Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
Study Details
Study Description
Brief Summary
Regeneration of mature cells that produce functional insulin represents a major focus of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes. The capacity to adapt in response to diverse physiological conditions during life and the consequent ability to cope for increased metabolic demands is a distinctive feature of the endocrine pancreas in the regulation of glucose homeostasis. Both beta and alpha cells are dynamically regulated to continually maintain a balance between proliferation, neogenesis, and apoptosis. In this proposal, the investigators will focus on exploring key mechanism(s) that potentially regulate islet cell plasticity in altered glucose metabolic states.
Investigators will explore in a unique cohort of individuals who undergo duodenal pancretectomy. Prior to their surgery will be performed in vivo studies (Hyperglycemic clamp, Euglycemic Hyperinsulinemic clamp and Mixed Meal Tests) to accurately assess glucose homeostasis parameters to classify each individual into metabolic phenotypes. Then exploit the opportunity to collect pancreas samples from these patients who will be evaluated again after surgery, the investigators will determine the ability of the remnant pancreas to compensate for the acute reduction in islet mass and perform correlations between ex vivo and in vivo parameters.
Specifically, the patients will be subjected to incretin secretion (mixed meal), metabolic status (OGTT), insulin secretion characteristics (first and second phase responses), β-cell insulin content evaluation (arginine bolus). Subsequently, pancreas samples will be evaluated for morphometry, and proteomics and gene expression analyses of islet cell samples obtain by laser capture will allow a detailed investigation of mechanisms that contribute to islet plasticity. The overall goal of this project is to investigate key mechanisms driving the ability of islet mass to adapt to diverse metabolic states. We aim to explore modifications in gene expression and proteomics and correlate them with specific metabolic phenotypes, in order to determine key regulators of islet morphology.
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Study Design
Outcome Measures
Primary Outcome Measures
- Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes) [baseline, 1 month after surgery and 1year after surgery]
Metabolic status will be determined with oral glucose tolerance test and patients will be classified according their metabolic status (after 1 month and 1 year after surgery).
Secondary Outcome Measures
- Changes in incretin levels from baseline [baseline, 1 months after surgery and 1 year after surgery]
Incretin levels (GLP1 and GIP) will be measured during mixed meal test.
- Change in insulin secretion from baseline [baseline, 1 month after surgery and 1 year after surgery]
Insulin secretion will be measured by Hyperglicemic clamp.
- islet cell areas (beta, Alpha and delta cell positive area) [baseline]
Pancreas section will be immunostained for insulin, glucagon and somatostatin and Each section will be analyzed separately by measuring total insulin, glucagon or somatostatin positive areas, as well as the total pancreas section area, using Image Pro Plus software version 4. 5.1 . The β, α or δ cell areas will be expressed as percentage of total pancreas section area.
Other Outcome Measures
- change in gene expression analysis among different groups of baseline metabolic status [baseline]
Extract of islet cells will be dissected from pancreatic sections by laser capture microdissection and then extracted RNA will be analyzed by real time PCR analysis.
Eligibility Criteria
Criteria
Inclusion Criteria:
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SCHEDULED FOR ELECTIVE DUODENALPANCREATECTOMY
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NO DIABETIC
Exclusion Criteria:
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DIABETES
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CHRONIC DESEASES
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STEROID THERAPY
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PANCREATITIS
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PANCREATIC CANCER
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Endocrinology - Catholic University | Rome | RM | Italy | 00168 |
Sponsors and Collaborators
- Catholic University of the Sacred Heart
- Joslin Diabetes Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 14081985