Biology Reference
In-Depth Information
Table 12.1
Features of islet endothelial cells compared to those in exocrine pancreas. See text for
details
Exposed to high blood flow
[9, 45]
High production of and sensitivity to endothelium-derived relaxing and
constricting factors; e.g. nitric oxide and endothelin-1
[52, 80]
Different types of surface receptors
[72]
Different production of pro-angiogenic and angiostatic peptides;
e.g. VEGF-A and thrombospondin-1, basic fibroblast growth factor
[55, 59, 70]
β
Regulates
-cell proliferation by growth factors and provides a niche for
[48, 50]
β
-cell growth
Transgenic animals with impaired glucose tolerance often show altered
capillary morphology
[2, 55]
Both the islet vasculature and blood flow are affected in animal models of type
2 diabetes. It has been suggested that islet vascular defects, including impaired
signaling between
- and islet endothelial cells, adversely affect the endocrine
function in human diabetes [45, 53]. The adaptor protein Shb is associated with
and relays signals from VEGF-activated VEGFR2. The resulting stimulation of
the PI3-kinase with activation of FAK in concert with Src promote cytoskeletal
rearrangements [41].
β
12.3.5 Blood Flow Direction in the Islets
Despite species differences most islets are usually supplied with arterioles separate
from those to the exocrine pancreas (Fig. 12.1). Each islet receives 1-3 arterioles,
which branch into fenestrated capillaries. An important issue is how the arterioles
enter the islets. A summary of this debate has been provided [9]. Briefly, it was
claimed that the arterioles enter through discontinuities in the islet periphery lacking
β
-cells and branch into capillaries. This has led to the hypothesis that the arterial
blood first reaches
β
-cells, in the core of the islets providing high concentrations of
insulin to
-cells.
Accordingly, there is a preferential flow direction through the islets important for
paracrine interactions between islet cells [78]. However, other morphological data
indicate that the arterioles branch into capillaries before the entry into the islets [9].
A third theory is that the cellular order of blood perfusion varies between the species,
depending upon islet cytoarchitecture [9, 33]. We recently developed a technique to
perfuse large single rodent islets (Fig. 12.2), and found that the branching occurs
outside the islets. However, it cannot be excluded that arterioles in some large islets
can enter the central parts of the islets [69].
The absence of arterioles within the islets would exclude the possibility of
islet blood flow regulation by direct actions of islet metabolites and/or hormones
on VSM in the blood vessel wall. It is possible that endocrine cell metabolism,
which is known to affect islet blood flow [17], must affect the endothelial cells,
which then retrogradely informs the arterioles about the need for vasoconstriction or
α
- and
δ
-cells. Glucagon from
α
-cells mainly affects the adjacent
δ
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