Metabolic, stress, and inflammatory biomarker responses to glucose administration in Fischer-344 rats: intraperitoneal vs. oral delivery.

INTRODUCTION: Metabolic effects of anthropogenic chemicals are a focus of environmental health research due to the significant public health implications. Conventional glucose tolerance tests (GTTs) do not generally examine multiple metabolic, inflammatory, and endocrine factors; however, responses to exogenous glucose can provide insight into mode-of-action and disease processes, and warrant consideration in developing models for toxicological assessment.

METHODS: GTTs were conducted on male Fischer-344 rats to 1) assess the feasibility of measuring multiple analytes in small sample volumes; 2) monitor analyte response; and 3) determine whether route of glucose delivery (oral, OGTT vs. intraperitoneal, IPGTT, 2g/kg) modified responses. Plasma samples (0, 30, 60, 90, 120min post-glucose administration) were analyzed for triglycerides; hormones involved in glucose regulation (insulin, glucagon, glucagon-like peptide (GLP)-1)), energy homeostasis (ghrelin, leptin), and stress response (corticosterone); cytokines (TNF, IL-6); and markers of endothelial dysfunction (VEGF, PAI-1).

RESULTS: Glucose peaked at 30min during the IPGTT but not the OGTT (p<0.001), a trend paralleled by insulin, while triglycerides decreased following the IPGTT (transient) and the OGTT (sustained). GLP-1 was transiently decreased while ghrelin and leptin levels increased progressively during the IPGTT alone. Corticosterone was increased during both the IPGTT (sustained) and OGTT (transient). TNF and VEGF were unchanged, while PAI-1 and IL-6 were not detected. Increasing the oral glucose dose to 3g/kg did not significantly alter profiles.

DISCUSSION: Results confirm the feasibility of measuring multiple analytes during a GTT, and indicate that administration of glucose can impact metabolic and endocrine profiles in a route-dependent manner.