Sorenson's research focuses on the long term modulating effects of pregnancy on pancreatic islets of Langerhans. Although rapid regulation of insulin secretion by nutrients and hormones has been the focus of considerable research, the examination of long-term modulation of islets has received much less attention. Pregnancy is a normally occurring physiological condition where there is a long term need for increased insulin secretion at normal serum glucose levels. This demand is met by many major alterations in islet structure and function. Among these changes the most important are: (a) an increase in glucose-stimulated insulin secretion (4-10 fold at normal serum glucose concentrations); (b) a lowering of the glucose-stimulation threshold; and (c) increased ß-cell proliferation. Using species specific lactogenic hormones (placental lactogen and prolactin which share a common receptor) Sorenson and his lab have demonstrated that these hormones induce all of the known changes in islets that occur during pregnancy.
Using islets from pregnancy and islets treated with lactogenic hormones in vitro the lab is investigating: (1) The signal transduction pathways used by prolactin receptors in islets. (2) How the lactogen induced changes in gene expression lead to enhanced insulin secretion. (3) How the lactogen induced changes in metabolism lead to enhanced insulin secretion. (4) How lactogens stimulate ß-cell proliferation. (5) The role of lactogens in the development and growth of islets. (6) The glucose dependence of the lactogen induced changes in vivo and how these changes compare with those induced by in vivo glucose infusion. Although mechanisms of lactogen regulation of islets will likely share some features with other prolactin sensitive cells, they will also be very unique as they must include features for affecting the islet specific metabolic sensing system. The Sorenson lab's long term goal is to delineate the mechanisms responsible for the increased islet function observed during pregnancy.
These studies will provide important information on the long term regulation of islet function and ß-cell mass. Understanding the regulation of ß-cell glucose sensitivity has important implications for understanding the progression of events that lead to gestational and type II diabetes. In addition, the studies on regulation of islet ß-cell growth will provide essential information on development of ß-cells and the growth potential of differentiated islet ß-cells.
Selected Publications (Pubmed Search)
R.L. Sorenson and T.C. Brelje, (2009) Prolactin Receptors are Critical to the Adaptation of Isets to Pregnancy. Endocrinology 150:1566-1569
T.C. Brelje, NV Bhagroo. L.E. Sout and R.L. Sorenson, (2008) Beneficial Effects of Lipids and Prolactin on Insulin Secretion and Beta Cell Proliferation: A Role of Lipids in the Adaptation of Islets in Pregnancy. Journal of Endocrinoloyg 197: 265-276
A.J. Weinhaus, L.E. Stout, N.V. Bhagroo, T. Clark Brelje, R.L. Sorenson, (2007) Regulation of Islet Glucokinase in Pancreatic Islets by Prolactin: A Mechanism for Increasing Glucose-Stimulated Insulin Secretion during Pregnancy. Journal of Endocrinology 193:367-381.
R.L. Sorenson, L.E. Stout, T.C. Brelje, T.L. Jetton and F.M. Matschinsky 2007 Immunohistochemical Evidence for the Presence of Glucokinase in the Gonadotropes and Thyrotropes of the Anterior Pituitary Gland of Rat and Monkey. Journal Histochemistry and Cytochemistry 55:555-566.
R.L. Sorenson, D.G. Garry and T.C. Brelje, (2006) Structural and Functional Considerations of GABA in Islets of Langerhans: Beta-cells and Nerves A Retrospective. In Perspectives in Diabetes, Vol I, ed. R. Paul Robertson.
Sorenson RL, Weinhaus AJ, and Brelje TC (2004) Regulation of Glucokinase as Islets Adapt to Pregnancy in Glucose and Glycemic Diseases: from Basics to Novel Therapeutics (F Matschinsky and M Magnuson eds.) S Karger AG Basel
Brelje TC, Stout LE, Bhagroo NV, and Sorenson RL (2004) Distinctive Roles for Prolactin and Growth hormone in the Acivation of STAT5 in Pancreatic Islets of Langerhans. Endocrinology 145:4162-4175.
Brelje, TC, Svensson AM, Stout LE, Bhagroo NV and Sorenson RL 2002 An Immunohistochemical approach to monitor the prolactin-induced activation of the JAK/Stat5 pathway in pancreatic islets of Langerhans. Journal Histochemistry and Cytochemistry 50:365-383.
Sorenson, R.L., and Brelje, T.C. 2001 Differences in the regulation of pancreatic islets by prolactin, growth hormone and placental lactogen. In Prolactin (ed. Nelson Horseman) Kluwer, Boston. 297-316.