scholarly journals Intravenous Glucose Administration in Fasting Rats Has Differential Effects on Acylated and Unacylated Ghrelin in the Portal and Systemic Circulation: A Comparison between Portal and Peripheral Concentrations in Anesthetized Rats

Endocrinology ◽  
2007 ◽  
Vol 148 (11) ◽  
pp. 5278-5287 ◽  
Author(s):  
Carlotta Gauna ◽  
Piet Uitterlinden ◽  
Piet Kramer ◽  
Rosalie M. Kiewiet ◽  
Joop A. M. J. L. Janssen ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Metabolic Regulation ◽  
Glucose Tolerance Test ◽  
Hepatic Clearance ◽  
Systemic Circulation ◽  
Tolerance Test ◽  
Hepatic Extraction ◽  
Intravenous Glucose ◽  
Nutritional Factors ◽  
Unacylated Ghrelin

Ghrelin is produced by the gastrointestinal tract, and its systemic concentrations are mainly regulated by nutritional factors. Our aim was to investigate: 1) endogenous portal and systemic acylated and unacylated ghrelin levels (AG and UAG, respectively); 2) whether an iv glucose tolerance test (IVGTT) modifies AG and UAG; and 3) whether the liver passage plays a role in regulating systemic AG and UAG. To elucidate this, we evaluated the effects of IVGTT or saline injection on endogenous portal and systemic concentrations of glucose, insulin, AG, and UAG in anesthetized fasting rats. Hepatic extraction of insulin, AG, and UAG and the ratio of AG to UAG were also measured. IVGTT suppressed both portal (P < 0.03) and peripheral (P < 0.05) UAG, whereas it only blunted prehepatic, but not peripheral, AG. During fasting, hepatic clearance of UAG was 11%, and it was decreased to 8% by IVGTT. AG was cleared by the liver by 38% but unaffected by glucose. The AG to UAG ratio was higher in the portal than the systemic circulation, both in the saline (P < 0.004) and IVGTT (P < 0.0005) rats. In conclusion, this study shows that: 1) the ratio of AG to UAG is very low in the portal vein and decreases further in the systemic circulation; 2) IVGTT in anesthetized fasting rats inhibits UAG, whereas it only blunts prehepatic, but not systemic, AG; and 3) hepatic clearance of AG is much higher than that of UAG. Thus, our results suggest that peripheral AG metabolic regulation and action are mainly confined within the gastrointestinal tract.

Unacylated ghrelin acts as a potent insulin secretagogue in glucose-stimulated conditions

2007 ◽  
Vol 293 (3) ◽  
pp. E697-E704 ◽  
Author(s):  
Carlotta Gauna ◽  
Rosalie M. Kiewiet ◽  
Joop A. M. J. L. Janssen ◽  
Bedette van de Zande ◽  
Patric J. D. Delhanty ◽  
...  
Keyword(s):  
Insulin Response ◽  
Gut Hormones ◽  
Systemic Circulation ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Unacylated Ghrelin ◽  
Ghrelin Receptor ◽  
Insulin Secretagogue ◽  
Ghrelin Receptor Antagonist

Acylated and unacylated ghrelin (AG and UAG) are gut hormones that exert pleiotropic actions, including regulation of insulin secretion and glucose metabolism. In this study, we investigated whether AG and UAG differentially regulate portal and systemic insulin levels after a glucose load. We studied the effects of the administration of AG (30 nmol/kg), UAG (3 and 30 nmol/kg), the ghrelin receptor antagonist [d-Lys3]GHRP-6 (1 μmol/kg), or various combinations of these compounds on portal and systemic levels of glucose and insulin after an intravenous glucose tolerance test (IVGTT, d-glucose 1 g/kg) in anesthetized fasted Wistar rats. UAG administration potently and dose-dependently enhanced the rise of insulin concentration induced by IVGTT in the portal and, to a lesser extent, the systemic circulation. This UAG-induced effect was completely blocked by the coadministration of exogenous AG at equimolar concentrations. Similarly to UAG, [d-Lys3]GHRP-6, alone or in combination with AG and UAG, strongly enhanced the portal insulin response to IVGTT, whereas exogenous AG alone did not exert any further effect. Our data demonstrate that, in glucose-stimulated conditions, exogenous UAG acts as a potent insulin secretagogue, whereas endogenous AG exerts a maximal tonic inhibition on glucose-induced insulin release.

APPLICATION DE LA DOUBLE ÉPREUVE D'HYPERGLYCÉMIE INTRAVEINEUSE À L'ÉTUDE DU DIABÈTE

1960 ◽  
Vol XXXIII (II) ◽  
pp. 157-167
Author(s):  
T. Rodari ◽  
G. Specchia
Keyword(s):  
Glucose Tolerance ◽  
Pancreatic Islet ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Intravenous Glucose Tolerance Test ◽  
Intravenous Glucose ◽  
Intravenous Glucose Tolerance ◽  
Glucose Assimilation

ABSTRACT The double intravenous glucose tolerance test does not modify the assimilation coefficient in normal and thin diabetic subjects. On the contrary, in fat diabetic subjects the second coefficient of assimilation increases significantly, but not the first one. From these researches it is evident that the valuation of glucose assimilation by double venous hyperglycaemic test indicates the functional behaviour of the pancreas in different diabetic states. The interpretation of this behaviour of pancreatic islet response to the double venous hyperglycaemic test is discussed.

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