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Human pancreatic capillaries and nerve fibers persist in type 1 diabetes despite beta cell loss.
American Journal of Physiology. Endocrinology and Metabolism 2023 January 26
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 intra-islet 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 inter-species differences in islet neurovascular assembly but relatively modest differences at transcriptome level, suggesting post-transcriptional regulation may be involved in this process. To determine if islet neurovascular arrangement is altered following beta cell loss in T1D, we compared pancreatic tissues from non-diabetic, recent-onset T1D (<10 years duration), and longstanding T1D donors (>10 years duration). Both islets and acinar tissue had greater capillary density in recent-onset T1D accompanied by overall greater islet nerve fiber density in recent-onset and longstanding T1D as visualized by a pan-neuronal marker. 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.
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