Geoffrey Sharp

<TITLE>Geoffrey Sharp</TITLE> <CENTER><TABLE BORDER=0 ALIGN=CENTER VALIGN=TOP CELLPADDING=10> <TR> <TD VALIGN=TOP><table border=3 cellpadding=1><tr><td><IMG Align=TOP SRC="sharp_picture1.jpeg" height=100 width=110 ></td></tr></table></TD> <TD VALIGN=MIDDLE><B><H2><CENTER>Geoffrey W.G. Sharp</CENTER></H2><HR> <H3>Professor of Pharmacology<BR> <A HREF="../MolecMed.html">Department of Molecular Medicine</A><BR> College of Veterinary Medicine<BR> Cornell University</H3></TD> </TR> </TABLE> </CENTER> <HR> <BR> <Strong>Diabetes and Transepithelial Transport</Strong> <P> (1) A variety of physiologic, pharmacologic, biochemical and electrophysiological techniques are in use to explore the regulation of beta-cell function. These include the perifusion of pancreatic islets and radioimmunoassay, to measure the minute by minute release of insulin under basal, stimulated or inhibited conditions; the use of fluorescent dyes to measure the concentration of intracellular Ca++ and other second messengers in stimulus-secretion coupling; biochemical techniques for enzyme assays or intracellular substrate determination; and the use of clonal b-cell lines. <P>Major emphasis is currently placed on understanding the mechanisms of action of inhibitors of insulin secretion such as alpha2-adrenergic agonists, somatostatin, prostaglandins and galanin. These agents exert a variety of effects - all sensitive to pertussis toxin - to suppress insulin secretion. Among these are activation of KATP channels to hyperpolarize the cell membrane, inhibition of the L-type voltage-dependent Ca2+-channels to block Ca2+ entry, inhibition of adenylyl cyclase and an as yet unknown "distal" effect late in stimulus-secretion coupling, perhaps at a site involved with the final stages of exocytosis. <P> (2) Again, physiologic, pharmacologic and biochemical techniques are being brought to bear on the mechanisms controlling electrolyte transport in the small intestine, using tissues and cells from rabbits, pigs, rats and clonal cell lines of transporting cells. For the measurement of ion transport across the intestine or cell layers cultured on millipore filters, the short circuit current technique with radioisotopic flux measurements is in use. Assays for enzyme activities and intracellular concentrations of potential transport control substrates are performed under conditions in which transport is being simultaneously monitored. One area of current emphasis includes the characterization of the second messenger systems involved in the action of serotonin to stimulate Cl- secretion. Two distinct receptors for serotonin have been detected which increase Cl- secretion. One is HT4-like and positively coupled to adenylyl cyclase. The second messenger used by the other receptor is currently unknown. <P> <A HREF = "Sharp_CV.html">Curriculum vitae and selected publications</A><BR><P> <HR WIDTH="75%"><P> <BR> <CENTER><A HREF = "../cornell_pharmacology.html">Field of Pharmacology Home Page</A></CENTER> <BR> <HR> <BR> <TABLE BORDER=0 ALIGN=LEFT VALIGN=TOP CELLPADDING=5> <TR> <TD VALIGN=TOP><IMG Align=Top SRC="../faculty_pictures/sharp_low.jpeg"></A></TD> <TD VALIGN=MIDDLE> <PRE>Geoffrey Sharp Department of Pharmacology College of Veterinary Medicine Cornell University Ithaca, New York 14853 USA <a href=mailto:Geoffrey_Sharp@cornell.edu>e-mail</a>: Geoffrey_Sharp@cornell.edu phone: 607-253-3650 FAX: 607-253-3659 </PRE> </TD> </TR> </TABLE>