Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Portal hypertension is characterized by a pathologic increase in portal venous pressure that leads to the formation of an extensive network of portosystemic collaterals that divert a large fraction of portal blood to the systemic circulation, bypassing the liver. Experimental models have improved understanding of the pathophysiology of portal hypertension. It is now clear that an increased vascular resistance to portal blood flow is the initial factor responsible for the increase in portal pressure. This resistance is exerted along the hepatic and portal-collateral circulation and is in part modifiable by pharmacologic agents. In a latter stage, an increased portal venous blood inflow, promoted by splanchnic vasodilation, contributes to maintenance and aggravation of portal hypertension. Humoral vasodilatory agents play an important role in the splanchnic vasodilation. Several vasodilators are likely to be involved, including glucagon, prostacyclin, endotoxins, and nitric oxide. The splanchnic vasodilation is associated with a hyperkinetic systemic circulation, with reduced arterial pressure and peripheral resistance and increased cardiac output. The splanchnic circulation is probably the vascular territory in which the vasodilation is more pronounced. Therefore, splanchnic and systemic vasodilation probably share some pathophysiologic events. An expanded plasma volume is observed in all forms of portal hypertension. Expansion of plasma volume is due to renal sodium retention, which has been shown to precede the increase in cardiac output and can be prevented or reversed by sodium restriction and spironolactone. The expanded blood volume represents another mechanism that contributes to further increases in portal pressure.
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PMID:Pathophysiology of portal hypertension. 156 69

Whether the decrease of portal venous inflow and portal pressure induced by somatostatin is related to the effects of somatostatin in inhibiting the secretion of glucagon and other vasodilatory peptides that are increased in portal hypertension was investigated in the current study. Splanchnic vascular resistance and splanchnic blood flow were determined using radioactive microspheres in rats with portal hypertension caused by partial portal vein ligation. Somatostatin infusion significantly decreased portal pressure (from 13.1 +/- 1.9 to 12.1 +/- 2.2 mm Hg; P less than 0.05). This was associated with a significant decrease in portal venous inflow caused by splanchnic vasoconstriction, as evidenced by increased splanchnic vascular resistance, and with a marked suppression of glucagon secretion. The simultaneous infusion of somatostatin and glucagon (2.8 ng/min, a dose that prevented any decrease in circulating glucagon levels) abolished all the hemodynamic effects of somatostatin. This effect seems to be specific because no hemodynamic changes were noted in portal hypertensive rats receiving only the glucagon infusion.
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PMID:Glucagon hinders the effects of somatostatin on portal hypertension. A study in rats with partial portal vein ligation. 168 27

Chronic pancreatitis is difficult to treat in patients with a nondilated duct. Patients experiencing intractable pain unresponsive to or judged untreatable by lesser procedures must decide between total pancreatectomy and resultant diabetes or a continuation of their pancreatitis. From 1977 through 1990, 26 patients underwent extensive pancreatectomy and dispersed pancreatic islet tissue autotransplantation for treatment of chronic pancreatitis pain and prophylaxis of surgical diabetes. Of these 26 patients, total (Whipple) or near-total (greater than 95%) pancreatectomy was performed in 24 patients. Of these 24 patients, pain relief could be assessed in 21 patients at 5 to 155 months (mean, 5.7 years), and 19 patients (90%) reported partial or complete remission. Of the patients who underwent total or near-total pancreatectomy, islets were injected intraportally in 22 patients and into the renal subcapsule in two patients. The latter two patients have required insulin since surgery. Of the other 22, one patient died from a complication of the pancreatectomy. Nine of the 21 evaluable recipients of intraportal islet autografts were insulin independent for at least several months after surgery. Five patients are currently insulin independent at 6 years, 4 years, 1.5 years, 9 months, and 5 months after surgery. Of the other four patients, one patient died insulin independent at 6 years, and three patients required insulin beginning 8 to 18 months after surgery. Insulin independence correlated with the number of islets recovered, which in turn correlated inversely with the degree of pancreatic fibrosis. Of our four most recent patients, three patients had mildly to moderately fibrotic glands, and higher numbers of islets were obtained. After total (Whipple) pancreatectomy, these three patients are insulin independent. A liver biopsy was performed in one patient 8 months after total pancreatectomy and islet autotransplantation; numerous clusters of islet cells staining strongly for insulin and glucagon were detected within portal triads on both wedge and needle biopsy specimens. Morbidity related to the intraportal-dispersed pancreatic islet tissue transplantation was low (no disseminated intravascular coagulation, significant portal hypertension, or hepatic dysfunction). Islet autotransplantation can be an effective and safe adjunct to extensive pancreatic resection for those patients who risk surgical diabetes for relief of their chronic pancreatitis pain.
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PMID:Autotransplantation of dispersed pancreatic islet tissue combined with total or near-total pancreatectomy for treatment of chronic pancreatitis. 185 51

Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.
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PMID:Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension. 189 7

The intestinal vascular responsiveness to arginine vasopressin was evaluated in rats with chronic portal hypertension. Male Sprague-Dawley rats were made portal hypertensive by stenosis of the portal vein. Ten to twelve days after the induction of chronic portal hypertension, the responsiveness of the small intestinal circulation to cumulative doses of vasopressin was evaluated using an isolated pump-perfused small intestinal preparation. The ED50 for maximal vasoconstriction was increased twofold in portal hypertensive rats compared with control rats. To determine if the impaired responsiveness to arginine vasopressin was related to the hyperglucagonemia of chronic portal hypertension, plasma glucagon levels were elevated in normal rats to levels previously measured in portal hypertensive rats (i.e. approximately 450 pg/mL), and the dose response studies were repeated. Glucagon significantly attenuated the responsiveness of the intestinal vasculature to vasopressin. Equipotent doses of nitroprusside also attenuated intestinal vascular responsiveness to vasopressin. The results indicate that there is a reduced vascular sensitivity to vasopressin in the intestine of portal hypertensive animals and suggest that elevations in circulating vasodilators in portal hypertensive conditions may partially explain this altered vascular responsiveness.
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PMID:Intestinal vascular sensitivity to vasopressin in portal hypertensive rats. 200 29

Effects of chronic prehepatic portal hypertension on intestinal microvascular sensitivity to norepinephrine (NE) were studied. Normal and portal hypertensive rats were anesthetized, and the intestine was prepared for in vivo microscopic observation. The preparation was transferred to a video microscope and a first-, second-, or third-order submucosal arteriole (i.e., 1A, 2A, or 3A, respectively) selected for study. Microvascular diameter and arteriolar erythrocyte velocity were measured on-line, and arteriolar blood flow was subsequently calculated as the product of velocity and vessel cross-sectional area. Once steady-state conditions were reached, the preparation was exposed to incremental doses of NE and microvessel responses were recorded. Cumulative log dose-response curves relating the change in arteriolar blood flow and vessel diameter to NE concentration were constructed for each group of arterioles and the ED50 for maximal response obtained from each dose-response relationship. NE ED50 for 1A blood flow was significantly higher in portal hypertensive rats (2.57 +/- 0.25 microM) compared with control rats (1.48 +/- 0.19 microM). Analysis of the diameter responses of 1A, 2A, and 3A indicated that the loss of vascular NE sensitivity in chronic portal hypertension was localized to the terminal submucosal arterioles (2A and 3A). No differences in the diameter response of 1A were observed between normal and portal hypertensive rats. Separate experiments were conducted to test if glucagon, a known mediator of the hyperdynamic intestinal circulation in portal hypertension, could acutely alter NE responsiveness in normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intestinal microvascular responsiveness to norepinephrine in chronic portal hypertension. 201 19

The authors assessed in 12 patients with compensated cirrhosis of the liver, portal hypertension and oesophageal varices, using a Doppler flowmeter Toshiba SAL 50A/SDL 01 under basal conditions, changes in the width, rate of blood flow and blood flow though the trunk of the portal vein before and after intravenous administration of 1 mg glucagon. The width of the trunk of the portal vein did not change significantly during assessment. A statistically significantly increased flow through the portal vein was recorded starting during the 5th minute, and it correlated with the increased velocity of the blood flow. The increased flow persisted to the 20th minute after glucagon administration. The drop of pressure in a wedged position assessed in the hepatic veins after administration of the drug was not significant, the pressure in the free hepatic vein increased insignificantly. On the whole the portohepatic gradient declined by 10.5%, the drop was not significant. Glucagon in pharmacological doses has an early onset of action even in cirrhotic subjects whereby the increased flow through the portal vein does not lead to a rise of the portohepatic gradient. Glucagon administration thus does not increase the risk of haemorrhage from oesophageal varices during acute fibroscopy of the oesophagus and stomach in patients with portal hypertension.
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PMID:[The effect of glucagon on portal hemodynamics in patients with liver cirrhosis]. 202 94

The changes of humoral substances in the blood of cirrhotic rats were studied together with their effects on portal hemodynamics at different stages during the development of cirrhosis. The profiles of humoral substances and hemodynamics in two different cirrhotic rat models were also investigated. During the development of cirrhosis, glucagon increased markedly in all stages, histamine and vasoactive intestinal polypeptide (VIP) increased in the early stage, serotonin (5-HT) and somatostatin (SS) increased in the middle and late stages. There were different patterns of humoral substances in different cirrhotic models. Glucagon was the main humoral substance elevated in CCL4 induced cirrhosis, but histamine and 5-HT were mainly elevated in the blood in thioacetamide (TAA) induced cirrhosis. The hemodynamics altered differently in different stages during the development of cirrhosis and differently in the two cirrhotic rat models. Exchange transfusions between normal and cirrhotic rats resulted in an elevation of portal flow in normal rats, but no such changes were found after exchange pressure and an increase of portal blood transfusions between normal rats. The relationship between the humoral substances and portal hemodynamics is discussed. The results of this study strongly support the hypothesis of "humoral mechanism" in the pathogenesis of portal hypertension due to cirrhosis.
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PMID:Changes of blood humoral substances in experimental cirrhosis and their effects on portal hemodynamics. 212 49

It has been suggested that protein feeding increases portal pressure in cirrhotic patients, but that carbohydrate and fat have little effect. We examined the relationship between feeding and portal pressure, using different liquid test meals (250 or 500 ml non-protein, 250 ml protein-containing, 500 ml water), in 29 alcoholic patients with cirrhosis and portal hypertension. The mean hepatic venous pressure gradient (HVPG) increased significantly 30 min after the protein meal (10% increase; p = 0.009) and returned to basal levels at 60 min. The mean HVPG also increased significantly after the non-protein meal: after 500 ml the increase was 23% at 30 min (p = 0.046) and 17% at 60 min (p = 0.12); and after 250 ml it was 15% at 30 min (p = 0.012) and 7% at 60 min (p = 0.05). Ingestion of 500 ml water caused a small, non-significant, increase in mean HVPG. Plasma glucagon levels increased significantly at 30 and 60 min after the protein meal, but did not change significantly after the non-protein meal or water. Both protein-containing and non-protein meals significantly elevate HVPG in alcoholic patients with cirrhosis and portal hypertension.
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PMID:The effect of non-protein liquid meals on the hepatic venous pressure gradient in patients with cirrhosis. 225 32

This study examined whether hyperglucagonism may promote an altered sensitivity to norepinephrine (NE) and contribute to systemic vasodilation in rats with portal hypertension due to portal vein stenosis. Three groups of male Sprague-Dawley rats were studied, portal hypertensive, normal controls, and hyperglucagonemic controls. Systemic vascular reactivity was studied by constructing dose-response curves of systemic vascular resistance (SVR) during infusions of increasing doses of NE and calculating NE ED50, the dose of NE that caused 50% of the maximal increase in SVR. Measurement of SVR was based on simultaneous measurements of arterial pressure and cardiac output (CO). Repeated measurements of CO were performed by indicator dilution curves of indocyanine green by means of a fiber-optic catheter placed in the carotid artery. Portal hypertensive rats had a decreased systemic sensitivity to NE, shown by a significant increase in NE ED50 compared with normal controls (60 +/- 8 micrograms vs. 25 +/- 3 micrograms; P less than 0.001). Glucagon levels were markedly increased in the portal hypertensive group (332 +/- 51 pg/ml vs. 176 +/- 22 pg/ml in controls; P less than 0.005). Glucagon infusion in normal rats achieved levels similar to those observed in portal hypertension (305 +/- 48 pg/ml; NS). Systemic vascular sensitivity to NE was also impaired in these hyperglucagonemic normal animals, as shown by an abnormal NE ED50 (69 +/- 16 micrograms; P less than 0.001 vs. controls) that was almost identical to that observed in portal hypertension. These results are consistent with the hypothesis that a reduced sensitivity to NE can contribute to systemic vasodilation in portal hypertension and suggest that hyperglucagonism can play a key role in its pathogenesis.
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PMID:Decreased systemic vascular sensitivity to norepinephrine in portal hypertensive rats: role of hyperglucagonism. 230 84


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