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)

It is important to repair or ameliorate the intestinal ischemia in critically ill patients. Recent study of our suggests the superiority of dobutamine, but not dopamine, in improving the intestinal oxygenation. In this study we examined the effects of pentoxifylline (PF), glucagon (GL) and prostaglandin E1 (PGE1) during reduced blood flow of the superior mesenteric artery (SMA) in 20 anesthetized dogs. As an index of the intestinal oxygenation, tonometrically measured intestinal intramural pH (pHi) was used. A tonometer was inserted into the midjejunum through enterotomy. The SMA blood flow was measured by a transit-time flow meter. A vascular screw clamp for blood flow reduction was placed around the origin of the SMA, proximal to the flow probe. The SMA blood flow was adjusted to 70% of baseline for three hours. After two hours of decreased blood flow, pHi dropped significantly from baseline. Then, either PF (20 mg.kg-1.min-1 over 10 min, followed by 0.1 mg.kg-1.min-1), GL (1 microgram.kg-1.min-1) or PGE1 (0.05 and 0.5 microgram.kg-1.min-1) was infused intravenously for one hour. With infusions of GL and large dose of PGE1, pHi tended to decrease further, although GL increased the cardiac output. Small dose of PGE1 had no significant effect on pHi. PF treatment showed beneficial effects not only on the cardiac output and the SMA blood flow, but also on pHi. We conclude that PF therapy may restore the intestinal microvascular blood flow. Further study of the effects of PF on tissue oxygenation and blood rheology is warranted.
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PMID:[How should we treat intestinal ischemia?--II: Effects of pentoxifylline, glucagon and prostaglandin E1]. 773 95

The effect of a thromboxane (Tx) A2 receptor antagonist, ONO 3708, on cholestasis and injury related to ischemia and subsequent reperfusion (I-R) was investigated in the dog liver by assessing changes in insulin and glucagon metabolism. The left hepatic duct was ligated for 4 weeks to create a cholestatic lobe. Sixty-minute ischemia was induced by Pringle's procedure. ONO 3708 (200 micrograms/kg/min) was initiated 60 min before induction of ischemia and continued throughout the experiment. The rate of insulin metabolism was higher in the right noncholestatic lobe than in the left cholestatic lobe. There was no significant difference in the rate of glucagon metabolism between the right and left lobes. After induction of I-R, the rate of insulin metabolism, but not glucagon metabolism, decreased. The lipid peroxide level was higher and the glutathione level was lower in the cholestatic lobe than in the noncholestatic lobe. There was no significant difference in the alpha-tocopherol level between lobes. After induction of I-R, the lipid peroxide level increased and the alpha-tocopherol level decreased. There was no change in the glutathione level. I-R accelerated the release of 6-keto-prostaglandin (PG) F1 alpha, a stable metabolite of PGI2, and of TxB2, a stable metabolite of TxA2, from the liver. After I-R, cholestasis accelerated the release of TxB2, but not 6-keto-PGF1 alpha. I-R also increased the TxB2/6-keto-PGF1 alpha ratio. ONO 3708 reduced these metabolic changes in the cholestasis and after I-R. These findings suggest that ONO 3708 protects liver function, especially in the cholestatic lobe, from I-R-related injury by reducing peroxidation of lipids and the TxA2/PGI2 ratio, which predicts cellular damage, and by increasing levels of alpha-tocopherol and glutathione.
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PMID:Thromboxane A2 receptor antagonist (ONO 3708) protects from liver damage induced by cholestasis and ischemia-reperfusion. 778 41

This report describes high performance liquid chromatographic analysis of transplanted pancreatic islets. A reversed phase ODS column made it possible to measure rat insulin I, II, rat C-peptide I, II and glucagon simultaneously in isolated rat islets without using radioisotopes. Freshly isolated islets contained 118.0 +/- 9.7 ng (mean +/- SE, n = 6) insulin and 3.01 +/- 0.60 ng glucagon per islet. The insulin I/II ratio was 1.22 +/- 0.03. Isolated islets were then cultured in vitro or transplanted into mice under the renal capsule. Transplantation induced mild hypoglycemia in the recipients. The graft mean survival time was 7.2 +/- 0.4 days (n = 5). Both cultured (n = 7) and transplanted (n = 6) islets showed similar alterations of polypeptide hormones on day 4. Insulin decreased to one third and glucagon remained unchanged. The insulin I/II ratio increased twofold. In conclusion, it was suggested that the general fate of isolated islets was caused by ischemia and denervation. Relatively, ischemia may not damage alpha cells but may damage beta cells because alpha cells are peripherally located. Denervation may release beta cells from a resting state under neural tonic inhibition. Mild hypoglycemia and an increased insulin I/II ratio were related to the accelerated insulin synthesis in the isolated islets.
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PMID:High performance liquid chromatographic analysis of polypeptide hormones in transplanted rat islets. 788 34

Effects of prostaglandin (PG) E1 on ischemia-reperfusion (I-R) injury to the pancreas was evaluated using isolated in vivo perfused dog pancreas. Pancreatic endocrine and exocrine functions were stimulated with 10(-12) M cholecystokinin octapeptide (CCK-8). This amount of CCK-8 promoted production of insulin, glucagon, PGI2, and thromboxane (Tx) A2 in the pancreas. Sixty minutes of ischemia and subsequent reperfusion induced damage to pancreatic ductular, acinar, and beta cells. Intra-arterial administration of PGE1 at a dose of 0.5 microgram/kg/min throughout the experiment prevented the I-R injury, reducing plasma lipid peroxides, and elevating PGI2 without changing TxA2 in the pancreas. PGE1 thus appears to protect pancreatic function from I-R injury both by depressing the effect of free-radicals and by decreasing TxA2/PGI2 which predicts cell injury.
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PMID:Prostaglandin E1 protects dog pancreas from ischemia-reperfusion injury. 802 58

Functional recovery following ischemia and reperfusion in the isolated working rat heart perfused with glucose (11 mM) was examined in relation to pre- and postischemic levels of ATP, glycogen, glucose 6-phosphate, and the lactate-to-pyruvate ratio. The following variables were studied: feeding and fasting in vivo, addition of L-lactate (10 mM), dl-beta-hydroxybutyrate (10 mM), glucagon (0.01 and 1 micrograms/ml), and a 15-min anoxic perfusion before ischemia in vitro. Recovery was assessed as the percentage of preischemic power. Good correlation was found between functional recovery and the postischemic content of glycogen. Glycogen depletion by anoxia or glucagon before ischemia impaired recovery. There was no relationship among lactate produced, or the lactate-to-pyruvate ratio, and recovery. The addition of lactate or beta-hydroxybutyrate to hearts from fed rats increased the content of glycogen and glucose 6-phosphate, whereas addition of lactate, but not beta-hydroxybutyrate, improved recovery. There was a linear relationship between glycogen content and glucose 6-phosphate levels. In conclusion, the degree of return of oxidative metabolism and of net glycogen resynthesis reflects postischemic recovery of function. The results also suggest a role for anaplerosis of the citric acid cycle as an additional determinant of postischemic recovery.
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PMID:Metabolic recovery of isolated working rat heart after brief global ischemia. 806 97

Studies were carried out to investigate the effects of prostaglandin E1 (PGE1) pretreatment on normothermic liver ischemia. Mixed-breed dogs were divided into three groups: a control group, a group with induced liver ischemia, and a group pretreated with PGE1 followed by induced liver ischemia. Liver ischemia was induced by the Pringle procedure for 60 min. PGE1 was administered intravenously to some dogs at a dose of 0.5 microgram/kg/min for 30 min prior to the Pringle procedure. Sham operations were performed without induction of liver ischemia in control animals. Insulin, glucagon, and glucose metabolic clearance rates were examined before and after the Pringle procedure in the control and experimental groups. Insulin and glucose metabolic clearance rates decreased 5 min after declamping in the ischemic group, while the glucagon metabolism was not affected, and lipid peroxide production increased. In contrast, hepatic insulin metabolism improved, and lipid peroxide production normalized in the ischemic group which was pretreated with PGE1. This study suggests that PGE1 prevents hepatic metabolic disturbances due to warm ischemia and subsequent reperfusion.
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PMID:Prostaglandin E1 protects liver from ischemic damage. 807 86

Glucagon is a potent mesenteric vasodilator, inotrope, and stimulant of intestinal metabolism that enhances survival when given during reperfusion after intestinal ischemia. However, the mechanism of improved survival is unclear and may be due to systemic hemodynamic effects rather than intestinal metabolic changes. We examined the effects of glucagon on intestinal energy metabolism during reperfusion after intestinal ischemia. Sprague-Dawley rats were subjected to 50 min intestinal ischemia by clamping the superior mesenteric artery. All received 10 ml/kg.hr 5% glucose in normal saline for 3 hr. One group (n = 17) received 1.6 micrograms/kg.min glucagon for 2 hr beginning at reperfusion. Control rats (n = 10) received only vehicle. Jejunal biopsies preischemia, end ischemia, 10, 20, 45, 80 min, and 24 hr after reperfusion were analyzed for ATP, ADP, and AMP. ATP decreased more than 60% with ischemia and recovered substantially in all animals by 10 min postischemia. ATP recovered steadily in control rats and by 24 hr was not distinguishable from baseline. In contrast, in glucagon-treated rats, ATP decreased at 20 and 45 min during reperfusion, but recovered incompletely by 24 hr after ischemia. Energy charge (EC = ([ATP] + 1/2[ADP]) divided by ([ATP] + [ADP] + [AMP])) decreased during ischemia but recovered immediately after reperfusion in both groups, implying that energy was available, energy metabolic enzyme systems were at least partially intact, and immediate recovery was not limited by available substrate and blood flow. However, energy charge decreased slightly during glucagon infusion, suggesting increased utilization of energy or some derangement of energy metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon effect on postischemic recovery of intestinal energy metabolism. 812 Nov 67

Pancreatic graft procurement, preservation, and transplantation surgery may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascular capillaries. Thus, the amount of alpha-, beta-, and pancreatic polypeptide (PP) cell products released into the vascular space of the recipient immediately after graft reperfusion may reflect islet cell injury. To test this hypothesis, we assessed glucagon, PP, C-peptide, and insulin levels in a prospective study of 22 consecutive renal-pancreatic transplantations. Transplantation-related parameters were used to account for differences in hormone release. Five grafts were preserved using Euro-Collins preservation fluid and 17 grafts were preserved using University of Wisconsin solution (UW). The first sign of a reinstalled physiological axis was the decrease of the blood glucose concentration after a median duration of 40 min (range 5-90 min) and the association of the recipient's ambient blood glucose levels with insulin release between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia time (rs = 0.73, P < 0.001, n = 21). An immediate and marked increase in plasma levels of glucagon (from 180 +/- 18 to 585 +/- 99 ng/L, mean +/- SEM), PP (from 57 +/- 8 to 122 +/- 13 pmol/L), C-peptide (from < 0.06 +/- 0.02 to 5.43 +/- 0.63 nmol/L), and insulin (from 0.15 +/- 0.21 to 2.05 +/- 0.26 nmol/L) was observed. C-peptide release correlated with glucagon (r = 0.76, P < 0.001) and PP (r = 0.60, P < 0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postoperative period in 15 UW-preserved allografts. The diameter of the pancreatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morphological graft changes reflected by the pancreatic head diameter (r = 0.58, P = 0.02). In a stepwise multiple regression analysis, cold ischemia time was a significant factor for the release of PP (r2 = 0.18, P = 0.049) and C-peptide (r2 = 0.35, P = 0.004). We suggest that peroperative hormone release reflects endocrine tissue damage. Furthermore, cold ischemia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.
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PMID:Islet cell hormone release immediately after human pancreatic transplantation. A marker of tissue damage associated with cold ischemia. 824 11

The effects of glucagon on blood flow and high-energy phosphates in control and in rat livers damaged by ischemia were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Normal livers and livers which had been made ischemic for 20, 40, and 60 min followed by 60 min of reperfusion were studied. Ischemia led to a loss in adenosine triphosphate (ATP) within 30 min. Reperfusion after 20 min of ischemia led to complete recovery of ATP. 60 min of reperfusion after 40 or 60 min of ischemia led to only a 76% and 48% recovery of ATP, respectively. Glucagon, at doses up to 2.5 mg/kg body weight, caused no changes in the inorganic phosphate (P(i)) to ATP ratio in normal livers as measured by 31P-NMR spectroscopy. In livers which had been made ischemic for 20, 40, or 60 min, glucagon caused an increase in the P(i)/ATP ratio of 18%, 40%, and 40%, respectively. 19F-NMR detection of the washout of trifluoromethane from liver was used to measure blood flow. Glucagon-stimulated flow in the normal liver in a dose-dependent manner, with 2.5 mg glucagon/kg body weight leading to a 95% increase in flow. Ischemia for 20, 40, and 60 min followed by 60 min of reperfusion led to hepatic blood flows which were 63%, 68%, and 58% lower than control liver. In reperfused livers, blood flow after glucagon-stimulation was reduced to 56%, 43%, and 48% of control glucagon-stimulated flow after 20, 40, and 60 min of ischemia. These results indicate that ischemia followed by reperfusion leads to decreases in hepatic blood flow prior to alterations in ATP and the response of the liver to glucagon is altered in the reperfused liver.
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PMID:Response of normal and reperfused livers to glucagon stimulation: NMR detection of blood flow and high-energy phosphates. 845 8

Potent vasoconstrictors such as angiotensin II and vasopressin have been implicated as mediators of persistent vasoconstriction after reversible superior mesenteric artery (SMA) occlusion. Neither captopril (CAP), an angiotensin-converting enzyme (ACE) inhibitor, nor papaverine (PAP), a vasodilator, has proven effective in reversing this vasoconstriction when employed singly. The present study examined the combined effect of these agents in reducing mortality in a murine model of acute mesenteric ischemia. The SMAs of 106 adult male Sprague-Dawley rats were totally occluded for 85 minutes. Test agents were given intravenously at reperfusion over a 90-minute period. Survival rates were assessed at 48 hours. CAP was given as a single bolus (0.3 mg/kg) and PAP (0.5 mg/kg/h) as an infusion. Aortic and SMA blood flows were measured pretreatment and posttreatment in a separate group of 19 animals treated with CAP and PAP as single agents. chi 2 analysis and analysis of variance were used to test differences with p < or = 0.05 accepted as significant. PAP alone as an adjunct resulted in a significant increase in 48-hour survival (57% versus 19%, p < or = 0.005). PAP in combination with CAP produced the best outcome in this model (87% versus 19%, p < or = 0.005). Aortic blood flow decreased, whereas SMA blood flow increased after treatment both with CAP and with PAP, but not significantly. The combination of an intravenously administered vasodilator with either glucagon or an ACE inhibitor was the most effective adjunctive therapy in this mesenteric ischemia model. There was no evidence that an inotropic effect, rather than SMA vasodilation, was the responsible mechanism of action.
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PMID:Adjunctive vasodilator therapy in the treatment of murine ischemia. 850 68


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