title: Acute intravenous glucose load impairs early insulin secretion and insulin content in islet β cells in mice.
abstract: OBJECTIVE
  To investigate insulin secretion and content in islet β cells after intravenous glucose load in mice.
  
  
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Short time intravenous glucose load blunted FPIRs and decreased insulin content of islet β cells.
authors.affiliation: 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.
authors.forename: DiEn
authors.initials: D
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: YiNan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: XiuYing
authors.initials: X
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: YingSheng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006943:Hyperglycemia / Q000139:chemically induced / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose
keywords: Acute hyperglycemia; GSIS; IPGTT; Insulin granules