DiEn Yan1, YiNan Zhao1, XiuYing Gao1, YingSheng Zhou2. 1. Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China; Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, PR China. 2. Department of Endocrinology and Metabolism, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, PR China; Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing 100029, PR China. Electronic address: yszhou@ccmu.edu.cn.
Abstract
AIMS: To investigate insulin secretion and content in islet β cells after intravenous glucose load in mice. MATERIALS AND METHODS: Acute hyperglycemia (≥16.7 mmol/L) in C57BL/J6 mice was achieved by hyperglycemic clamp. Mice were divided into four groups: a 2-hour and a 4-hour high glucose-infusion (2 h-HG and 4 h-HG) with 25% dextrose groups and control groups with saline infusion of the same duration. Insulin levels and response were measured using intraperitoneal glucose tolerance test (IPGTT) in mice and glucose-stimulated insulin secretion (GSIS) for isolated islets after overnight culture. Immunohistochemistry and electron microscopy (EM) for islet β cells were used after the hyperglycemic clamp to study morphologic changes of insulin granules and to assess the impact of acute glucose load on islet histology. KEY FINDINGS: Blood glucose at 15, 30, 60 and 120 min was significantly higher in 4 h-HG compared with the other groups. Serum plasma insulin significantly decreased only at 15 min as a first-phase insulin response (FPIR). Insulin secretion at 2.8 and 16.7 mmol/L glucose stimulus in 4 h-HG group decreased 77% and 64% more than those in 2 h-HG, respectively (P<0.05). Similarly, residual insulin content in islet β cells after 2.8 and 16.7 mmol/L glucose challenge decreased 30% and 43% more than those in 2 h-HG, respectively (P<0.05). EM showed decreased insulin granules in islet cells and swollen mitochondria only in 4 h-HG. SIGNIFICANCE: Short time intravenous glucose load blunted FPIRs and decreased insulin content of islet β cells.
AIMS: To investigate insulin secretion and content in islet β cells after intravenous glucose load in mice. MATERIALS AND METHODS: Acute hyperglycemia (≥16.7 mmol/L) in C57BL/J6 mice was achieved by hyperglycemic clamp. Mice were divided into four groups: a 2-hour and a 4-hour high glucose-infusion (2 h-HG and 4 h-HG) with 25% dextrose groups and control groups with saline infusion of the same duration. Insulin levels and response were measured using intraperitoneal glucose tolerance test (IPGTT) in mice and glucose-stimulated insulin secretion (GSIS) for isolated islets after overnight culture. Immunohistochemistry and electron microscopy (EM) for islet β cells were used after the hyperglycemic clamp to study morphologic changes of insulin granules and to assess the impact of acute glucose load on islet histology. KEY FINDINGS:Blood glucose at 15, 30, 60 and 120 min was significantly higher in 4 h-HG compared with the other groups. Serum plasma insulin significantly decreased only at 15 min as a first-phase insulin response (FPIR). Insulin secretion at 2.8 and 16.7 mmol/L glucose stimulus in 4 h-HG group decreased 77% and 64% more than those in 2 h-HG, respectively (P<0.05). Similarly, residual insulin content in islet β cells after 2.8 and 16.7 mmol/L glucose challenge decreased 30% and 43% more than those in 2 h-HG, respectively (P<0.05). EM showed decreased insulin granules in islet cells and swollen mitochondria only in 4 h-HG. SIGNIFICANCE: Short time intravenous glucose load blunted FPIRs and decreased insulin content of islet β cells.
Authors: Zachary J Farino; Travis J Morgenstern; Julie Vallaghe; Nathalie Gregor; Prashant Donthamsetti; Paul E Harris; Nicolas Pierre; Robin Freyberg; Fabienne Charrier-Savournin; Jonathan A Javitch; Zachary Freyberg Journal: PLoS One Date: 2016-02-05 Impact factor: 3.240