Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes

Drotar, D.; Mojica-Avila, A. K.; Bloss, D. T.; Cohrs, C. M.; Manson, C. T.; Posgai, A. L.; Williams, M. D.; Brusko, M. A.; Phelps, E. A.; Wasserfall, C. H.; Speier, S.; Atkinson, M. A.

doi:10.1101/2024.02.08.579175

bioRxiv · 10.1101/2024.02.08.579175

Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes

Drotar, D.·Mojica-Avila, A. K.·Bloss, D. T.·Cohrs, C. M.·Manson, C. T.·Posgai, A. L.·Williams, M. D.·Brusko, M. A.·Phelps, E. A.·Wasserfall, C. H.·Speier, S.·Atkinson, M. A.

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Abstract

Histopathological heterogeneity in human pancreas has been well documented; however, functional evidence at the tissue level is scarce. Herein we investigated in situ glucose-stimulated islet and carbachol-stimulated acinar cell secretion across the pancreas head (PH), body (PB), and tail (PT) regions in no diabetes (ND, n=15), single islet autoantibody-positive (1AAb+, n=7), and type 1 diabetes donors (T1D, <14 months duration, n=5). Insulin, glucagon, pancreatic amylase, lipase, and trypsinogen secretion along with 3D tissue morphometrical features were comparable across the regions in ND. In T1D, insulin secretion and beta-cell volume were significantly reduced within all regions, while glucagon and enzymes were unaltered. Beta-cell volume was lower despite normal insulin secretion in 1AAb+, resulting in increased volume-adjusted insulin secretion versus ND. Islet and acinar cell secretion in 1AAb+ were consistent across PH, PB and PT. This study supports low inter-regional variation in pancreas slice function and potentially, increased metabolic demand in 1AAb+.

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Drotar, D., Mojica-Avila, A. K., Bloss, D. T., Cohrs, C. M., Manson, C. T., Posgai, A. L., Williams, M. D., Brusko, M. A., Phelps, E. A., Wasserfall, C. H., Speier, S., Atkinson, M. A.. 2024-02-12. Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes. https://doi.org/10.1101/2024.02.08.579175

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