Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus

Abstract

Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U-C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production.

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis—an animal experimental prospective cohort study

“…Due to the equal blood concentration of [18F]FDG reached by the i.p. injection [25, 26], the authors neither expect a better nor a worse visualization of tumors in respect to injection technique. Subsequently, a catheter was implanted to the nude rat’s jugular vein (24 gauge peripheral venous catheter, B. Braun Melsungen AG, Melsungen, Germany).…”

GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent

“…The serially collected blood samples were analyzed for 13C-glucose enrichment using GC-MS analysis. The % 13C glucose enrichments were then combined with the total glucose readings to calculate the concentration of 13C-glucose, and these values were modeled with a two-compartment model of whole body glucose metabolism to calculate the average EGP for the period from 0–150 minutes [ 17 ].…”

GPR120 suppresses adipose tissue lipolysis and synergizes with GPR40 in antidiabetic efficacy

“…Data were acquired by using selected ion monitoring under electron impact ionization (m/z 314-319, 10 ms dwell per ion). Relative quantities of glucose types were determined by comparing single-ion response ratios between each analyte with Mass-Hunter software (EnviroQuant module; Agilent) (22).…”