The endocrine pancreas of alloxan-diabetic rats: microangiopathy as revealed by electron microscopy

Nakamura, Mitsuo; Hamaguchi, Kazuyuki; Ono, Junko; Takaki, Ryosaburo; Kitamura, Hirokazu; Nakamura, Harumi; Noguchi, Tsuyoshi; Ina, Keisuke

doi:10.1016/0168-8227(89)90002-8

Cited by 2 publications

(1 citation statement)

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“…However, alterations of vasculature exist in several type 2 diabetes animal models. The db/db mouse shows decreased capillary density and, increase in the mean and diversity of capillary size, associated with pericapillary oedema, fibrosis and irregularity of the endothelial luminal surface [15], [16]. Likewise spontaneously (nonobese) diabetic Goto-Kakizaki rats have deficient islet vascularization from neonatal life to adulthood [17].…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin 2 Alters Pancreatic Vascularization in Diabetic Conditions

et al. 2012

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Aims/hypothesisIslet vascularization, by controlling beta-cell mass expansion in response to increased insulin demand, is implicated in the progression to glucose intolerance and type 2 diabetes. We investigated how hyperglycaemia impairs expansion and differentiation of the growing pancreas. We have grafted xenogenic (avian) embryonic pancreas in severe combined immuno-deficient (SCID) mouse and analyzed endocrine and endothelial development in hyperglycaemic compared to normoglycaemic conditions.Methods14 dpi chicken pancreases were grafted under the kidney capsule of normoglycaemic or hyperglycaemic, streptozotocin-induced, SCID mice and analyzed two weeks later. Vascularization was analyzed both quantitatively and qualitatively using either in situ hybridization with both mouse- and chick-specific RNA probes for VEGFR2 or immunohistochemistry with an antibody to nestin, a marker of endothelial cells that is specific for murine cells. To inhibit angiopoietin 2 (Ang2), SCID mice were treated with 4 mg/kg IP L1–10 twice/week.ResultsIn normoglycaemic condition, chicken-derived endocrine and exocrine cells developed well and intragraft vessels were lined with mouse endothelial cells. When pancreases were grafted in hyperglycaemic mice, growth and differentiation of the graft were altered and we observed endothelial discontinuities, large blood-filled spaces. Vessel density was decreased. These major vascular anomalies were associated with strong over-expression of chick-Ang2. To explore the possibility that Ang2 over-expression could be a key step in vascular disorganization induced by hyperglycaemia, we treated mice with L1–10, an Ang-2 specific inhibitor. Inhibition of Ang2 improved vascularization and beta-cell density.ConclusionsThis work highlighted an important role of Ang2 in pancreatic vascular defects induced by hyperglycaemia.

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Section: Introductionmentioning

confidence: 99%