Increased insulin secretion during the later stages of pregnancy is important for metabolic stability in the material compartment in the face of nutrient demands by the fetus. The islets of Langerhans undergo major alterations in structure and function in order to accommodate the increased demand for insulin. These changes include: 1) The threshold for glucose stimulated insulin secretion is decreased; 2) The above threshold insulin secretion is enhanced; 3) Dye coupling among B-cells is increased; and 4) The islet volume is increased. Based on our studies with prolactin, we have proposed that it is lactogenic activity which induced these changes. Using lactogen treated islets in culture as a model for studying the changes which occur in islets during pregnancy, we prose to: 1) Determine the effect of placental lactogen in vitro on insulin secretion, junctional coupling, insulin content, islet cell growth and cell division; 2) Determine the lactogen induced changes in B-cell metabolism which lead to altered insulin secretion; 3) Determine the lactogen changes in B-cell metabolism which lead to increased dye coupling; and 4) Determine the relationship between alterations B-cell coupling and insulin secretion. This in vitro model of islets during pregnancy provides a unique opportunity to study major alterations of B-cell structure and function in response to a normal physiological condition. Studies based on this model will not only provide important information about mechanisms of B-cell response to pregnancy, but also aid in determining the function of B-cell junctional coupling and the relevant changes in B-cell metabolism which regulate insulin secretion. Our studies should provide a basis for investigating the causes and/or consequences of inadequate insulin secretion in pregnancy, as may occur in certain forms of gestational diabetes.
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