The effect of glucagon, dibutyrylic cyclic AMP and insulin on bile production in the intact rat and the perfused rat liver

Thomsen, Ole Østergaard; Larsen, Jørgen Falck

doi:10.1111/j.1748-1716.1981.tb06700.x

Cited by 34 publications

(8 citation statements)

References 16 publications

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“…Glucagon increased the rate of CP-/HCO exchange by 100% when meastred during Cl -removal or by 50% after Cl -readmission. In comparison, the excretion rates of bicarbonate in bile were increased by 34% in the rat (4) and by 71% in the guinea pig (2). A number of studies have shown previously that glucagon, after stimulation of adenylate cyclase activity, increased the intracellular level of cAMP in isolated rat hepatocytes (31), in the isolated perfused rat (39), and in guinea pig liver (2).…”

Section: Discussionmentioning

confidence: 98%

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Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Alvaro¹,

Guardia²,

Bini³

et al. 1995

J. Clin. Invest.

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To elucidate mechanisms of glucagon-induced bicarbonaterich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pH1) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pH1, significantly stimulates the Cl-/HCO3 exchange activity.The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3-exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3 exchange was individually blocked by two specific and selective inhibitors of protein kinase A, uM) and H-89 (30 ,uM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl -channel blocker, NPPB (10 pmM), showed no effect on either the basal or the glucagon-stimulated Cl-/ HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 jpM), completely blocked the glucagon stimulation of the C1-/HCO3 exchange; however, this effect was achieved through a significant inhibition of the glucagonstimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3 exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pH1 or at acid pH, values. In contrast, glucagon, at basal pH1, stimulated the Na+-HCO-symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3 exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis. (J. Clin. Invest. 1995.

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Section: Discussionmentioning

confidence: 98%

“…Moreover, glucagon, at physiological doses, induces a bicarbonate-rich choleresis in humans (1) as well as in many different animal species, including the guinea pig (2), dog (3), and rat (4). Mechanisms of glucagon choleresis are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Alvaro¹,

Guardia²,

Bini³

et al. 1995

J. Clin. Invest.

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“…31 In the liver, insulin increases bile flow in several species. [13][14][15][16]32,33 The choleretic effect of insulin is direct and not mediated by changes in the plasma levels of hormones (e.g., glucagon and somatostatin) or glucose. 15,32,34 Although the mechanism of insulin choleresis is undefined, studies showed that (1) insulin acts at the bile canaliculus since insulin-induced choleresis is associated with increased erythritol clearance 16 and (2) insulin increases the bile salt-independent fraction of bile flow but it does not alter bile salt secretion.…”

Section: Discussionmentioning

confidence: 99%

“…1,7,8 Insulin stimulates canalicular bile secretion in dogs, rats, and guinea pigs. [13][14][15] The concept that insulin stimulates canalicular bile flow by interaction with hepatocytes is supported by studies in dogs showing that insulin increases erythritol clearance. 16 No information exists regarding (1) the functional expression of insulin receptors in cholangiocytes and (2) the role and mechanism of action of insulin in the regulation of ductal secretion.…”

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confidence: 99%

Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity

et al. 2002

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Insulin stimulates canalicular bile flow by interaction with hepatocytes. Insulin regulates the function of a number of epithelia through activation and membrane translocation of Ca(2+)-dependent PKC isoforms. No information exists regarding insulin regulation of ductal bile secretion. The aim of the study was to determine the role and mechanisms of action of insulin in the regulation of cholangiocyte secretion in BDL rats. We determined the subcellular localization of insulin receptor in cholangiocytes. We measured the effect of insulin on (1) secretin-stimulated cAMP levels in cholangiocytes and duct expansion in intrahepatic bile duct units (IBDUs) in the absence or presence of BAPTA/AM, H7 or rottlerin and (2) bile flow. We evaluated (1) if insulin effects are associated with activation of PKC alpha and (2) if activation of PKC causes inhibition of secretin-stimulated cAMP levels and PKA activity. We found insulin receptors only in the apical domain of cholangiocytes. Insulin inhibited secretin-induced choleresis and secretin-stimulated cholangiocyte cAMP levels. Insulin inhibited secretin-induced secretion in IBDUs when applied at the basolateral membrane or microinjected into IBDU lumen. Insulin inhibitory effects on cholangiocyte secretion were blocked by BAPTA/AM and H7. Insulin induced activation of PKC alpha, which decreased secretin-stimulated cAMP and PKA activity. In conclusion, insulin inhibited secretin-induced ductal secretion of BDL rats through activation of PKC and inhibition of secretin-stimulated cAMP and PKA activity. In conclusion, insulin counter-regulates cholangiocyte secretory processes in the BDL model, which is characterized by cholangiocyte proliferation.

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“…9-11) was made in the early 1980s from the Institute of Physiology at Aarhus University (71)(72)(73)(74)(75)(76). The main purpose of the study was to examine the mechanism and regulation of bile acid-independent canalicular bile production.…”

Section: Mechanism and Regulation Of Hepatic Bile Productionmentioning

confidence: 99%

Bile Acids in Health and Disease

Krag

Thaysen²

1996

Scandinavian Journal of Gastroenterology

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Krag E, Thdysen EH. Bile acids in health and disease. Scand J Gastroenterol 1996;31 Suppl 216:73-81. Over the last quarter of a century Danish research on bile acids has comprised studies of their physical and chemical properties, their physiology, pathophysiology, metabolism, and kinetics, and their clinical applicability. In the beginning of the period a major contribution was made to the understanding of the factors involved in the solubility of cholesterol in bile. The growing international understanding of the potential importance of the bile acids in health and disease gave raise to a substantial Danish contribution in the 1970s and 1980s in parallel with international achievements. Emphasis was on the possible clinical implications of bile acids. Studies on physiology and pathophysiology were in focus. Patients who have had an intestinal bypass operation for obesity served as a model for obtaining new knowledge on various aspects of the properties of the bile acids. Also the analytical methods were improved. Important physiological research on the mechanisms of hepatic bile flow was conducted. An intestinal perfusion model served as a tool providing information on absorption kinetics and on transmucosal water and electrolyte movements. The gallstone disease, liver diseases, inflammatory bowel disease, fat malabsorption, and other intestinal disorders were studied. The 'idiopathic ileopathy' as a cause for bile acid malabsorption causing diarrhoea was established as a new disorder. Thus, in the time period concerned, substantial Danish contributions emerged on major and minor topics of the bile acid field. (fax: +45 35 31 39 99) The research on bile acids in health and disease performed by Danes over the past quarter of a century has resulted in more than 130 papers published in international periodicals. BILE, BILIARY LIPIDS, BILE ACIDS, AND GALLSTONES Up to the period concerned, clinical research on bile acids had been moderate. Nevertheless, a fairly substantial Danish contribution was made by the Nobel prize laureate Henrik Dam and his co-workers, who developed a gallstone model in the hamster (1) and later examined human bile as well (2). Scand J Gastroenterol Downloaded from informahealthcare.com by Nyu Medical Center on 12/14/14 For personal use only.

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The effect of glucagon, dibutyrylic cyclic AMP and insulin on bile production in the intact rat and the perfused rat liver

Cited by 34 publications

References 16 publications

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Effect of glucagon on intracellular pH regulation in isolated rat hepatocyte couplets.

Insulin inhibits secretin-induced ductal secretion by activation of PKC alpha and inhibition of PKA activity

Bile Acids in Health and Disease

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