Alan Cherrington

..The primary effect of insulin on the liver is its direct action...

..Hepatic glucose uptake is enhanced by the portal delivery of glucose, which creates a negative arterioportal substrate gradient. Hepatic amino acid (AA) utilization may be regulated by the same phenomenon, but this has not been proven...

..In conclusion, in conscious dogs with successfully auto-transplanted islets, the beta cell response to mild non-insulin-induced hypoglycemia was normal, whereas the alpha cell response was not...

..9+/-0.4) and failed to increase significantly (3.2+/-0.2) during P2 (not significant vs. CON). Selective sympathetic denervation increased NHGU during hyperglycemia but significantly blunted the response to portal glucose delivery...

..7 +/- 1.0 and 5.4 +/- 0.8 micromol.kg(-1).min(-1), respectively, P < 0.05). In conclusion, physiological GLP-1 levels increase glucose disposal in the liver, and this effect does not involve GLP-1 receptors located in the portal vein...

..These provocative data suggest that the indirect effects of insulin on the liver are the primary determinant of HGP in mice...

..6 +/- 0.9 mg x kg(-1) x min(-1); 65 min). Insulin kinetics and areas under the curve were identical in both groups. These data suggest that inhalation of Exubera results in a unique action on nonhepatic glucose clearance...

..Thus the loss of insulin pulsatility per se likely has little or no impact on the effectiveness of insulin in regulating liver glucose uptake...

..Intraportal 5-HTP enhances NHGU without significantly altering nonhepatic glucose uptake or causing gastrointestinal side effects, raising the possibility that a related agent might have a role in reducing postprandial hyperglycemia...

..HIM2 was more effective than Humulin, perhaps because its lowered clearance caused higher levels at the liver and periphery and its biological activity was not reduced proportionally to its decreased clearance...

..In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised...

..05). Intraportal fluvoxamine enhanced NHGU and net hepatic carbon retention in the presence of hyperinsulinemia but not euinsulinemia, suggesting that hepatocyte-targeted SSRIs may reduce postprandial hyperglycemia...

..Sensitivity of the liver was not enhanced by increased insulin delivery to the head. Thus, this study demonstrates that the direct effects of insulin dominate the acute regulation of HGP in the normal dog...

..Thus elevated NEFA limit the initial increase in glucagon-stimulated HGO by blunting glycogenolysis, without having any effect on the gluconeogenic or glycogenolytic contributions or NHGO thereafter...

..This study demonstrates that the GC receptor plays an important role in the regulation of basal hepatic glucose production and represents a significant potential therapeutic target...

..05). There were no significant differences between groups in the total glucose infusion rate. Thus, intraportal NPY stimulates net hepatic glucose uptake without significantly altering whole body glucose disposal in dogs...

..023, and 0.122 +/- 0.021 during P1, P2, and P3, respectively (P < 0.05 vs. control during P2 and P3), with no significant difference in glucose infusion rates. Thus, NOS inhibition enhanced NHFE, an effect partially reversed by SIN-1...

..This indicates that a physiological increase in GLP-1 augments glucose utilization only when GLP-1 and glucose gradients conditions mimic the postprandial state...

..2 vs. 27.1 +/- 1.5 and 26.1 +/- 1.0 mumol.kg(-1).min(-1)). Nonhepatic glucose uptake did not change in response to saline or SIN-1 infusion. In conclusion, portal but not peripheral infusion of the nitric oxide donor SIN-1 inhibited NHGU...

..GLP-1 infusion increased glucose disposal independently of changes in pancreatic hormone secretion but only when the peptide was delivered intraportally...

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..005), the latter representing calculation of spillover between arterial and hepatic venous blood without portal venous data. Metabolism of chylomicron triglycerides in visceral fat may be an important source of portal venous FFAs...

..1+/-0.9, 1.6+/-0.6, 2.4+/-0.7, and 1.5+/-0.3 mg/kg/min, respectively, due to inhibition of glycogenolysis. In conclusion, NNC 25-0926 effectively blocked the ability of glucagon to increase HGP in the dog...

..Pulmonary administration of insulin increases nonhepatic glucose uptake compared with infusion, and skeletal muscle is the likely site of that effect...

..INH administration resulted in increased insulin sensitivity in nonhepatic but not in hepatic tissues compared with s.c. delivery...

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..Therefore, after an overnight fast in the conscious dog, the kidneys do not significantly contribute to overall glucose production or respond to glucagon or epinephrine...

..1) to increase during GLP-1 infusion at 20 pmol. kg(-1). min(-1) (24% greater than control). Intraportal infusion of GLP-1 at high physiological and pharmacological rates increased glucose disposal primarily in nonhepatic tissues...

..In conclusion, increased FFA markedly changed the mechanism by which EPI stimulated hepatic glucose production, suggesting that its overall lipolytic effect may be important in determining its effect on the liver...

..We conclude that in the absence of appreciable glycogen breakdown, an acute gluconeogenic effect of hypoinsulinemia becomes manifest, whereas inhibition of the process by a physiologic rise in insulin was not evident...

..9 +/- 0.3 to 1.3 +/- 0.3 mg. kg(-1). min(-1) in the Cool group. Hepatic gluconeogenesis did not change in either group. These data suggest that vagal blockade acutely modulates hepatic glucose production by inhibiting glycogenolysis...

..This difference was most apparent in the steroid-treated group, where the combination of the two methods (GNG(flux)) detected a significant increase in gluconeogenic flux...

..Thus, activation of the Po glucose signal appears to inhibit the shift toward sympathetic dominance that would otherwise result, thereby causing an incretin effect...

..Thus, a difference of approximately 120 pmol/l in arterial insulin completely abolished the response of the alpha-cell to mild hypoglycemia...

..05 vs. BI) in BI, PoI, and PeI, respectively. Both direct and indirect insulin actions increase NHGU, but the rise in hepatic sinusoidal insulin appears critical for efficient storage of glucose as hepatic glycogen...

..Therefore, we hypothesized that the combination of immunosuppressive therapy and hepatic denervation would create additional alterations in the disposition of glucose from a mixed meal...

..In addition, they confirmed the ability of second-phase insulin release to have significant effects on both glucose production and utilization...

..As a result, postprandial hyperglycemia and insulin release by the pancreatic beta-cell were reduced. In conclusion, catalytic amounts of fructose have the ability to improve glucose tolerance...

..In conclusion, an increase in plasma FFA and glycerol significantly inhibited hepatic glycogenolysis and markedly stimulated hepatic gluconeogenesis...

..Additionally, glucagon exerted its full glycogenolytic effect, whereas epinephrine exerted its full gluconeogenic effect, such that both processes increased significantly during concurrent hormone administration...

..08). Thus, in the presence of both hormones, and when the gluconeogenic precursor supply is maintained, gluconeogenic flux is potentiated and glycogenolytic flux is inhibited...

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..36 units/kg subcutaneous insulin. In addition, arterial peak concentration following insulin inhalation is two times greater than subcutaneous injection; however, the insulin is present in the circulation for half the time...

..Gel retardation assays demonstrate that this CRE binds several transcription factors including CRE-binding protein and CCAAT enhancer-binding protein...

..In the presence of hyperglycemia and relative insulin deficiency, elevated NEFAs reduce NHGU by stimulating hepatic glucose release and suppressing hepatic glucose uptake...

..SAL), and 34.7 +/- 7.7 (P < 0.05 vs. SAL). Intraportal 5-HT enhances NHGU but blunts nonhepatic glucose uptake, raising the possibility that hepatic-targeted 5-HT or 5-HT receptor agonists might reduce postprandial hyperglycemia...

..Additionally, the translocation of GK is induced by the postprandial rise in plasma glucose and insulin...

..We conclude that, in the absence of appreciable glycogen breakdown, the increase in glycolytic flux that accompanies hyperglycemia results in decreased net carbon flux to G-6-P but no effect on gluconeogenic flux to G-6-P...

..Clearly, a fall in the portal vein insulin level is not required for a normal alpha-cell response to mild, non-insulin-induced hypoglycemia...

..As a result, both groups maintained near-euglycemia. The dog glucoregulates more rigorously than the mouse in response to both portal and peripheral glucose delivery...

..Exercise stimulates insulin-dependent and -independent muscle glucose uptake, as well as the liver's ability to take up glucose...

..This review summarizes the recent work suggesting that fructose enhances glucose tolerance by augmenting liver glucose uptake. This increase may be mediated by the translocation and activation of hepatic glucokinase...

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..05 vs. Sham-Sal), 9.8 +/- 0.9 (P < 0.05 vs. Sham-Sal), and 13.6 +/- 1.8 mg. kg(-1) x min(-1), respectively. DN caused peripheral insulin resistance, and intraportal but not peripheral acetylcholine restored insulin sensitivity...

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..The answers obtained by the proposed studies should enhance our understanding of the control of glucose production and pancreatic function in vivo. ..

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..The proposed experiments will increase our understanding of the role of the liver in postprandial glucose disposal and should yield insight into the role of the nervous system in controlling fuel disposition after feeding...

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