American Diabetes Association
Browse
DOCUMENT
Tamayo_et_al_Supplementary_Material_Diabetes_R1-1.pdf (5.35 MB)
DOCUMENT
Human_Islet_Checklist_Diabetes.pdf (81.09 kB)
VIDEO
Movie_S2.avi (2.39 MB)
VIDEO
Movie_S1.avi (37.83 MB)
VIDEO
Movie_S3.avi (34.07 MB)
VIDEO
Movie_S4.avi (11.6 MB)
1/0
6 files

Pericyte control of blood flow in intraocular islet grafts impacts glucose homeostasis in mice

figure
posted on 2022-05-19, 12:29 authored by Alejandro Tamayo, Luciana Gonçalves, Rayner Rodriguez-Diaz, Elizabeth Pereira, Melissa Canales, Alejandro Caicedo, Joana Almaça

  

The pancreatic islet depends on blood supply to efficiently sense plasma glucose levels and deliver insulin and glucagon into the circulation. Long thought to be passive conduits of nutrients and hormones, islet capillaries were recently found to be densely covered with contractile pericytes with the capacity to locally control blood flow. Here we determined the contribution of pericyte regulation of islet blood flow to plasma insulin and glucagon levels and glycemia. Selective optogenetic activation of pericytes in intraocular islet grafts contracted capillaries and diminished blood flow. In awake mice, acute light-induced stimulation of islet pericytes decreased insulin and increased glucagon plasma levels, producing hyperglycemic effects. Interestingly, pericytes are the targets of sympathetic nerves in the islet, suggesting that sympathetic control of hormone secretion may occur in part by modulating pericyte activity and blood flow. Indeed, in vivo activation of pericytes with the sympathetic agonist phenylephrine decreased blood flow in mouse islet grafts, lowered plasma insulin levels and increased glycemia. We further show that islet pericytes and blood vessels in living human pancreas slices responded to sympathetic input. Our findings indicate that pericytes mediate vascular responses in the islet that are required for adequate hormone secretion and glucose homeostasis. Vascular and neuronal alterations that are commonly seen in the islets of people with diabetes may impair regulation of islet blood flow and thus precipitate islet dysfunction.

Funding

This work was funded by NIH grants [K01DK111757 (J.A.), R01DK08432, R01DK111538, R01DK113093 (A.C.) and by the NIDDK-supported Human Islet Research Network (HIRN, RRID:SCR_014393; https://hirnetwork.org; UC4 DK104162, New Investigator Pilot Award to J.A.).

History

Usage metrics

    Diabetes

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC