Fig. 1.

Low-dose parenteral glucose induces hyperglycemia and pancreatic dysfunction in septic mice. (A) Mice underwent either sham surgery (Sham) or cecal ligation and puncture (CLP) and received intravenous infusion of saline (Sal) or dextrose (Dex). Blood glucose was measured at 24 h following surgery (n ≥ 20 in sham groups and n ≥ 16 in CLP groups). Mice undergoing CLP and receiving dextrose demonstrated a dichotomous response with half of the group maintaining euglycemia (CLP Dex Eug, <200 mg/dL; n = 75) and the other half developing either hyperglycemia (CLP Dex Hyp, 200–599 mg/dL; n = 18) or severe hyperglycemia (CLP Dex Sev, ≥600 mg/dL; n = 20). (B) Plasma insulin levels are similar 24 h after sham surgery (Sham Sal, Sham Dex, n ≥ 7) or after CLP in the setting of saline infusion (CLP Sal, n ≥ 6). In contrast, circulating insulin is significantly increased in all CLP mice receiving dextrose (CLP + Dex) compared with CLP Sal mice (p = 0.003 by 1-way ANOVA). Plasma insulin levels were similar between CLP + Dex mice in Eug, Hyp, and Sev groups (p > 0.05 by 1-way ANOVA). (C) Plasma insulin levels increase with elevations in blood glucose for CLP Sal and CLP + Dex Eug groups (Slope = 0.045 ± 0.01 (p < 0.001 compared with zero, r² = 0.32)). However, for mice in CLP + Dex Hyp and CLP + Dex Sev groups, higher blood glucose levels do not result in corresponding increases in plasma insulin (Slope = –0.009 ± 0.004 (p = 0.1 compared with zero, r² = 0.64)). (D) Paraffin sections of pancreas stained with hematoxylin and eosin (H&E) (top panels) demonstrate islets with normal morphology independent of development of hyperglycemia. Immunofluorescence for insulin (green) and activated caspase 3 (act-Casp3) (red) confirmed that very few beta cells showed signs of apoptotic cell death (bottom panels) in septic mice exposed to dextrose infusion.