Ultrastructure of islet microcirculation, pericytes and the islet exocrine interface in the HIP rat model of diabetes.
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.
Hayden
Melvin R
MR
Department of Internal Medicine, University of Missouri School of Medicine, Columbia, Missouri 65212, USA. mrh29@usmo.com
Karuparthi
Poorna R
PR
Habibi
Javad
J
Lastra
Guido
G
Patel
Kamlesh
K
Wasekar
Chetan
C
Manrique
Camila Margarita
CM
Ozerdem
Ugur
U
Stas
Sameer
S
Sowers
James R
JR
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
D000199:Actins; D000682:Amyloid; D000906:Antibodies; D001786:Blood Glucose; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor