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Abstract

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 þ 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 þ 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 þ ATP channel labelling was detected in an increasing proportion of insulin-positive cells and epithelial labelling with K þ 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.

Dynamics and Regulation of Insulin Secretion in Pancreatic Islets from Normal Young Children

“…Only the half-maximally effective glucose concentration was slightly higher in infant than adult islets (G 7–8.5 versus G 6.5–7). These adult-type responses to glucose indirectly indicate that metabolism of the sugar is also controlled by glucokinase rather than hexokinase-I [28, 43, 44] in infant β-cells.…”

Human Pancreas Endocrine Cell Populations and Activating <b><i>ABCC8</i></b> Mutations

“…In human fetuses, K ATP channels were identified in a subpopulation of pancreatic epithelial cells at 10 weeks of gestation but not in β cells before 16 weeks of gestation. At 15 weeks of gestation, K ATP channel subunits did not co-localise with glucagon or somatostatin [16]. K ATP channels are functional as early as 14 weeks of gestation in humans but do not respond to glucose [17].…”

Hyperinsulinism and Diabetes: Genetic Dissection of β Cell Metabolism-Excitation Coupling in Mice

“…Although both GLUT1 and GLUT2 isoforms may be present in human islets (Richardson et al, 2007). GLUT2 is the main isoform expressed in rodent pancreatic β-cells (Efrat et al, 1994; Thorens, 2001).…”