Endotoxemia Impairs Compensatory Pancreatic Beta Cell Secretory Function In Mildly Hyperglycemic Mice

Abstract

Optimizing glucose and insulin metabolism in sepsis and critical illness remains a clinical and scientific dilemma. We previously Rationale: demonstrated that mortality in a hyperglycemic mouse model of sepsis may be related to impaired pancreatic function. Using a novel frequently sampled intravenous glucose tolerance test (FSIVGTT) in conscious mice, we subsequently observed that endotoxemia leads to profound glucose intolerance and insulin resistance only under the condition of mild hyperglycemia. We now extend this work to further investigate the role of the pancreatic response in the metabolic dysfunction observed in critical illness.Adult male C57BL/6NTac mice were instrumented with chronic indwelling arterial and venous catheters. After 3 days recovery Methods: from surgery, four groups of mice were either infused with glucose (D50) to elicit mild hyperglycemia or saline at 100 ul/hr for 24 hours before acute intra-arterial administration of endotoxin (LPS, 1 mg/kg) or vehicle. Five hours after LPS administration, an FSIVGTT was performed by rapidly sampling arterial blood for glucose (and insulin) at (