street Hospital 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Sofia A
SA
Rahman
Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health & Disease Section, UCL Institute of Child Health & Great Ormond Street Hospital 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Senthil
S
Senniappan
Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health & Disease Section, UCL Institute of Child Health & Great Ormond Street Hospital 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Maha
M
Sherif
Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health & Disease Section, UCL Institute of Child Health & Great Ormond Street Hospital 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Sophia
S
Tahir
Genetics and Genomic Medicine Programme, Genetics and Epigenetics in Health & Disease Section, UCL Institute of Child Health & Great Ormond Street Hospital 30 Guilford Street, London, WC1N 1EH, United Kingdom.
Khalid
K
Hussain
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D044903:Congenital Hyperinsulinism / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D018819:Dipeptidyl Peptidase 4 / Q000032:analysis* / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D050417:Insulin-Secreting Cells / Q000201:enzymology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D015854:Up-Regulation
D015415:Biomarkers; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
CHI; DPP-4; hypoglycaemia