The long-term goal is to further clarify the basis of pancreative circulation in a murine copper-deficient model and to determine its applicability to the study of normal pancreatic vasculature. Although there are proposed models of pancreatic blood flow, these are not without significant discrepancy. Some models suggest a parallel flow of blood to and from endocrine islets independent and exclusive of acinar circulation. Other models suggest a serial circulation in which all the blood of the pancreas flows initially to the islets and subsequently to acinar capillaries before exiting from the organ. Since our understanding of the functional relationship between endocrine and exocrine pancreas has significant physiological implications related to the stimulatory and/or inhibitory effects of islet hormones on the exocrine gland, a clearer knowledge of the intimate circulatory relationship between islets and acini is essential.
The specific aim of this project will be to undertake a study of the progressive pancreatic vascular changes in dietary induced copper deficiency. This metal-deficient state is proposed as an alternate model for the study of pancreatic circulation because it effects highly selective atrophic changes in acinar tissue which eliminates acinar portal drainage without altering the efferent flow from endocrine islets based on preliminary studies. While this tentatively lends considerable support to an independent or parallel model of microcirculation, a systematic investigation is necessary to further characterize vasculature during the developmental phases of Cu deficiency. Furthermore, the effects of regeneration of the gland on microcirculation in the reversed state of copper deficiency will be studied as well. The proposed characterization of these changes will be based on a scanning electron microscopic (SEM) analysis of pancreatic corrosion casts prepared from copper-deficient rats during the developmental and regressive phases of this metal-deficient state. In order to compare the static vascular architecture obtained from SEM casts to the dynamics of flow, in vivo study of injected Evans blue and microspheres will be used as supplemental tools of analysis. These techniques will be applied in this proposed study to obtain crucial information required to assess the circulatory transport of islet hormones under the conditions of copper-deficient induced acinar atrophy which is presently not available. The further characterization of this potential model may contribute significant information to our understanding of normal pancreatic microcirculation and exo-endocrine correlates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK036745-02
Application #
3235248
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
St. John's University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Collegeville
State
MN
Country
United States
Zip Code
56321