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First published online July 18, 2008
Experimental Biology and Medicine doi: 10.3181/0709-RM-251
© 2008 by the Society for Experimental Biology and Medicine
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Regular Manuscript

Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes

Melvin R Hayden 1*, Poorna R Karuparthi 1, Javad Habibi 1, Guido Lastra G Lastra 1, Kamlesh Patel 1, Chetan Wasekar 2, Camila M Manrique 2, Ugur Ozerdem 3, Sameer Stas 2, and James R Sowers 1

1 University of Missouri
2 University of Missouri School of Medicine
3 La Jolla Institute for Molecular Medicine

* To whom correspondence should be addressed. E-mail: mrh29{at}usmo.com.


  Abstract

Context: The transgenic human islet amyloid polypeptide (HIP) rat model of type 2 diabetes mellitus (T2DM) parallels the functional and structural changes in human islets with T2DM. Objective The transmission electron microscope (TEM) was utilized to observe the ultrastructural changes in islet microcirculation. Methods Pancreatic tissue from male Sprague Dawley rats (2, 4, 8, 14 months) were used as controls (SDC) and compared to the 2, 4, 8 and 14 month old HIP rat models. Results The 2 month old HIP model demonstrated no islet or microcirculation remodeling changes when compared to the SDC models. The 4 month old HIP model demonstrated significant pericapillary amyloid deposition and diminution of pericyte foot processes as compared to the SDC models. The 8 month old model demonstrated extensive islet amyloid deposition associated with pericyte and {beta}-cell apoptosis when compared with SDC. The 14 month old HIP model demonstrated a marked reduction of {beta}-cells and intra-islet capillaries with near complete replacement of islets by amyloidoses. Increased cellularity in the region of the islet exocrine interface was noted in the 4-14 month old HIP models as compared to SDC. In contrast to intra-islet capillary rarefaction there was noticeable angiogenesis in the islet exocrine interface. Pericytes seemed to be closely associated with collagenosis, intra-islet adipogenesis and angiogenesis in the islet exocrine interface. Conclusion The above novel findings regarding the microcirculation and pericytes could assist researchers and clinicians in a better morphological understanding of T2DM and lead to new strategies for prevention and treatment of T2DM.

Key Words: Amylin, angiogensis, apoptosis, beta cell, islet amyloid, islet fibrosis






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Copyright © 2008 by the Society for Experimental Biology and Medicine.