The Role of Gluconeogenesis in Regulating Naturally High Plasma Glucose Concentrations in Mourning Doves

Birds have been found to possess naturally high blood glucose levels compared to other mammals of similar sizes (Braun and Sweazea, 2008). Additionally, birds utilize lipids as their primary source of fuel yet continue to have high resting blood glucose levels (Landys et al., 2005). It has been hypothesized that the underlying cause of this is a preference to oxidize fatty acids rather than carbohydrates, which results in the production of glycerol (a precursor to gluconeogenesis). Thus, the role of gluconeogenesis in blood glucose regulation in birds was examined in this study. We captured seven mourning doves (Zenaida macroura) in Tempe, Arizona, and allowed them to acclimate to their new environment for two weeks. One bird was released prior to experimentation due to poor acclimation. Over a course of six weeks following this acclimation period, birds were administered either metformin (an inhibitor of gluconeogenesis that is commonly used in type 2 diabetes patients) at 150 mg/kg or 300 mg/kg, a compound called DAB (1,4-dideoxy-1,4-imino-D-arabinitol) at a dose of 2.5 mg/kg that acts to inhibit glycogenolysis (a potential compensatory mechanism that elevates blood sugar), or a control (water). Blood draws were conducted at 0, 5, and 15 minutes following each treatment. In this crossover design study, each bird received one treatment each week. In the first phase of this study, Kreisler et al. found that 150 mg/kg metformin significantly increased blood glucose whereas 300 mg/kg metformin did not increase over two hours. These observations held true in the current acute study as well. Additionally, Kreisler et al. observed no effect of METDAB (150 mg/kg metformin and 2.5 mg/kg DAB) on blood glucose compared to the control, indicating that DAB effectively inhibited glycogenolysis induced by metformin. Contrary to this, the current study observed a significant increase (p<0.05) in blood glucose over 15 minutes after administration of METDAB, suggesting that DAB does not act within a shorter period of time. While metformin increases blood glucose within only 5 minutes, the longer timeframe with which DAB acts was not sufficient to prevent the increase. Additionally, when administered alone, DAB had no effect on blood glucose concentrations over a 2-hour period. This suggests that glycogenolysis is most likely not activated in healthy mourning doves under fed conditions and that gluconeogenesis plausibly plays a much larger role.