Isotope Tracing Research On Glucose And Lipid Metabolic Regulation

Part one Tracing the glucose fluxes of Streptozotocin-induced type1diabeticrats with stable and radioactive isotopesObjective Blood glucose concentrations of type1diabetic rats are vulnerable,especially to stress and trauma. The present study aimed to investigate the fastingendogenous glucose production and skeletal muscle glucose uptake of Streptozotocin-induced type1diabetic rats using an unstressed vein and artery implantation ofcatheters at the tails of the rats as a platform.Methods Streptozotocin (65mg·kg-1) were administered to induce type1diabeticstate. The unstressed approach of catheters of vein and artery at the tails of the rats wasestablished before the isotope tracer injection. Dynamic measurement of fastingendogenous glucose production was assessed by continuously infusing stable isotope[6,6-2H2] glucose, while skeletal muscle glucose uptake by bolus injectingradioactively labeled [1-14C]-2-deoxy-glucose.Results Streptozotocin-induced type1diabetic rats displayed polydipsia, polyphagia,polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhancedfasting endogenous glucose production and reduced glucose uptake in skeletal musclecompared to non-diabetic rats.Conclusions The dual catheters implantation at the tails of the rats together withisotope tracers injection is a save time, unstressed and feasible approach to explore theglucose metabolism in animal models in vivo. Part two Tracing glucose fluxes of prediabetic individuals using stable isotopesObjective: This study was undertaken to determine whether the endogenous glucoseproduction (EGP), oral glucose rate of appearance (Ra) and glucose rate ofdisappearance (Rd) were different in Chinese individuals with prediabetes under fastingconditions and following an oral glucose challenge.Methods: Each group (type2diabetes, prediabetes, or non-diabetic groups) with5subjects matched for age, weight, fat free mass and body mass index underwent a180min stable glucose isotope tracing study under fasting and after ingestion of a75g oralglucose load. Isotope glucose enrichment was measured by gas chromatography-massspectrometry. Insulin sensitivity was estimated using the OGTT-derived insulinsensitivity index, β cell function was determined by the insulinogenic index(ΔI30/ΔG30).Results: The insulin sensitivity index (P=0.043) and insulinogenic index (P=0.021)were decreased in subjects with prediabetes compared to non-diabetes. Fasting EGPwas slightly higher (P=0.29) in subjects with prediabetes than non-diabetes.Postprandial nadir EGP occurred later in prediabetic than non-diabetic subjects. Ra didnot differ among the three groups. Rd was substantially lower in subjects withprediabetes than non-diabetes after glucose intake (P=0.013).Conclusions: The postprandial mild hyperglycemia observed among prediabetes mayresult from decreased Rd. Part three Tracing lipid fluxes of β2-adrenergic receptor polymorphisms using radioactive isotopeObjective:The β2-adrenergic system is an important regulator of human adipose tissue lipolysis. Polymorphisms that result in amino acid substitutions in the β2-adrenergic receptor have been reported to alter lipolysis.Methods:We hypothesized that variations in the amino acid at position16of the β2-adrenergic receptor would result in different lipolytic responses to intravenous epinephrine and exercise.17volunteers homozygous for glycine at position16(Gly/Gly,9female) and16volunteers homozygous for arginine at position16(Arg/Arg,8female) of the β2-adrenergic receptor participated in this study. On one study day participants received infusions of epinephrine at submaximal (5ng·kg-1·min-1) and maximal (40ng·kg-1·min-1) lipolytic doses.[9,10-3H] palmitate was infused both days to measure free fatty acid-palmitate kinetics.Results:Palmitate release rates in response to epinephrine and exercise were not different in the Gly/Gly and Arg/Arg participants. The only statistically significant difference we observed was a lesser AVO2in Arg/Arg volunteers in response to the submaximal epinephrine infusion.Conclusion:The polymorphisms resulting in Arg/Arg and Gly/Gly at position16of the β2-adrenergic receptor do not result in clinically meaningful differences in lipolysis responses to epinephrine or submaximal exercise.