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)

The present study was performed to determine whether alterations in fuel reserves or energy substrate utilization might explain the performance decrements that occur in bacterial infections. Male Fisher-Dunning rats were studied at 24, 48, and 72 h after inoculation with Streptococcus pneumoniae. Rats were either sedentary or subjected to a 2-h swimming session at these three time points (N = 10 in each group). A more than 60% reduction (P less than 0.01) in performance capacity was observed on day 3 of infection compared with that in noninfected controls. This infection in the rat is characterized by fever (P less than 0.01), depression of plasma zinc (P less than 0.01) and free fatty acid (FFA) levels (P less than 0.01), inhibition of the two- to threefold increase in fasting ketonemia, and a decreased (NS) insulin:glucagon ratio, indicating a catabolic state. Glycogen stores were reduced in the heart (47%), liver (43%), and skeletal muscles (39%) but not in the carcass. Superimposed exercise resulted in a further reduction but not depletion of liver, muscle, and carcass glycogen stores, a less pronounced lactic acid accumulation, and a lower oxygen debt. However, plasma FFA and ketone body levels were still maintained or even elevated, suggesting that fat is supplied as fuel during swimming exercise in this infection. Thus, results indicate that unavailability of energy substrates or lactacidosis is not limiting for performance capacity during this severe infection.
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PMID:Metabolic responses to swimming exercise in Streptococcus pneumoniae infected rats. 205 98

1. The inflow of Mn2+ across the plasma membranes of isolated hepatocytes was monitored by measuring the quenching of the fluorescence of intracellular quin2, by atomic absorption spectroscopy and by the uptake of 54Mn2+. The inflow of other divalent metal ions was measured using quin2. 2. Under ionic conditions which resembled those present in the cytoplasmic space, Mn2+, Zn2+, Co2+, Ni2+ and Cd2+ each quenched the fluorescence of a solution of Ca2(+)-quin2. 3. The addition of Mn2+, Zn2+, Co2+, Ni2+ or Cd2+ to cells loaded with quin2 caused a time-dependent decrease in the fluorescence of intracellular quin2. Plots of the rate of decrease in fluorescence as a function of the concentration of Mn2+ reached a plateau at 100 microM-Mn2+. 4. The rate of decrease in fluorescence induced by Mn2+ was stimulated by 20% in the presence of vasopressin. The effect of vasopressin was completely inhibited by 200 microM-verapamil. Adrenaline, angiotensin II and glucagon also stimulated the rate of decrease in the fluorescence of intracellular quin2 induced by Mn2+. 5. The rate of decrease in fluorescence induced by Zn2+, Co2+, Ni2+ or Cd2+ was stimulated by between 20 and 190% in the presence of vasopressin or angiotensin II. 6. The rates of uptake of Mn2+ measured by atomic absorption spectroscopy or by using 54Mn2+ were inhibited by about 20% by 1.3 mM-Ca2+o and stimulated by 30% by vasopressin. 7. Plots of Mn2+ uptake, measured by atomic absorption spectroscopy or with 54Mn2+, as a function of the extracellular concentration of Mn2+ were biphasic over the range 0.05-1.0 mM added Mn2+ and did not reach a plateau at 1.0 mM-Mn2+. 8. It is concluded that (i) hepatocytes possess both a basal and a receptor-activated divalent cation inflow system, each of which has a broad specificity for metal ions, and (ii) the receptor-activated divalent cation inflow system is the receptor-operated Ca2+ channel.
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PMID:The liver cell plasma membrane Ca2+ inflow systems exhibit a broad specificity for divalent metal ions. 216 60

The absorption of zinc is increased when the dietary zinc supply is low. This is caused by increased intestinal transport and reduced secretion of endogenous zinc into the intestine. Kinetic analysis of zinc transport, based on data from either the isolated perfused intestine or brush border membrane vesicles, demonstrates uptake velocity is increased homeostatically by a carrier-mediated phase of transport in response to low dietary zinc. Zinc within intestinal cells binds to high molecular weight proteins and metallothionein. Expression of the metallothionein gene is altered by zinc status and the protein appears to have a function in intestinal cells. Zinc transport across the basolateral membrane is also carrier-mediated and may be ATP-driven. Newly absorbed zinc is transported via albumin, first to the liver and then is redistributed to other tissues, particularly muscle and bone which provide the greatest reserves. Plasma zinc levels remain relatively constant except during periods of dietary zinc depletion and acute responses to stress, infection or inflammation where they are depressed. Experiments with intact rats and isolated rat liver parenchymal cells have shown that hepatic zinc turnover is rapid. Stimulation of liver cells by glucocorticoids, glucagon, epinephrine, cAMP or interleukin-1-like factors alters uptake/exchange kinetics such that there is a net accumulation of cellular zinc. Metallothionein gene expression is enhanced by these hormonal signals, and a considerable portion of the newly accumulated zinc is accounted for as that associated with this zinc-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Toward a molecular understanding of zinc metabolism. 242 May 2

Regulation of metallothionein synthesis and concomitant changes in the kinetics of zinc metabolism are influenced by dibutyryl cAMP, epinephrine, glucagon and dexamethasone in both intact rats and isolated rat liver parenchymal cells. Liver metallothionein levels were elevated many fold and were directly related to the transient hypozincemia produced following administration of these hormones or Bt2cAMP. Incubation of monolayer cultures of liver cells with these agents caused changes in both rapidly taken up 65Zn2+ and slow 65Zn2+ exchange; and increased metallothionein levels up to 7 fold. Using a 32P-labeled oligonucleotide, corresponding to a 21 base sequence of the metallothionein gene as a hybridization probe, metallothionein mRNA levels were found to be increased by each hormone and cAMP in isolated liver cells and intact rats. This indicates metallothionein gene expression is regulated by cAMP in addition to metals and glucocorticoids. Free radical damage to isolated liver cells caused by t-butylhydroperoxide or 3-methylindole increased malondialdehyde production which could be reduced by addition of Zn2+ to the culture medium. This suggests zinc uptake influenced the extent of lipid peroxidation. Spin-trapping techniques using electron spin resonance showed zinc also reduced free radical formation by the isolated hepatocytes. The concentration of metallothionein in liver cells seems to be related to cellular functions of zinc and coordinately regulated by glucagon through changes in cAMP levels and glucocorticoids.
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PMID:Regulation of liver zinc metabolism and metallothionein by cAMP, glucagon and glucocorticoids and suppression of free radicals by zinc. 282 65

Catecholamines can induce rat hepatic zinc thionein to high levels via alpha 1- and beta 2-adrenoceptors. Polypeptide hormones (glucagon and angiotensin II) are also inducers, but only to the moderate levels attained by glucocorticoids (dexamethasone). Turpentine induced inflammation stimulates the synthesis of ZnMT, but this process is not mediated by catecholamines. Phorbol esters, which are tumor promoters, can stimulate protein kinase C. Angiotensin II and alpha 1-agonists activate protein kinase C via diacylglycerol release from phosphatidylinositol-4,5-diphosphate. Phorbol esters can also stimulate the synthesis of rat hepatic zinc thionein, implicating protein kinase C activation in this induction. The multihormonal modulation of metallothionein gene activation has become increasingly more complex.
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PMID:The involvement of catecholamines and polypeptide hormones in the multihormonal modulation of rat hepatic zinc thionein levels. 282 66

A long-acting somatostatin analog, SMS 201-995, is now available to treat the hormonal manifestations of islet cell tumors. We report its use in a patient with a metastatic glucagonoma refractory to conventional therapy. This patient, who was severely disabled by the rash of necrolytic migratory erythema and brittle diabetes mellitus, allowed us to evaluate the therapeutic efficacy of SMS 201-995 and to gain insight into the origin of the rash. SMS 201-995 was administered subcutaneously (.05 mg twice a day). The rash improved markedly within 48 hours and was completely resolved within 1 week of treatment. Insulin requirements decreased from 90 U/day to zero during the first week of treatment. Corresponding to improvement in clinical symptoms circulating glucagon levels showed a marked decrease. There was no substantial change in plasma or urinary levels of zinc or in plasma amino acid levels. When SMS 201-995 was stopped, the rash recurred within 36 hours and it improved within 48 hours of readministration. The rash and diabetes have remained well controlled during 8 months of therapy but no change in tumor size has been seen on CT scan. The rapid changes in the rash related to the administration of SMS 201-995 indicate that the pathogenesis of necrolytic migratory erythema is probably due to circulating hyperglucagonemia or some other hormonal substance produced by the tumor.
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PMID:Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. 287

The glucagonoma syndrome is characterized by a necrolytic migratory erythematous rash, angular stomatitis, painful glossitis, a normochromic normocytic anemia, mild diabetes mellitus, weight loss, a tendency to thrombosis, and neuropsychiatric disturbances. The diagnosis is made by finding a high plasma glucagon concentration in the absence of any other cause, such as renal failure or severe stress. A pancreatic alpha-cell tumor can be identified and stained by immunocytochemistry with glucagon antibodies. Optimal treatment is surgical removal, but approximately 50 percent of the tumors have metastasized by the time of diagnosis. Since the tumor is slow-growing, remission can be obtained by hepatic artery embolization to shrink hepatic secondaries or by shrinkage, in about 10 percent of patients, with the combination chemotherapeutic regimen of 5-fluorouracil and streptozotocin. The rash frequently responds to administration of zinc, a high-protein diet, and control of the diabetes with insulin. Alongside the alpha cell in the islets of Langerhans is the D-cell, which produces somatostatin and may well act physiologically as a paracrine inhibitor of glucagon release. A newly developed, long-acting somatostatin analogue, SMS 201-995, which the patient can self-administer as a subcutaneous injection, has proven effective in suppressing glucagon secretion from glucagonomas and, in some cases, causing remission of clinical symptoms.
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PMID:Glucagonoma syndrome. 288 77

A 63 year old man presented with features of the glucagonoma syndrome, that is thromboembolic disease, weight loss, raised sedimentation rate, diabetes mellitus, hypoproteinaemia and reduced plasma amino acid levels, but without necrolytic migratory erythema. The plasma glucagon level was raised and the tumour was demonstrated by abdominal CT scan. Immunofluorescent studies of the resected tumour confirmed the diagnosis. The normal tissue zinc status supports the view that necrolytic migratory erythema is related to zinc deficiency.
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PMID:Glucagonoma without cutaneous manifestations. 299 32

Regulation of zinc metabolism by dibutyryl cAMP, glucagon, and epinephrine was examined in rats fed adequate amounts of zinc. Dibutyryl cAMP, epinephrine, and glucagon each produced an increase in liver metallothionein levels by 10 h after they were first administered. The increase in liver metallothionein was inversely related to the serum zinc concentration. Treatment with dexamethasone, a glucocorticoid, accentuated these effects to some extent. Both metallothionein I and II were induced by dibutyryl cAMP and glucagon. Levels of metallothionein mRNA in total liver RNA extracts were measured by dot blot hybridization using a synthetic 21-base oligonucleotide complimentary to the 5' region of both the metallothionein I and II genes. Individual administration of dibutyryl cAMP, glucagon, and epinephrine increased the number of metallothionein mRNA molecules per cell by up to fourfold. The data suggest that glucagon and epinephrine are primary regulators of metallothionein gene expression acting at least in part via cAMP. In adrenalectomized rats, glucagon, dibutyryl cAMP, and epinephrine had a less potent effect in terms of metallothionein induction and depression of serum zinc concentrations. These effects were largely restored when dexamethasone was also given. Collectively these data suggest that changes in zinc metabolism associated with acute stress involve coordinate regulation mediated by many factors, including glucocorticoids and cAMP.
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PMID:Coordinate regulation of zinc metabolism and metallothionein gene expression in rats. 302 99

Rats weighing 220 g were injected sc with zinc protamin glucagon 20 micrograms once daily (recurrent hyperglucagonemia) and zinc protamin glucagon 60 micrograms three times daily (chronic hyperglucagonemia); the controls received the vehicle three times daily. In the first group blood glucagon rose to above 200 ng/liter for 5 h every day; in the second group it constantly stayed above 600 ng/liter. After both 2 (n = 5) and 14 (n = 5) days treatment the control total blood alpha-amino-nitrogen (AAN) concentration was 4.3 +/- 0.1 mmol/liter, and the urea nitrogen synthesis rate was 4.9 +/- 0.4 mumol/(min.100 g BW) (mean +/- SEM) in controls. In recurrent hyperglucagonemic rats, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 3.6 +/- 0.2 mmol/liter (P less than 0.05 vs. control) and urea nitrogen synthesis rate 4.5 +/- 0.8 mumol/(min.100 g BW). In chronic hyperglucagonemic, treated for both 2 (n = 5) and 14 (n = 5) days, total AAN was 2.2 +/- 0.1 mmol/liter (P less than 0.05 vs. control) and UNSR 7.9 +/- 0.8 mumol/(min.100g BW) (P less than 0.05 vs. control). The urea excretion was identical in controls and during recurrent hyperglucagonemia, but it was increased by 50% during chronic hyperglucagonemia. Food intake was the same in all groups. N Balances decreased from 10 mmol/24 h to 5 mmol/24 h (P less than 0.05) by chronic hyperglucagonemia. The total organ N content did not change by recurrent hyperglucagonemia, but in chronic hyperglucagonemia it decreased to 65-85% (P less than 0.01) in carcass, intestines, liver, and kidneys. In conclusion chronic but not recurrent hyperglucagonemia increases the rate of urea synthesis and decreases the blood amino acid concentration. This is suggested to be a reason for the loss of N from organs by chronic hyperglucagonemia.
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PMID:Loss of nitrogen from organs in rats induced by exogenous glucagon. 304 48


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