Blood insulin levels are normally elevated during pregnancy and lactation, but the mechanisms responsible for the hyperinsulinemia are unclear. Preliminary results from our laboratories have suggested the possibility of the following mechanism: 1. lactogens act as endocrine signals that elicit increased junctional coupling among B-cells in the pancreatic islets, and 2. the lactogen-induced coupling leads to a decreased threshold for glucose-stimulated insulin secretion and a greater insulin secretion at suprathreshold glucose levels. In a collaboration of three laboratories, we propose to test this hypothesis by exploiting our respective expertise in the techniques of intracellular dye injection and freeze-fracture, pancreas perfusion, and radioimmunoassay and bioassay of lactogens and islet hormones.
Our specific aims are to: 1. determine the quantitative changes in B-cell dye coupling (and gap junctions) and in islet hormone secretion as a function of the concentration of lactogen given to islets and perfused pancreata in vitro, infused via osmotic pumps in vivo, and altered naturally during pregnancy, lactation, and postlactation; 2. determine the glucose-dependency of the lactogen effects on coupling in vitro; and 3. determine the cell contact (and cell coupling) dependency of the lactogen effects on insulin secretion in vitro. These experiments should be important in providing: 1. new information about a possible mechanism by which the islet responds to the increased demand for insulin during pregnancy and lactation; 2. a physiological correlate for junctional communication among B-cells; and 3. a basis for future investigations into the consequences or causes of inadequate insulin secretion in pregnancy, as may, for example, occur in certain forms of gestational diabetes.
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