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Cells within the Intact Islet Differentially
Respond to Glucose
(Received for publication, July 28, 1997)
,
,
and¶
From the Department of Insulin production by the pancreatic islet is
tightly coupled to the concentration of blood glucose. The mechanism by
which glucose controls proinsulin biosynthesis in 
Medicine and Department of
¶ Physiology, New England Medical Center and Tufts University
School of Medicine, Boston, Massachusetts 02111
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 cells are functionally heterogeneous. An
increase in glucose concentration not only stimulates expression within
individual 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 cells with individually
differing behaviors. This additional level of functional complexity may
provide new insights into the pathophysiology and treatment of diabetes
mellitus.
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