mation of transactivation surfaces, and the coupling 
to other transcription factors. The structure and pro- 
moter region of the CREB gene, the diversity of addi- 
tional CREB-like gene products in other tissues, and 
the structure and characteristics of the C/EBP-like 
proteins involved in the acute-phase response w^ill 
be investigated. Efforts will also be made to isolate 
the cDNAs encoding the upstream and downstream 
DNA-binding proteins that cooperatively enhance 
cAMP-mediated activation of transcription of the 
glucagon and somatostatin genes. 
Dr. Habener has also focused investigations on the 
cell-specific post-translational processing of pro- 
glucagon. Previously he determined the sequence 
of the rat glucagon gene and discovered that the 
gene encodes a prohormone that includes not only 
glucagon but two additional peptides related in 
structure to glucagon, the glucagon-like peptides. 
Marked differences in the pattern of post-transla- 
tional processing of glucagon were found in rat pan- 
creas and intestine. The intestine produces predomi- 
nantly glucagon-like peptides, and the pancreas 
produces glucagon. 
Having established that proglucagon encodes 
new glucagon-like peptides. Dr. Habener investi- 
gated the potential biologic activities of these pep- 
tides. Glucagon-like peptide-I (GLP-I) is a potent 
insulinotropic peptide. When studied in pancreatic 
islet cell lines, GLP-I(7-37) stimulates insulin gene 
transcription, cAMP formation, and insulin secre- 
tion at concentrations in the picomolar range. More- 
over, GLP-I(7-37) stimulates insulin release in the 
perfused rat pancreas at concentrations as low as 
10"'^ M. Dr. Habener has determined that the pan- 
creatic |8-cell receptor for GLP-I(7-37) is distinct 
from that of glucagon in hepatic cells and that the 
receptor on |8 cells undergoes rapid homologous de- 
sensitization in a ligand-concentration manner. Ef- 
forts (supported in part by the National Institutes of 
Health) are being made to clone the /3-cell receptor 
for GLP-I(7-37). Administration of the synthetic 
peptide to both nondiabetic and diabetic (type II) 
humans results in a marked increase of plasma insu- 
lin levels followed by a fall in blood glucose levels. 
Dr. Habener is testing the therapeutic properties of 
GLP-I in patients with type II (non-insulin- 
dependent) diabetes mellitus to determine whether 
the peptide can ameliorate the abnormal rise in 
blood sugar after meals and return fasting sugar lev- 
els toward normal levels. 
Dr. Habener is also Professor of Medicine at 
Harvard Medical School and Associate Physician 
at Massachusetts General Hospital, Boston. 
Books and Chapters of Books 
Habener, J.F. 1992. Genetic control of hormone 
formation. In Williams Textbook of Endocrinol- 
ogy (Wilson, J.D., and Foster, D.W., Eds.). Phila- 
delphia, PA: Saunders, pp 9-34. 
Habener, J.F., Fehmann, H.C., Knepel, W., and 
Miller, CP. 1991. Regulation of glucagon synthe- 
sis and gene expression. In Diabetes 1991: Pro- 
ceedings of the 14th International Diabetes Fed- 
eration Congress, Washington, DC, 23-28 fune 
1991 (Rifkin, H., Colwell, J.A., and Taylor, S.I., 
Eds.). Amsterdam: Excerpta Medica, pp 263- 
270. 
Articles 
Fehmann, H.C., and Habener, J.F. 1992. Galanin 
inhibits proinsulin gene expression stimulated by 
the insulinotropic hormone glucagon-like pep- 
tide-I(7-37) in mouse insulinoma /3TC- 1 cells. En- 
docrinology 130:2890-2896. 
Fehmann, H.C., and Habener, J.F. 1992. Insulino- 
tropic glucagon-like peptide-I(7-37)/(7-36) 
amide: a new incretin hormone. Trends Endo- 
crinol Metab 3:158-163. 
Fehmann, H.C., and Habener, J.F. 1992. Insulino- 
tropic hormone glucagon-like peptide-I(7-37) 
stimulation of proinsulin gene expression and 
proinsulin biosynthesis in insulinoma /3TC-1 
cells. Endocrinology 130:159-166. 
Nathan, D.M., Schreiber, E., Fogel, H., Mojsov, S., 
and Habener, J.F. 1992. Insulinotropic action of 
glucagonlike peptide-I-(7-37) in diabetic and 
nondiabetic subjects. Diabetes Care 15:270- 
276. 
Ron, D., Brasier, A.R., McGehee, R.E., Jr., and Ha- 
bener, J.F. 1 992. Tumor necrosis factor-induced 
reversal of adipocyte phenotype of 3T3-L1 cells is 
preceded by a loss of nuclear CCAAT/enhancer 
binding protein (C/EBP)./ C/m Invest 89:223- 
233. 
Ron, D., and Habener, J.F. 1992. CHOP, a novel 
developmentally regulated nuclear protein that 
dimerizes with transcription factors C/EBP and 
LAP and functions as a dominant-negative inhibi- 
tor of gene transcription. Genes Dev 6:459-455. 
Vallejo, M., Miller, CP., and Habener, J.F. 1992. 
Somatostatin gene transcription regulated by a bi- 
partite pancreatic islet D-cell-specific enhancer 
coupled synergetically to a cAMP response ele- 
ment. /5/o/ Chem 267:12868-12875. 
Vallejo, M., Penchuk, L., and Habener, J.F. 1992. 
Somatostatin gene upstream enhancer element ac- 
tivated by a protein complex consisting of CREB, 
CELL BIOLOGY AND REGULATION 69 
