Acute intravenous glucose load impairs early insulin secretion and insulin content in islet β cells in mice
2016
Yan, DiEn | Zhao, YiNan | Gao, XiuYing | Zhou, YingSheng
To investigate insulin secretion and content in islet β cells after intravenous glucose load in mice.Acute hyperglycemia (≥16.7mmol/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 (2h-HG and 4h-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.Blood glucose at 15, 30, 60 and 120min was significantly higher in 4h-HG compared with the other groups. Serum plasma insulin significantly decreased only at 15min as a first-phase insulin response (FPIR). Insulin secretion at 2.8 and 16.7mmol/L glucose stimulus in 4h-HG group decreased 77% and 64% more than those in 2h-HG, respectively (P<0.05). Similarly, residual insulin content in islet β cells after 2.8 and 16.7mmol/L glucose challenge decreased 30% and 43% more than those in 2h-HG, respectively (P<0.05). EM showed decreased insulin granules in islet cells and swollen mitochondria only in 4h-HG.Short time intravenous glucose load blunted FPIRs and decreased insulin content of islet β cells.
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