title: An optical method to evaluate both mass and functional competence of pancreatic α- and β-cells.
abstract: Imbalanced glucagon and insulin release leads to the onset of type 2 diabetes. To pinpoint the underlying primary driving force, here we have developed a fast, non-biased optical method to measure ratios of pancreatic α- and β-cell mass and function simultaneously. We firstly label both primary α- and β-cells with the red fluorescent probe ZinRhodaLactam-1 (ZRL1), and then highlight α-cells by selectively quenching the ZRL1 signal from β-cells. Based on the signals before and after quenching, we calculate the ratio of the α-cell to β-cell mass within live islets, which we found matched the results from immunohistochemistry. From the same islets, glucagon and insulin release capability can be concomitantly measured. Thus, we were able to measure the ratio of α-cell to β-cell mass and their function in wild-type and diabetic Lepr(db)/Lepr(db) (denoted db/db) mice at different ages. We find that the initial glucose intolerance that appears in 10-week-old db/db mice is associated with further expansion of α-cell mass prior to deterioration in functional β-cell mass. Our method is extendable to studies of islet mass and function in other type 2 diabetes animal models, which shall benefit mechanistic studies of imbalanced hormone secretion during type 2 diabetes progression.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Yi
authors.identifier: 0000-0001-7956-3102
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Chengsheng
authors.initials: C
authors.lastname: Han
authors.affiliation: State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China.
authors.forename: Wenzhen
authors.initials: W
authors.lastname: Zhu
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China lychen@pku.edu.cn yanmeiliu@pku.edu.cn.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Membrane Biology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking University, Beijing 100871, China lychen@pku.edu.cn yanmeiliu@pku.edu.cn.
authors.forename: Liangyi
authors.identifier: 0000-0003-1270-7321
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology; D018450:Disease Progression; D005021:Ethylamines / Q000494:pharmacology; D005453:Fluorescence; D050416:Glucagon-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D055095:Optics and Photonics / Q000379:methods*; D009929:Organ Size / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D013194:Staining and Labeling
chemical_list: D005021:Ethylamines; C511824:N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; D011725:Pyridines
keywords: Diabetes; Glucagon secretion; Insulin secretion; Islets; α-cell mass; β-cell mass