Ultrastructural islet study of early fibrosis in the Ren2 rat model of hypertension. Emerging role of the islet pancreatic pericyte-stellate cell.
BACKGROUND
Type 2 diabetes mellitus is a multifactorial disease with polygenic and environmental stressors resulting in multiple metabolic toxicities and islet oxidative stress. We have integrated the role of the islet renin-angiotensin system (RAS) in the pathogenesis of early islet fibrosis utilizing the transgenic (mRen2)27 rodent model of hypertension and tissue RAS overexpression.


OBJECTIVE
The Ren2 pancreatic islet tissue was evaluated with transmission electron microscopy to study both early cellular and extracellular matrix remodeling.


METHODS
Four 9- to 10-week-old male Ren2 untreated models and four Sprague Dawley sex and age matched controls were used.


METHODS
Ultrastructural study to compare pancreatic islet tissue.


METHODS
Only qualitative and observational transmission electron microscopy findings are reported.


RESULTS
Major remodeling differences in the Ren2 model were found to be located within the islet exocrine interface, including deposition of early fibrillar-banded collagen (fibrosis) and cellular remodeling of the pericyte suggesting proliferation, migration, hypertrophy and activation as compared to the Sprague Dawley controls.


CONCLUSIONS
This study points to the possibility of the pericyte cell being one of many contributors to the fibrogenic pool of cells important for peri-islet fibrosis as a result of excess angiotensin II at the local tissue level in the Ren2 model. These findings suggest that the pericyte may be capable of differentiating into the pancreatic stellate cell. This islet ultrastructure study supports the notion that pericyte cells could be the link between islet vascular oxidative stress and peri-islet fibrosis. Pericyte-endothelial-pancreatic stellate cell associations and morphology are discussed.
Hayden
Melvin R
MR
Department of Internal Medicine, University of Missouri School of Medicine, D109 HSC Diabetes Center, Columbia, MO 65212, USA. mrh29@usmo.com
Karuparthi
Poorna R
PR
Habibi
Javad
J
Wasekar
Chetan
C
Lastra
Guido
G
Manrique
Camilla
C
Stas
Sameer
S
Sowers
James R
JR
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001786:Blood Glucose / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D005355:Fibrosis; D006973:Hypertension / Q000473:pathology* / Q000503:physiopathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D020286:Pericytes / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*
D001786:Blood Glucose; D000804:Angiotensin II