Title An optical method to evaluate both mass and functional competence of pancreatic alpha- and beta-cells
Authors Wang, Yi
Han, Chengsheng
Zhu, Wenzhen
Wu, Zhengxing
Liu, Yanmei
Chen, Liangyi
Affiliation Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Wuhan 430074, Peoples R China.
Peking Univ, Inst Mol Med, Beijing Key Lab Cardiometab Mol Med, State Key Lab Membrane Biol, Beijing 100871, Peoples R China.
Keywords Insulin secretion
Glucagon secretion
Diabetes
alpha-cell mass
beta-cell mass
Islets
TYPE-2 DIABETES-MELLITUS
INSULIN-SECRETION
DELTA-CELLS
DB/DB MICE
ISLETS
HYPERGLUCAGONEMIA
HYPERGLYCEMIA
SENSITIVITY
HOMEOSTASIS
LANGERHANS
Issue Date 2016
Publisher JOURNAL OF CELL SCIENCE
Citation JOURNAL OF CELL SCIENCE.2016,129(12),2462-2471.
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 alpha- and beta-cell mass and function simultaneously. We firstly label both primary alpha- and beta-cells with the red fluorescent probe ZinRhodaLactam-1 (ZRL1), and then highlight alpha-cells by selectively quenching the ZRL1 signal from beta-cells. Based on the signals before and after quenching, we calculate the ratio of the alpha-cell to beta-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 alpha-cell to beta-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 alpha-cell mass prior to deterioration in functional beta-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.
URI http://hdl.handle.net/20.500.11897/433760
ISSN 0021-9533
DOI 10.1242/jcs.184523
Indexed SCI(E)
PubMed
Appears in Collections: 分子医学研究所
膜生物学国家重点实验室

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