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

Exp Biol Med (Maywood). 2008 Sep;233(9):1109-23. doi: 10.3181/0709-RM-251. Epub 2008 Jul 18.

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- 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.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Aging / physiology
  • Amyloid / metabolism*
  • Animals
  • Antibodies / immunology
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology*
  • Disease Models, Animal
  • Humans
  • Male
  • Microcirculation
  • Microscopy, Electron, Transmission
  • Muscle, Smooth / metabolism
  • Pancreas, Exocrine / ultrastructure*
  • Pancreatic Diseases / pathology*
  • Peptides / metabolism*
  • Pericytes / ultrastructure*
  • Platelet-Derived Growth Factor / immunology
  • Platelet-Derived Growth Factor / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Platelet-Derived Growth Factor / metabolism

Substances

  • Actins
  • Amyloid
  • Antibodies
  • Blood Glucose
  • Peptides
  • Platelet-Derived Growth Factor
  • Receptors, Platelet-Derived Growth Factor