title: Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes.
abstract: BACKGROUND
  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- to 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri 65212, USA. mrh29@usmo.com
authors.forename: Melvin R
authors.initials: MR
authors.lastname: Hayden
authors.forename: Poorna R
authors.initials: PR
authors.lastname: Karuparthi
authors.forename: Javad
authors.initials: J
authors.lastname: Habibi
authors.forename: Guido
authors.initials: G
authors.lastname: Lastra
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Patel
authors.forename: Chetan
authors.initials: C
authors.lastname: Wasekar
authors.forename: Camila Margarita
authors.initials: CM
authors.lastname: Manrique
authors.forename: Ugur
authors.initials: U
authors.lastname: Ozerdem
authors.forename: Sameer
authors.initials: S
authors.lastname: Stas
authors.forename: James R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000199:Actins / Q000378:metabolism; D000375:Aging / Q000502:physiology; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D008833:Microcirculation; D046529:Microscopy, Electron, Transmission; D009130:Muscle, Smooth / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000648:ultrastructure*; D010182:Pancreatic Diseases / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D020286:Pericytes / Q000648:ultrastructure*; D010982:Platelet-Derived Growth Factor / Q000276:immunology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism
chemical_list: D000199:Actins; D000682:Amyloid; D000906:Antibodies; D001786:Blood Glucose; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor