title: Human islet preparations distributed for research exhibit a variety of insulin-secretory profiles.
abstract: Human islet research is providing new insights into human islet biology and diabetes, using islets isolated at multiple US centers from donors with varying characteristics. This creates challenges for understanding, interpreting, and integrating research findings from the many laboratories that use these islets. In what is, to our knowledge, the first standardized assessment of human islet preparations from multiple isolation centers, we measured insulin secretion from 202 preparations isolated at 15 centers over 11 years and noted five distinct patterns of insulin secretion. Approximately three quarters were appropriately responsive to stimuli, but one quarter were dysfunctional, with unstable basal insulin secretion and/or an impairment in stimulated insulin secretion. Importantly, the patterns of insulin secretion by responsive human islet preparations (stable Baseline and Fold stimulation of insulin secretion) isolated at different centers were similar and improved slightly over the years studied. When all preparations studied were considered, basal and stimulated insulin secretion did not correlate with isolation center, biological differences of the islet donor, or differences in isolation, such as Cold Ischemia Time. Dysfunctional islet preparations could not be predicted from the information provided by the isolation center and had altered expression of genes encoding components of the glucose-sensing pathway, but not of insulin production or cell death. These results indicate that insulin secretion by most preparations from multiple centers is similar but that in vitro responsiveness of human islets cannot be predicted, necessitating preexperimental human islet assessment. These results should be considered when one is designing, interpreting, and integrating experiments using human islets.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Nora S
authors: NS
authors: Kayton
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Gregory
authors: G
authors: Poffenberger
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Joseph
authors: J
authors: Henske
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Chunhua
authors: C
authors: Dai
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Courtney
authors: C
authors: Thompson
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Radhika
authors: R
authors: Aramandla
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Alena
authors: A
authors: Shostak
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Wendell
authors: W
authors: Nicholson
authors: Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee;
authors: Marcela
authors: M
authors: Brissova
authors: Center for Human Genetics Research, Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee; and.
authors: William S
authors: WS
authors: Bush
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; Veterans Affairs Tennessee Valley Healthcare System, Nashville, Tennessee al.powers@vanderbilt.edu.
authors: Alvin C
authors: AC
authors: Powers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012106:Research; D013048:Specimen Handling; D014019:Tissue Donors / Q000706:statistics & numerical data / Q000600:supply & distribution; D009927:Tissue and Organ Procurement / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: D007328:Insulin
keywords: function; human; islet
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