AIMS/HYPOTHESIS: Although cells expressing insulin are detected early in human fetal development, islets isolated from fetal pancreases show poor insulin secretory responses to glucose, which may be the result of deficient glucose sensing. We have used dual and triple immunolabelling of human fetal and adult pancreas sections to investigate the presence of proteins that participate in glucose sensing in the pancreatic beta cell, namely glucose transporter 1 (GLUT 1, also known as SLC2A1), glucose transporter 2 (GLUT2, also known as SLC2A2), glucokinase (GCK) and inwardly rectifying K+ channel (KIR6.2, also known as KCNJ11) and sulphonylurea receptor 1 (SUR1, also known as ABCC8) subunits of ATP-sensitive K+ channels (K+(ATP) channels). MATERIALS AND METHODS: Pancreases obtained with ethical approval from human fetuses from 11 to 36 weeks of gestation, from infants and from adults were formalin-fixed and embedded in paraffin. Sections were labelled with antibodies to proteins of interest. Co-production of antigens was examined by dual and triple immunolabelling. RESULTS: GLUT2 and K+(ATP) channel labelling was detected in the 11-week pancreas, but largely within the pancreatic epithelium, whereas no labelling for GLUT1 was observed. From 15 weeks, GLUT1, GCK and K+(ATP) channel labelling was detected in an increasing proportion of insulin-positive cells and epithelial labelling with K+(ATP) channel antibodies diminished. GLUT2 was seen in the majority of beta cells only after 7 months of age. CONCLUSIONS/ INTERPRETATION: The results demonstrate that only a subpopulation of beta cells in the human fetal pancreas produce all key elements of the glucose-sensing apparatus, which may contribute to poor secretory responses in early life.
AIMS/HYPOTHESIS: Although cells expressing insulin are detected early in human fetal development, islets isolated from fetal pancreases show poor insulin secretory responses to glucose, which may be the result of deficient glucose sensing. We have used dual and triple immunolabelling of human fetal and adult pancreas sections to investigate the presence of proteins that participate in glucose sensing in the pancreatic beta cell, namely glucose transporter 1 (GLUT 1, also known as SLC2A1), glucose transporter 2 (GLUT2, also known as SLC2A2), glucokinase (GCK) and inwardly rectifying K+ channel (KIR6.2, also known as KCNJ11) and sulphonylurea receptor 1 (SUR1, also known as ABCC8) subunits of ATP-sensitive K+ channels (K+(ATP) channels). MATERIALS AND METHODS: Pancreases obtained with ethical approval from human fetuses from 11 to 36 weeks of gestation, from infants and from adults were formalin-fixed and embedded in paraffin. Sections were labelled with antibodies to proteins of interest. Co-production of antigens was examined by dual and triple immunolabelling. RESULTS: GLUT2 and K+(ATP) channel labelling was detected in the 11-week pancreas, but largely within the pancreatic epithelium, whereas no labelling for GLUT1 was observed. From 15 weeks, GLUT1, GCK and K+(ATP) channel labelling was detected in an increasing proportion of insulin-positive cells and epithelial labelling with K+(ATP) channel antibodies diminished. GLUT2 was seen in the majority of beta cells only after 7 months of age. CONCLUSIONS/ INTERPRETATION: The results demonstrate that only a subpopulation of beta cells in the human fetal pancreas produce all key elements of the glucose-sensing apparatus, which may contribute to poor secretory responses in early life.
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