Brain Glucose Sensors Play a Significant Role in the Regulation of Pancreatic Glucose-Stimulated Insulin Secretion
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Figures
- FIG. 1.
ICV infusion of glucose improved glucose handling during IVGTT. A and B: Schematic representation of experimental design. Vascular and third ventricle (ICV) catheters were implanted on day 1. Rats were acclimatized to the study room on day 6 and fasted overnight from 1500 hrs on day 6. On day 7, chronically catheterized rats underwent IVGTT (0.35 g/kg) preceded by ICV infusion of either 9-mg glucose or equimolar urea (n = 6–7) delivered over 30 min. C: ICV glucose rats showed reduced plasma glucose levels particularly during the first few minutes of IVGTT. D: In particular, the AUC0-10 (plasma glucose) was significantly (P < 0.05) lower in ICV glucose-treated rats relative to control urea-treated rats. E and F: Despite exposure to lower glycemia, plasma insulin responses were significantly greater in ICV glucose animals. Data are mean ± SEM. *P < 0.05. (A high-quality color representation of this figure is available in the online issue.)
- FIG. 2.
Ex vivo GK activity assays in protein preparations. A: Sigmoidal dependence of hepatic GK (n = 2) on glucose concentration. B: Glucose increases hypothalamic GK activity. C and D: GSN dose dependently inhibits hepatic (n = 3–5) and hypothalamic (n = 3) GK ex vivo. E: MH dose dependently inhibits hypothalamic GK ex vivo (n = 3), although with reduced potency as compared with GSN (IC50 =12 mM vs. 5 mM, MH vs. GSN, respectively). **P < 0.01.
- FIG. 3.
ICV infusion of a GK inhibitor, GSN-impaired glucose handling, and insulin secretion during IVGTT. A: Experimental design. On day 7, chronically catheterized (jugular vein and third ventricle) rats, which had been fasted overnight, underwent IVGTT (0.5 g/kg) preceded by 90-min ICV infusion of either GSN at 75 nmol/min or 150 nmol/min, or vehicle (aECF) (n = 9–13). B: ICV GSN rats showed impaired glucose handling, particularly during the first few minutes of IVGTT. C: The AUC0-10 (plasma glucose) increased significantly (P < 0.05) and dose-dependently in ICV GSN-treated rats as compared with ICV vehicle-treated rats. D and E: In spite of higher plasma glucose levels in ICV GSN-infused rats, plasma insulin levels were reduced significantly and dose-dependently relative to vehicle-treated rats. Insulinogenic index was also significantly reduced by both ICV 150 and 75 nmol/min treatment as compared with ICV aECF. Data are mean ± SEM. *P < 0.05; **P < 0.01 (A high-quality color representation of this figure is available in the online issue.)
- FIG. 4.
ICV infusion of a GK inhibitor, MH, impairs insulin secretion during IVGTT. A: ICV MH rats showed impaired glucose handling, particularly during the first few minutes of IVGTT. B: The AUC0-10 (plasma glucose) was significantly (P < 0.05) higher in ICV MH-treated rats as compared with ICV vehicle-treated rats. C and D: In spite of higher plasma glucose levels in ICV GSN-infused rats, plasma insulin levels were reduced relative to vehicle-treated rats. Insulinogenic index was significantly reduced by both ICV 300 nmol/min MH treatment as compared with ICV aECF. Data are mean ± SEM (n = 9–13). *P < 0.05. (A high-quality color representation of this figure is available in the online issue.)
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