DEVELOPMENTAL GENE-EXPRESSION IN THE HUMAN FETAL PANCREAS

Differential developmental regulation of pancreas-specific genes has n ot been reported for the human fetal pancreas. We have therefore under taken a systematic, quantitative analysis of the transcriptional level s of various genes in the human pancreas at different stages of fetal and postnatal development. Using sensitive ribonuclease protection ass ays, in situ hybridization, and the polymerase chain reaction, our res ults indicate the following: 1) Transcriptional levels of insulin and amylin remain lower in the fetal than in the adult pancreas, whereas g lucagon and somatostatin mRNA levels are consistently greater after 14 wk gestation than postnatally. These results are in agree ment with p revious immunohistochemical studies of these gene products. 2) The reg gene exhibits a 20-fold increase in mRNA levels after 16 wk gestation . The gene is expressed exclusively in the acinar cells and does not c olocalize with insulin. This restricted exocrine expression does not i ndicate a direct role for the reg gene in islet development. 3) Glucos e transporter 2 and glucokinase mRNA are detectable as early as 13 wk gestation and remain low throughout development. Glucose transporter 1 reaches adult transcriptional levels by 18 wk gestation. The early de tection of glucose transporter 2 and glucokinase implies that lack of expression of these ''glucose sensor'' genes does not account for the known insensitivity of the fetal beta-cells to glucose.