Pancreatic Islet Blood Flow Dynamics in Primates Diez, Juan A. et al. Cell Reports, Volume 20, Issue 6, 1490 - 1501
Blood flow regulation in pancreatic islets is critical for function but poorly understood. Here, we establish an in vivo imaging platform in a non-human primate where islets transplanted autologously into the anterior chamber of the eye are monitored non-invasively and longitudinally at single-cell resolution. Engrafted islets were vascularized and innervated and maintained the cytoarchitecture of in situ islets in the pancreas. Blood flow velocity in the engrafted islets was not affected by increasing blood glucose levels and/or the GLP-1R agonist liraglutide. However, islet blood flow was dynamic in nature and fluctuated in various capillaries. This was associated with vasoconstriction events resembling a sphincter-like action, most likely regulated by adrenergic signaling. These observations suggest a mechanism in primate islets that diverts blood flow to cell regions with higher metabolic demand. The described imaging technology applied in non-human primate islets may contribute to a better understanding of human islet pathophysiology.
We thank Bryan Ogden and the veterinary team at SEMC, SingHealth, for technical support with animal care and handling. This work was supported by a Lee Kong Chian School of Medicine, Nanyang Technological University start-up grant (to P.O.B.) M4230003 , the Swedish Research Council , the Family Erling-Persson Foundation , the Novo Nordisk Foundation , the Stichting af Jochnick Foundation , the Swedish Diabetes Association , the Scandia Insurance Company , the Diabetes Research and Wellness Foundation , Berth von Kantzow’s Foundation , the Strategic Research Program in Diabetes at Karolinska Institutet , the ERC ERC-2013-AdG 338936-Betalmage , and the Knut and Alice Wallenberg Foundation . R.A.D. was supported by the Nanyang Structural Biology Institute ( NISB ) L0408020 and by an AXA Research Fund post-doctoral fellowship, L0484201 . V.A.B. is supported by National Medical Research Council, Singapore grant NMRC/CG/015/2013 . P.O.B. is co-founder and CEO of Biocrine, an unlisted biotech company that is using the ACE technique as a research tool