Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss.

Autor:	Richardson TM; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States., Saunders DC; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Haliyur R; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States., Shrestha S; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.; Creative Data Solutions, Vanderbilt Center for Stem Cell Biology, Nashville, Tennessee, United States., Cartailler JP; Creative Data Solutions, Vanderbilt Center for Stem Cell Biology, Nashville, Tennessee, United States., Reinert RB; Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, Michigan, United States.; Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, United States., Petronglo J; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Bottino R; Imagine Pharma, Pittsburgh, Pennsylvania, United States., Aramandla R; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Bradley AM; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Jenkins R; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Phillips S; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Kang H; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, United States., Caicedo A; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States.; Program of Neuroscience, University of Miami Miller School of Medicine, Miami, Florida, United States.; Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida, United States., Powers AC; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States.; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.; Department of Veterans Affairs Tennessee Valley Healthcare, Nashville, Tennessee, United States., Brissova M; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2023 Mar 01; Vol. 324 (3), pp. E251-E267. Date of Electronic Publication: 2023 Jan 25.
DOI:	10.1152/ajpendo.00246.2022
Abstrakt:	The autonomic nervous system regulates pancreatic function. Islet capillaries are essential for the extension of axonal projections into islets, and both of these structures are important for appropriate islet hormone secretion. Because beta cells provide important paracrine cues for islet glucagon secretion and neurovascular development, we postulated that beta cell loss in type 1 diabetes (T1D) would lead to a decline in intraislet capillaries and reduction of islet innervation, possibly contributing to abnormal glucagon secretion. To define morphological characteristics of capillaries and nerve fibers in islets and acinar tissue compartments, we analyzed neurovascular assembly across the largest cohort of T1D and normal individuals studied thus far. Because innervation has been studied extensively in rodent models of T1D, we also compared the neurovascular architecture between mouse and human pancreas and assembled transcriptomic profiles of molecules guiding islet angiogenesis and neuronal development. We found striking interspecies differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting that posttranscriptional regulation may be involved in this process. To determine whether islet neurovascular arrangement is altered after beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10-yr duration), and longstanding T1D (>10-yr duration) donors. Recent-onset T1D showed greater islet and acinar capillary density compared to non-diabetic and longstanding T1D donors. Both recent-onset and longstanding T1D had greater islet nerve fiber density compared to non-diabetic donors. We did not detect changes in sympathetic axons in either T1D cohort. Additionally, nerve fibers overlapped with extracellular matrix (ECM), supporting its role in the formation and function of axonal processes. These results indicate that pancreatic capillaries and nerve fibers persist in T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components. NEW & NOTEWORTHY Defining the neurovascular architecture in the pancreas of individuals with type 1 diabetes (T1D) is crucial to understanding the mechanisms of dysregulated glucagon secretion. In the largest T1D cohort of biobanked tissues analyzed to date, we found that pancreatic capillaries and nerve fibers persist in human T1D despite beta cell loss, suggesting that alpha cell secretory changes may be decoupled from neurovascular components. Because innervation has been studied extensively in rodent T1D models, our studies also provide the first rigorous direct comparisons of neurovascular assembly in mouse and human, indicating dramatic interspecies differences.
Databáze:	MEDLINE
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