INDIVIDUAL BETA-CELLS WITHIN THE INTACT ISLET DIFFERENTIALLY RESPOND TO GLUCOSE

Insulin production by the pancreatic islet is tightly coupled to the c oncentration 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 is lets using adenovirus gene transfer and direct observation of insulin promoter-directed green fluorescent protein activity indicates that be ta cells are functionally heterogeneous. An increase in glucose concen tration not only stimulates expression within individual beta cells, b ut unexpectedly acts to increase the total number of positive cells. T he net islet response to a given glucose stimulus reflects an integrat ed action of beta cells with individually differing behaviors. This ad ditional level of functional complexity may provide new insights into the pathophysiology and treatment of diabetes mellitus.