Factors determining the glucose sensitivity and glucose responsiveness of pancreatic beta cells.
Functional, metabolic and molecular studies using purified beta cells (beta-cell have contributed to our understanding how insulin synthesis and release at regulated by glucose. Individual rat islet beta-cells are heterogeneous in the threshold sensitivity to glucose, so that the physiological graded glucose induced response of the pancreatic beta-cell population can be explained--at least in part--by dose-dependent recruitment of cells. beta-Cell threshold sensitivity to glucose is correlated to glucokinase gene expression rather than glucose transport, reinforcing the concept that glucokinase is directly involved in beta-cell glucose sensing. This idea is further supported by observing major species differences in islet GLUT2 expression, whereas islet cell glucokinase expression and function are strongly conserved. Studies on pure rat beta-cell have also shown that cyclic AMP acts--in addition to its well-known potentiator function of glucose-induced insulin release--as a competence factor which is absolutely required for normal beta-cell responsiveness to glucose. Intraislet glucagon appears to be a paracrine regulator of cyclic AMP production in vitro, but this signalling pathway can be an artifact of the islet isolation procedure. In rat beta-cells, expression and functional activity can be demonstrated on receptors recognising glucagon, glucagon-like peptide I and glucose-dependent insulinotropic peptide. Whether this diversity in signalling reflects another form of beta-cell heterogeneity, functional complementation or biological redundancy, remains to be investigated.
Department of Biochemistry, Diabetes Research Centre, Vrije Universiteit Brussels, Belgium.
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D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D051273:Glucose Transporter Type 2; D006593:Hexokinase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
D051273:Glucose Transporter Type 2; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D000242:Cyclic AMP; D006593:Hexokinase; D005947:Glucose