title: [11C]5-hydroxy-tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes.
abstract: [11C]5-hydroxy-tryptophan ([11C]5-HTP) positron emission tomography of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by noninvasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to individuals without diabetes. The primary outcome was the [11C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass. We found that metabolic testing indicated a progressive loss of β-cell function, but this was not mirrored by a decrease in [11C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased β-cell function. The results herein indicate that β-cell dedifferentiation, and not necessarily endocrine cell loss, constitutes a major cause of β-cell failure in T2D.
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Carlbom
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Espes
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Martinell
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.|Antaros Medical AB, Mölndal, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Ahlström
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Per-Ola
authors.initials: PO
authors.lastname: Carlsson
authors.affiliation: Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.affiliation: Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden olof.eriksson@pet.medchem.uu.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
mesh_terms: D006916:5-Hydroxytryptophan; D000368:Aged; D001120:Arginine; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002454:Cell Differentiation; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005947:Glucose; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D007515:Islets of Langerhans / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D000072078:Positron Emission Tomography Computed Tomography
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D002250:Carbon Radioisotopes; D007004:Hypoglycemic Agents; D007328:Insulin; D001120:Arginine; D006916:5-Hydroxytryptophan; D005947:Glucose