Abstract
Insulin production by the pancreatic islet is tightly coupled to the concentration of blood glucose. The mechanism by which glucose controls proinsulin biosynthesis in beta cells is poorly understood. Analysis of insulin gene expression in individual cells within whole, living islets using adenovirus gene transfer and direct observation of insulin promoter-directed green fluorescent protein activity indicates that beta cells are functionally heterogeneous. An increase in glucose concentration not only stimulates expression within individual beta cells, but unexpectedly acts to increase the total number of positive cells. The net islet response to a given glucose stimulus reflects an integrated action of beta cells with individually differing behaviors. This additional level of functional complexity may provide new insights into the pathophysiology and treatment of diabetes mellitus.
Highlights
Glucose stimulates both insulin secretion and proinsulin biosynthesis through signals associated with its metabolism in the  cell of the pancreatic islet [1,2,3]
These results established that the glucose induction of the insulin promoter could be detected after gene transfer into the whole islet, only the net islet response and not the contributions of individual  cells was measured
In terms of insulin promoter activity, functional  cell heterogeneity in the context of the intact islet provides an additional level of organizational complexity
Summary
Glucose stimulates both insulin secretion and proinsulin biosynthesis through signals associated with its metabolism in the  cell of the pancreatic islet [1,2,3]. Studies measuring aggregate responses of clonal, insulinoma cells or dispersed islet cells in culture have demonstrated that glucose stimulates insulin gene transcription through activation of the insulin promoter (4 –11). Isolated rat islets were treated with a recombinant, type 5 adenovirus (see “Experimental Procedures”), which contains the rat Ins promoter [35] directing the expression of the lacZ (-galactosidase) reporter gene (AdIns--gal).
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