Insulin secretion in health and disease: genomics, proteomics and single vesicle dynamics.
Defective insulin secretion from pancreatic islet beta-cells is a sine qua non of Type II (non-insulin-dependent) diabetes. Digital imaging analysis of the nanomechanics of individual exocytotic events, achieved using total internal reflection fluorescence microscopy, has allowed us to demonstrate that insulin is released via transient or 'cavicapture' events whereby the vesicle and plasma membranes fuse transiently and reversibly. Such studies reveal that an increase in the number of abortive fusion events contributes to defective insulin secretion in in vitro models of Type II diabetes. Complementary analyses of genome-wide changes in beta-cell gene expression, at both the mRNA and protein levels, are now facilitating the identification of key molecular players whose altered expression may contribute to the secretory defects in the diabetic beta-cell.
Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol BS8 1TD, UK. g.a.rutter@bris.ac.uk
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Rutter
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Varadi
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Tsuboi
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Parton
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Ravier
D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism*; D023281:Genomics; D005947:Glucose / Q000378:metabolism; D006262:Health; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D040901:Proteomics
D007328:Insulin; D005947:Glucose