Pancreatic polypeptide (PP) and peptide YY (PYY) are members of a brain-gut peptide family. Pancreatic polypeptide, produced in the pancreatic islets, inhibits pancreatic exocrine secretion and relaxes the gallbladder. Peptide YY, which is made in endocrine cells of the colon and ileum, also inhibits pancreatic exocrine secretion. Other effects of PYY include inhibition of intestinal motility, gastric emptying, and gastric secretion of pepsin as well as reduction of intestinal blood flow. The secretion of each peptide appears to be regulated by a number of nutritive and neural stimuli. Increased production of pancreatic polypeptide is frequently associated with pancreatic disease, in particular, with islet cell tumors of the pancreas and diabetes mellitus. Increased secretion of PYY has been observed in chronic diarrheal illnesses associated with malabsorption. Many of the unanswered questions about the biosynthesis and regulation of these two peptides can be addressed by recombinant DNA technology. To determine whether factors known to regulate the secretion of PP also regulate its biosynthesis, PP mRNA levels will be measured in pancreas from normal rats, diabetic rats, in primary cultures of islets, and in RIN cells, using northern blot assays. To accomplish these objectives the rat PP gene will be isolated and characterized from a genomic library. A PYY cDNA, which I have recently isolated from a bacteriophage lambda gt11 cDNA expression library prepared from rat intestine, will be used as a hybridization probe to determine the tissue localization and regulation of PYY biosynthesis. In addition the gene encoding PYY will be isolated from a genomic library. Finally, the tissue localization of PYY and PP and the fetal development of PP will be defined utilizing the technique of in situ hybridization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29DK039209-01
Application #
3463099
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1987-08-01
Project End
1991-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02111
Upchurch, B H; Aponte, G W; Leiter, A B (1994) Expression of peptide YY in all four islet cell types in the developing mouse pancreas suggests a common peptide YY-producing progenitor. Development 120:245-52
Krasinski, S D; Wheeler, M B; Leiter, A B (1991) Isolation, characterization, and developmental expression of the rat peptide-YY gene. Mol Endocrinol 5:433-40
Krasinski, S D; Wheeler, M B; Kopin, A S et al. (1990) Pancreatic polypeptide and peptide YY gene expression. Ann N Y Acad Sci 611:73-85
Kopin, A S; Toder, A E; Leiter, A B (1988) Different splice site utilization generates diversity between the rat and human pancreatic polypeptide precursors. Arch Biochem Biophys 267:742-8