An observational study in GLUCOSE METABOLISM, DIABETES and PANCREATIC ISLETS, sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Recruiting at 1 site in Italy. Open to participants aged 18 Years to 69 Years. Per ClinicalTrials.gov, last updated 2024-05-23.
Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Observational
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.
128 studies on the registry are indexed under Exocrine Pancreatic Insufficiency; 27 are open to participants now.
This study's planned enrollment of 100 is below the median of 115 across 35 observational studies indexed under Exocrine Pancreatic Insufficiency.
Browse Exocrine Pancreatic Insufficiency studies →Fondazione Policlinico Universitario Agostino Gemelli IRCCS is the lead sponsor of 920 studies on the registry; 529 are open to participants now.
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Patients scheduled for elective pancreaticoduodenectomy for periampullary neoplasms will be enrolled in the study. Indications for surgery will be periampullary neoplasms, i.e.
tumors of the Vater's ampulla, distal CBD and periampullary duodenum. Patients with pancreatic cancer will be excluded from the study. The metabolic features of all patients will be assessed before and after surgery. The patients will visit the Division of Endocrinology for studies at least 1 week before surgery. Only patients with normal cardiopulmonary and kidney functions, as determined by medical history, physical examination, screening blood tests, electrocardiogram and urinalysis, and not on any antidiabetic medications will be enrolled for metabolic assessments before and after surgery. Each subject will undergo, on separate days, a hyperinsulinemic euglycemic clamp, a hyperglycemic clamp and a mixed meal test one week before and after a variable period of recovery from the surgical procedure.
Exclusion Criteria:
Change from baseline in metabolic status (normal glucose tolerance, impaired glucose tolerance, diabetes)
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).
Time frame: baseline, 1 month after surgery and 1year after surgery
Changes in incretin levels from baseline
Incretin levels (GLP1 and GIP) will be measured during mixed meal test.
Time frame: baseline, 1 months after surgery and 1 year after surgery
Change in insulin secretion from baseline
Insulin secretion will be measured by Hyperglicemic clamp.
Time frame: baseline, 1 month after surgery and 1 year after surgery
islet cell areas (beta, Alpha and delta cell positive area)
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.
Time frame: baseline
changes in beta cell function in the context of disease of exocrine pancreas
Insulin secretion will be measured by Hyperglicemic clamp and ogtt.
Time frame: baseline
changes in intraislet ncRNA in different metabolic status
ncRNA sequenting in plasma and pancreas samples
Time frame: baseline
change in gene expression analysis among different groups of baseline metabolic status
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.
Time frame: baseline
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Exocrine Pancreatic Insufficiency→
Fondazione Policlinico Universitario Agostino Gemelli IRCCS