mechanism of glucagon choleresis in guinea pigs

1990 ◽  
Vol 259 (5) ◽  
pp. G736-G744 ◽  
Author(s):  
R. Lenzen ◽  
V. J. Hruby ◽  
N. Tavoloni

The present studies were carried out to clarify the mechanism of glucagon choleresis in guinea pigs. At the infusion rate of 1.4 nmol.min-1.kg-1, glucagon increased bile flow from 206.6 +/- 14.3 to 302.6 +/- 35.0 microliters.min-1.kg-1 and bicarbonate biliary concentration from 63.7 +/- 4.2 to 75.5 +/- 5.9 meq/l. Measurements of bile acid excretion in bile, the biliary tree volume, and of the hormone choleretic effect in guinea pigs with proliferated bile ductules/ducts induced by alpha-naphthylisothiocyanate feeding indicated that glucagon, unlike secretin, stimulated canalicular bile flow. Inhibition of prostaglandin synthesis by indomethacin administration (5 mg.kg-1.h-1) did not modify the choleretic effect of glucagon, and infusion of a glucagon analogue (TH-glucagon, 1.4 nmol.min-1.kg-1), which did not increase hepatic formation of adenosine 3'5'-cyclic monophosphate (cAMP), failed to stimulate bile flow. Like the parent hormone, however, TH-glucagon augmented plasma glucose levels and stimulated formation of inositol phosphates. Colchicine pretreatment (0.5 mg/kg ip) almost entirely prevented the choleretic effect of glucagon but did not modify spontaneous and bile acid-induced bile flow and the stimulatory effect of the hormone on glucose release and on hepatic formation of cAMP and inositol phosphates. Finally, glucagon produced a large increase in the biliary entry of horseradish peroxidase, even though this effect was transient and was not coupled to the increase in bile flow. These results indicate that glucagon choleresis in the guinea pig is not secondary to prostaglandin release, is canalicular in origin, involves bicarbonate secretion, is mediated by cAMP, and requires an intact microtubular system.

1991 ◽  
Vol 260 (1) ◽  
pp. G167-G174
Author(s):  
W. G. Hardison ◽  
E. Dalle-Molle ◽  
E. Gosink ◽  
P. J. Lowe ◽  
J. H. Steinbach ◽  
...  

To determine the effects of alteration of biliary paracellular permeability on bile flow and composition, we measured the biliary outputs of compounds highly concentrated in bile, all infused at a constant rate in the isolated rat liver perfused with Krebs-Henseleit buffer in a one-pass fashion. Paracellular permeability was increased by infusing 10(-8) M vasopressin (VP). The cholephilic compounds were three cations of various molecular weights, tributylmethylammonium (TBuMA), N-acetylprocainamide ethobromide (APAEB), and propidium iodide, and two anions, taurocholate (TC), a micelle-forming bile acid, and taurodehydrocholate (TDHC), an nonmicelle former. When TC was infused and paracellular permeability increased with VP, neither bile flow nor TC output changed, whereas outputs of cations fell. When TDHC was infused, TDHC output fell, as did outputs of all cations. The decrements in cation outputs exceeded that of TDHC and were inversely related to the molecular weight of the cation. To document that these changes were not related to reduced uptake of these compounds, we tested the uptakes of TBuMA, APAEB, and TDHC into isolated hepatocytes. In no case did 10(-8) M VP significantly reduce uptake. The data demonstrate that micelle-forming bile acids, with their high effective molecular weights, do not efflux from the biliary tree when permeability is increased with VP, whereas nonmicelle-forming bile acids do. Cations efflux more readily than anions, and within this group efflux rate is inversely related to molecular weight. The data confirm the size and charge selectivity of biliary tree permeability.(ABSTRACT TRUNCATED AT 250 WORDS)


1984 ◽  
Vol 247 (5) ◽  
pp. G527-G536 ◽  
Author(s):  
N. Tavoloni

The biliary permeation of polar nonelectrolytes was studied in anesthetized, bile duct-cannulated guinea pigs with functional cholecystectomy and nephrectomy. During spontaneous secretion, the steady-state bile-to-plasma ratio (B/P) of [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin was 1.02, 0.90, 0.38, 0.12, and 0.04, respectively. Differently structured hydroxy bile acids, but not taurodehydrocholate, reversibly diminished [14C]erythritol and [14C]mannitol B/P during choleresis, and with some of them, particularly taurocholate and glycochenodeoxycholate, the biliary clearance of either solute declined below precholeretic levels. For any given hydroxy bile acid, the degree of B/P diminution was directly related to the molecular radii of these two inert carbohydrates. All bile acids failed to decrease [14C]urea, [3H]sucrose, and [3H]inulin B/P. On the contrary, most of them irreversibly increased [3H]sucrose and [3H]inulin permeability. These results suggest that in the guinea pig 1) hydroxy bile acids diminish the size or rearrange the architecture of the canalicular membrane "aqueous pores" through which [14C]erythritol and [14C]mannitol enter the canaliculus, and 2) solutes of the size of or smaller than [14C]mannitol enter bile primarily through a transcellular route, whereas [3H]sucrose, and [3H]inulin permeate mainly via a transjunctional shunt pathway. These studies indicate that [14C]erythritol and [14C]mannitol cannot be used to estimate canalicular bile flow in this species.


1985 ◽  
Vol 63 (10) ◽  
pp. 1245-1251 ◽  
Author(s):  
Nicola Tavoloni

To define the role of inorganic electrolyte secretion in hepatic bile formation, the effects of secretin, glucagon, and differently structured bile acids on bile flow and composition were studied in the dog, guinea pig, and rat. In the dog and guinea pig, secretin (2.5–10 clinical units∙kg−1∙30 min−1) increased bile flow and bicarbonate concentration in bile, a finding consistent with the hypothesis that the hormone stimulates a bicarbonate-dependent secretion possibly at the level of the bile ductule–duct. In the rat, secretin (5–15 CU∙kg−1∙30 min−1) failed to increase bile secretion. Glucagon (1.25–300 μg∙kg−1∙30 min−1) increased bile flow in all the three species, and produced no changes in biliary bicarbonate concentrations in the dog and rat. In the guinea pig, however, glucagon choleresis was associated with an increase in bicarbonate concentration in bile, similar to that observed with secretin. The choleretic activities of various bile acids (taurocholate, chenodeoxycholate, glycochenodeoxycholate, tauroursodeoxycholate, and ursodeoxycholic acid, infused at 30–360 μmol∙kg−1∙30 min−1) were similar in the rat (6.9–7.2 μL/μmol), but different in the guinea pig (11–31 μL/μmol). In the latter species, the more hydrophobic the bile acid, the greater was its choleretic activity. In all instances, bile acid choleresis was associated with a decline in the biliary concentrations of chloride, but with no major change in bicarbonate levels. The prominent finding of these studies is that, regardless of whether bile flow was stimulated by hormones or different bile acids, bicarbonate concentrations in bile were always similar to or higher than those in plasma. This is construed to support the view that bicarbonate is transported into bile, possibly at multiple sites within the biliary tree. Its excretion most likely provides the driving force for hormone-induced choleresis, and may in part account for the flow of bile associated with bile acid secretion.


2020 ◽  
Vol 16 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Bozica Kovacevic ◽  
Corina Mihaela Ionescu ◽  
Giuseppe Luna ◽  
...  

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.


2003 ◽  
Vol 19 (5) ◽  
pp. 371-375 ◽  
Author(s):  
A. Delarue ◽  
M. F. Gerhardt ◽  
T. Merrot ◽  
B. Roquelaure ◽  
J. M. Guys ◽  
...  

1990 ◽  
Vol 269 (3) ◽  
pp. 781-788 ◽  
Author(s):  
M J Smit ◽  
A M Temmerman ◽  
R Havinga ◽  
F Kuipers ◽  
R J Vonk

The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.


1961 ◽  
Vol 200 (2) ◽  
pp. 313-317 ◽  
Author(s):  
Leon Lack ◽  
I. M. Weiner

The transport of taurocholic and glycocholic acids by the small intestine of rats and guinea pigs against a concentration gradient was studied by the everted gutsac technique. Transport of these substances is limited to the distal ileal segment. This transport is inhibited by anoxia, dinitrophenol and sodium azide. The system has a transport maximum. On the basis of these criteria bile acid reabsorption is considered to occur by active transport.


Author(s):  
M. A. Shorikov ◽  
O. N. Sergeeva ◽  
M. G. Lapteva ◽  
N. A. Peregudov ◽  
B. I. Dolgushin

Proximal extrahepatic bile ducts are the biliary tree segment within formal boundaries from cystic ductcommon hepatic duct junction to sectoral hepatic ducts. Despite being a focus of attention of diagnostic and interventional radiologists, endoscopists, hepatobiliary surgeons and transplantologists they weren’t comprehensively described in available papers. The majority of the authors regard bile duct confluence as a group of merging primitively arranged tubes providing bile flow. The information on the proximal extrahepatic bile duct embryonal development, variant anatomy, innervation, arterial, venous and lymphatic supply is too general and not detailed. The present review brought together and systemized exiting to the date data on anatomy and function of this biliary tract portion. Unique, different from the majority of hollow organs organization of the proximal extrahepatic bile duct adapts them to the flow of the bile, i.e. viscous aggressive due to pH about 8.0 and detergents fluid, under higher wall pressure than in other parts of biliary tree. 


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