Glucose-dependent blood flow dynamics in murine pancreatic islets in vivo
Year: 2010
Type: article
Abstract: Pancreatic islets are highly vascularized and arranged so that regions containing beta-cells are distinct from those containing other cell types. Although islet blood flow has been studied extensively, little is known about the dynamics of islet blood flow during hypoglycemia or hyperglycemia. To investigate changes in islet blood flow as a function of blood glucose level, we clamped blood glucose sequentially at hyperglycemic ( approximately 300 mg/dl or 16.8 mM) and hypoglycemic ( approximately 50 mg/dl or 2.8 mM) levels while simultaneously imaging intraislet blood flow in mouse models that express green fluorescent protein in the beta-cells or yellow fluorescent protein in the alpha-cells. Using line scanning confocal microscopy, in vivo blood flow was assayed after intravenous injection of fluorescent dextran or sulforhodamine-labeled red blood cells. Regardless of the sequence of hypoglycemia and hyperglycemia, islet blood flow is faster during hyperglycemia, and apparent blood volume is greater during hyperglycemia than during hypoglycemia. However, there is no change in the order of perfusion of different islet endocrine cell types in hypoglycemia compared with hyperglycemia, with the islet core of beta-cells usually perfused first. In contrast to the results in islets, there was no significant difference in flow rate in the exocrine pancreas during hyperglycemia compared with hypoglycemia. These results indicate that glucose differentially regulates blood flow in the pancreatic islet vasculature independently of blood flow in the rest of the pancreas.
Institutions: Vanderbilt University, VA Tennessee Valley Healthcare System
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Veterans Affairs, Vanderbilt University, National Eye Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Eunice Kennedy Shriver Intellectual and Developmental Disability Research Center, Pancreatic Islet Imaging and Blood Flow, Molecular Mechanisms of Human and Murine Beta Cell Proliferation and Regeneration, G2906896244, G2940777275, G33365108, G3989539122, Vanderbilt Mouse Metabolic Phenotyping Center, Molecular Determinants of Vascularization in Islets, Diabetes Research and Training Center, Dynamics of Pancreatic Islet Function, LSM 5 Live Microscope for Cell Imaging Shared Resource, VEGF and Islet Vascularization, G6845279160, GLP-1 to Enhance Islet Transplantation, Multidisciplinary Training in Molecular Endocrinology, Molecular and Cellular Basis for Digestive Diseases, Cancer Center Support Grant, Vanderbilt Diabetes Research Center, Core Grant in Vision Research
OpenAlex ID: W2020142860