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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased extracellular potassium concentrations ([K+]o) stimulated transient increases in glucose release and 45Ca2+ washout in the perfused rat liver. Stimulated glucose release had a K0.5 of about 26 mM for [K+]o, was not desensitized by successive infusion intervals of increased [K+]o, was not affected by altering the direction of perfusion, was absolutely dependent on the presence of [Ca2+]o, and was blocked by 2 mM cobalt or 10 microM verapamil. The increase in 45Ca2+ washout resulting from increased [K+]o also was blocked by 2 mM cobalt or 10 microM verapamil. Inhibitors of vascular tone (nitroprusside, atriopeptin II), arachidonic acid metabolism (indomethacin, nordihydroguaiaretic acid), and alpha- or beta-adrenergic or muscarinic nerve stimulation/secretion (phentolamine, propranolol, atropine) were unable to inhibit the [K+]o-stimulated glucose release. ATP, ADP, and AMP concentrations in tissue freeze-clamped 2 min after the onset of infusion of 50 mM K+ were not significantly different from control tissue. Glucose release from freshly isolated suspensions or primary cultured monolayers of hepatocytes or from liver slices, all of which responded to glucagon or phenylephrine, did not respond to increased [K+]o. The results indicate that glycogenolysis stimulated by depolarizing gradients of K+ is dependent on an intact perfused vasculature and may be mediated by potential-sensitive Ca2+ channels present in the vascular endothelium of the liver.
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PMID:Potassium-mediated stimulation of hepatic glycogenolysis. 295 55

Haemodynamic effects of small and high doses of insulin during beta receptor blockade were studied in nine dogs. Beta receptor blockade was induced by 0.5 mg/kg propranolol and caused depression of cardiac performance with a significant increase in left ventricular end-diastolic pressure (LVEDP) and a significant decrease in heart rate; maximum rate of left ventricular (LV) pressure rise (LVdP/dtmax), stroke volume and cardiac output. At 15 min, after beta receptor blockade, a bolus injection of 0.5 IU/kg of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. After 30 min another bolus dose of 300 IU insulin was injected. Glucose and potassium were given to maintain physiological levels of these factors. Five minutes after a low dose of insulin there was a significant decrease in LVEDP (P less than 0.01), and a significant increase in LVdP/dtmax (P less than 0.01), in stroke volume (P less than 0.01) and in cardiac output (P less than 0.01). The other haemodynamic variables were not significantly changed. Administration of a high dose of insulin further, significantly, improved performance of the beta receptor blocked heart and caused a significant reduction in total peripheral resistance. In conclusion, insulin exerts inotropic and vasodilator effects which are dose-dependent and not related to adrenergic mechanisms.
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PMID:Haemodynamic effects of low and high doses of insulin during beta receptor blockade in dogs. 299 30

Metabolic effects of low and high doses of insulin during beta-receptor blockade were studied in eight dogs. Beta-receptor blockade was induced by 0.5 mg/kg propranolol which caused depression of heart performance. This was accompanied by a significant reduction in myocardial blood-flow and oxygen consumption. There was also a significant reduction in arterial concentrations and myocardial uptake of free fatty acids, while arterial concentrations and myocardial uptake of glucose and lactate were not significantly changed. Fifteen minutes after beta receptor blockade, an intravenous (i.v.) bolus injection of 0.5 IU/kg, of insulin, free of glucagon and calcium, was given followed by a continuous infusion of 0.5 IU/kg/h. Glucose and potassium were given to maintain constant levels of these factors. After 30 min another bolus dose of 300 IU insulin was injected. Thirty minutes after a low dose of insulin, a significant increase in heart performance was recorded at unaltered myocardial oxygen consumption. Arterial concentrations of free fatty acids were significantly reduced while levels of glucose and lactate were unchanged. Myocardial uptake of glucose increased significantly while uptake of lactate and free fatty acids was unchanged. After a high dose of insulin there was a considerable improvement in heart performance. Myocardial blood-flow and oxygen consumption were not changed, nor were there alterations in arterial concentrations and myocardial uptake of glucose, lactate and free fatty acids. It is concluded that, during beta-receptor blockade high doses of insulin improve the mechanical performance of the heart through mechanisms that are independent of insulin's effects on substrate metabolism.
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PMID:Metabolic effects of low and high doses of insulin during beta-receptor blockade in dogs. 299 31

Five cell lines have been derived from a rat transplantable islet cell tumour using two different methods. The lines differ in morphology and contain and release different amounts of insulin and glucagon (insulin content, 1-90 pmol/10(6) cells; insulin release, 6-250 pmol/10(6) cells per 24 h; glucagon content, less than 0.005-35 pmol/10(6) cells; glucagon release, less than 0.05-10 pmol/10(6) cells per 24 h). All the lines responded to the presence of the secretagogues leucine (20 mmol/l) plus theophylline (5 mmol/l) by increasing the rate of release of insulin approximately twofold. A high extracellular concentration of potassium (40 mmol/l) caused a three- to tenfold calcium-dependent increase in release of insulin and a parallel release of glucagon. Increasing the concentration of glucose from 2.8 to 16.7 mmol/l did not alter the rate of insulin release by any of the cell lines.
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PMID:Five new insulin-producing cell lines with differing secretory properties. 301 41

In a prospective randomised study in 20 insulin-dependent diabetics who had minor surgery under general anaesthesia we compared the metabolic responses to intravenous glucose-insulin-potassium infusion with those who had conventional subcutaneous insulin administration. The former treatment resulted in lower blood glucose levels both during the infusion period (p less than 0.05) as well as the entire observation period (operative, first and second postoperative days; p less than 0.01). More blood glucose values were within the intended range of 5 to 10 mmol/litre in the glucose-insulin-potassium as compared to the conventional group (48% versus 24%; p less than 0.01). The levels of lactate, 3-hydroxybutyrate, glycerol, alanine, glucagon, insulin and growth hormone did not differ between the two groups. The infusion regimen resulted in better glycaemic control both peri-and postoperatively than the conventional subcutaneous insulin regimen in insulin-dependent diabetic patients who have minor surgery.
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PMID:Insulin treatment of the insulin-dependent diabetic patient undergoing minor surgery. Continuous intravenous infusion compared with subcutaneous administration. 304 11

Perifusion of rat pancreatic islets with a physiologic, 6-mM amino acid mixture resulted in typical acute and second phase glucagon secretion over 30 min. At various intervals, islets were acutely fixed and processed for scanning electron microscopy, identification of alpha cells, and measurements of single alpha cell content of calcium (Ca), potassium (K) and sodium (Na) with energy-dispersive x-ray analysis. Biphasic glucagon secretion was attended by corresponding biphasic Ca accumulation and a reciprocal, biphasic suppression of K content and acute phase suppression of Na in alpha cells. All secretory and cellular events were preceded by an evanescent upward spike in alpha cell K at 1 min. These results indicate that alpha cell glucagon secretion in response to amino acid mixtures may be initiated by a K signal and is coupled subsequently to phasic changes in alpha cell Ca content. Fluctuations of alpha cell K and Na appear to relate inversely to Ca, suggesting that transmembrane fluxes of the three cations are interrelated.
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PMID:Fluctuations of alpha cell calcium, potassium and sodium during amino acid perifusion of rat pancreatic islets. 329 45

Non-transferrin-bound iron is efficiently cleared from serum by the liver and may be primarily responsible for the hepatic damage seen in iron-overload states. We tested the hypothesis that transport of ionic iron is driven by the negative electrical potential difference across the liver cell membrane. Extraction of 55Fe-labeled ferrous iron (1 microM) from Krebs bicarbonate buffer by the perfused rat liver was continuously monitored as the transmembrane potential difference (measured using conventional microelectrodes) was altered over the physiologic range by isosmotic ion substitution. Resting membrane potential in Krebs bicarbonate buffer was -28 +/- 1 mV. Perfusion with 1 microM ferrous iron caused a reversible 3 +/- 1 mV depolarization, and higher concentrations of iron caused even greater depolarization. Conversely, depolarization of the liver cells consistently reduced iron extraction. Replacement of sodium with potassium (70 mM) or choline (131 mM) depolarized the hepatocytes to -15 and -20 mV and decreased iron extraction by 28 and 31%, respectively. Perfusion with bicarbonate-free solutions containing tricine buffer (10 mM) reduced the membrane potential to -23 mV and reduced iron extraction by 18%. In contrast, the high basal extraction of iron (91.1 +/- 1.4%) was not further increased by substitution of nitrate for chloride (-46 mV) or infusion of glucagon (-34 mV). All effects were reversible, suggesting that perfusion with 1 microM iron produced little toxicity. These findings are consistent with an electrogenic transport mechanism for uptake of non-transferrin-bound iron that is driven by the transmembrane potential difference.
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PMID:Non-transferrin-bound iron uptake by rat liver. Role of membrane potential difference. 333 96

Since hypothermia is commonly used to lower local and general metabolism during cardiopulmonary bypass, we attempted to identify its specific effects on glucose-insulin interactions. A group of nondiabetic patients undergoing hypothermic (28 degrees C) cardiopulmonary bypass with ischemic (cold) cardiac arrest was compared to a similar group operated on under normothermic conditions with potassium cardioplegia. In the absence of exogenous dextrose administration, hypothermia blocked insulin secretion for the duration of the operation. It also inhibited insulin secretion in response to an exogenous dextrose load (e.g., the priming fluid of the cardiopulmonary bypass circuit) or a glucagon injection, but this inhibition was lifted by rewarming. Blood glucose levels, which during normothermia were mildly elevated even in the absence of dextrose administration, remained normal during the hypothermic phase of cardiopulmonary bypass. By the end of the rewarming period, however, blood glucose levels had reached the same level as observed under normothermic bypass, a fact suggesting that the cold inhibition of hepatic glucose production had been only temporary. Cold inhibition of hepatic glucose production also explains why glucose clearance after a sudden dextrose load was initially faster at low body temperature than at normal temperature. Glucose-clamp studies indicated that insulin resistance was initiated by anesthesia and surgical trauma, and further accentuated by cardiopulmonary bypass, in association with elevated levels of hormones indicative of surgical stress. Regardless of body temperature changes, the assimilation of glucose by nondiabetic subjects during and immediately after bypass called for the infusion of large doses of insulin. A comparison with diabetic subjects showed that insulin-dependent patients (type I diabetes) required no more insulin during cardiopulmonary bypass than normal subjects, whereas patients with type II diabetes exhibited a marked insulin resistance during the operation and in the immediate postoperative period.
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PMID:Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia. 351 20

The intrinsic processes involved in the initiation and arrest of seizures are not completely understood. Cortical and cerebellar inhibitory mechanisms, accumulation of metabolic products, and glial uptake of extracellular potassium (K+o), anions, and released neurotransmitters are all important processes that limit focal firing and terminate a seizure once it has been initiated. Of these, the intrinsic cortical inhibitory mechanisms--i.e., recurrent and surround inhibition--appear to be the most important. Active cation and anion transport processes are two metabolic events that have yet to be elucidated but clearly could be involved in terminating a seizure discharge. For example, without an active mechanism to transport chloride, opening of the chloride channel by the inhibitory transmitter GABA would not result in increased chloride permeability. The transient hypoxia and hypercapnia and lactic acidosis that follows a severe tonic-clonic seizure produces a mixed systemic metabolic and respiratory acidosis. In experimental animals, the hypercapnia that results is sufficient to block seizure discharges. Increasing the CO2 concentration significantly reduces the extension to flexion (E/F) ratio of mice given maximal electroshock seizures (MES) and increases the time required for 50% of the animals to recover sufficiently from a first MES to be able to have another MES. The decreased E/F ratio and the increased recovery time (RT50) are both indicative of a decrease in seizure activity. Since the extent to which CO2 is allowed to accumulate in the brain is regulated by the glial specific enzyme carbonic anhydrase (CA), it follows that the glial cell has an integral role in the mechanisms involved in arresting seizure activity. In contrast, hypoxia increased the E/F ratio and decreased the RT50, evidence that seizure activity was enhanced. Another metabolic factor affecting duration of seizure activity, susceptibility to seizures, and recovery from seizures is glucose. Recovery from seizures depends in part on an adequate supply of this energy source. An inverse correlation (R = 0.95) between RT50 and blood sugar was found when the blood sugar was altered experimentally by treatments that altered the endocrine status (pancreatectomy, treatment with alloxan, cortisol, insulin, glucagon, and dextrose). Since glial cells contain (as glycogen) the small amount of glucose present in the brain, they probably hasten the ability of the brain to recover normal function following a seizure.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of glial cation and anion transport mechanisms in etiology and arrest of seizures. 370 23

Adult rat liver slices were maintained for 20 h in a novel organ culture system with minimal loss of viability and function. Potassium and adenosine triphosphate levels were maintained at in vivo levels, following an initial recovery period (2 to 4 h), for up to 20 h. Protein synthesis and secretion were linear for 20 and 16 h, respectively. In addition, the liver slices synthesized glycogen between 4 and 12 h in culture. Finally, the liver slices were hormonally responsive during the 20 h culture period as exemplified by glucagon-stimulated glucose production. This system provides a simple and effective method for the culture and biochemical maintenance of adult rat liver for 20 h with minimal loss of biochemical function.
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PMID:Maintenance of adult rat liver slices in dynamic organ culture. 378 9


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