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

Fetal rat liver cells were transformed with a temperature-sensitive A mutant (tsA255) of simian virus 40. A CLONAL CELL LINE, RLA255-4, which was temperature sensitive in the maintenance of the transformed phenotype, was isolated. This cell line expressed the transformed phenotype (rapid growth, high cell density, overgrowth of normal cells, and cloning in soft agar) at the permissive temperature (33 degrees C) and the nontransformed phenotype (slower growth, lower saturation density, decreased efficiency of overgrowth of normal cells, and lower cloning efficiency in soft agar) at the restrictive temperature (40 degrees C). The tsA255-transformed cells expressed differentiated liver functions under controllable conditions. At the permissive temperature, they produced low levels of albumin and transferrin, whereas at the restrictive temperature the transformed phenotype was lost and the production of these hepatic proteins was greatly enhanced. RLA255-4 cells contained functional receptors for glucagon, as shown by the stimulation of intracellular cyclic AMP accumulation by glucagon. The response to glucagon was dose dependent (Kact = 5 x 10(-8) M) and could be demonstrated in cells grown at both permissive and restrictive temperatures after 7 days in culture (i.e., at a cell density of approximately 4 x 10(5) cells per cm2 or higher). Addition of cortisol to the culture medium enhanced the glucagon response selectively at the restrictive temperature.
 ...
PMID:Establishment of a fetal rat liver cell line that retains differentiated liver functions. 624 62

Injury or stress generates a vigorous metabolic response designed to establish the metabolic priorities required for the repair of injured tissues. In this condition, hormones commonly found to be elevated in the plasma include glucagon, catecholamines, glucocorticoids, growth hormone, aldosterone, and antidiuretic hormone. This hormonal profile results in rapid lysis of body protein, an increased rate of fat oxidation, and water and salt conservation. Rates of gluconeogenesis and ureagenesis are accelerated and may result in significant losses in lean body mass, a process that, if allowed to progress, will adversely affect patient survival. Exogenous nutrients provided to the critically ill patient may be poorly tolerated and may result in complications. Dextrose and intravenous fat emulsions provide the major sources of parenteral, nonprotein energy. These energy sources may not be metabolized efficiently in these patients, even though energy expenditure in this condition is increased significantly. Measurement of urinary nitrogen losses yields evidence useful in assessing the patient's degree of stress. In this manner, the patient's energy and protein requirements may be estimated. Formulations of amino acids, including the branched-chain amino acids, in higher concentrations have been reported to have anticatabolic effects and may improve the maintenance of lean body mass in stressed individuals. The stressed patient is prone to metabolic complications and, therefore, requires more careful monitoring of fluid, electrolyte, and acid-base balance, as well as renal, pulmonary, and liver function. Nutritional status is difficult to assess, since negative nitrogen balance may persist and the visceral proteins such as transferrin become altered in stress and, therefore, may not respond to nutritional intervention alone. The goal of nutritional therapy is the preservation of lean body mass by the safe and efficacious provision of metabolic substrate, thus improving patient survival.
 ...
PMID:Nutritional support of the critically ill patient. 640 74

A clonal rat adult hepatocyte cell line (RALA255-10G) was shown to be temperature sensitive (ts) for growth and differentiation. Glucocorticoid was necessary to maintain the maximal levels of differentiated functions in these cells. The RALA255-10G cell line was established by transforming primary adult hepatocytes with simian virus 40 tsA255 virus that is temperature sensitive for maintenance of transformation. At the permissive temperature (33 degrees C), RALA255-10G cells showed characteristics of malignant transformation, synthesized low levels of albumin and transferrin, and contained low levels of functional receptors for glucagon. At the nonpermissive temperature (40 degrees C), these cells regain the normal differentiated phenotype, and the levels of these three hepatic functions were increased. Induction of albumin and transferrin production by RALA255-10G cells at 40 degrees C was shown to be the result of the increase in the biosynthesis of these proteins. Furthermore, the albumin and transferrin produced by these cells were immunologically and electrophoretically indistinguishable from authentic rat albumin and transferrin. Glucocorticoid, which reduced the growth rate and saturation density of RALA255-10G cells at 33 degrees C, was absolutely required by these cells to synthesize albumin at both temperatures. This hormone also enhanced transferrin production and glucagon response. Our data indicate that glucocorticoid hormone is one of the factors that maintain adult hepatocytes in a differentiated state.
 ...
PMID:Temperature-sensitive adult liver cell line dependent on glucocorticoid for differentiation. 687 37

A human colon carcinoma cell line, HC84S, was established in serum-supplemented medium from a colon tumor line T84 transplanted in nude mice. These cells also grew in a serum-free, synthetic medium supplement with insulin, glucagon, epidermal growth factor, transferrin, hydrocortisone, triiodothyronine, selenium, and ascorbic acid. HC84S cells grew 3 times faster in this medium than in serum-containing medium and formed gland-like structures closely resembling the original tumor morphologically. In serum-containing medium, the cells grew as a monolayer and did not form such structures. Primary cultures from transplantable human colon tumor lines maintained in nude mice and a primary tumor from a patient were established directly in this hormone-supplemented medium in collagen-treated plastic dishes without fibroblast overgrowth. The hormone-supplemented medium may be generally useful for the establishment of human colon carcinoma cell lines.
 ...
PMID:Hormonal control of human colon carcinoma cell growth in serum-free medium. 693 31

After trauma or sepsis, the liver undergoes a reprioritization of export protein synthesis with elevated production of some acute-phase reactants and reduced production of others. We have examined the effects of combinations of insulin and the counterregulatory hormones (dexamethasone, glucagon, and epinephrine), in the presence or absence of interleukin (IL)-6, on the production by isolated hepatocytes of the positive acute-phase proteins C-reactive protein, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, and haptoglobin, and the negative acute-phase proteins prealbumin and transferrin. The effect of IL-6 on the production of the above proteins was influenced significantly by insulin and all of the counterregulatory hormones. Significant three-way interactions as well as higher order interactions between the stress hormones and insulin were seen in the case of C-reactive protein. The results indicate that both positive and negative acute-phase proteins respond differently to insulin and the counterregulatory hormones and that the potential exists for the regulation of synthesis of individual acute-phase reactants by interaction between the cytokine network and the classical endocrine hormones.
 ...
PMID:Insulin and counterregulatory hormones influence acute-phase protein production in human hepatocytes. 754 33

Endocrine abnormalities in patients with chronic renal failure are well documented. The present study aimed to assess the influence of long-term erythropoietin (EPO) therapy on endocrine abnormalities in hemodialyzed patients. Two groups of hemodialyzed patients, each of which comprised 17 subjects, were examined. The first group was treated by EPO (EPO group) while the second one did not receive this hormone (No-EPO group). A complete biochemical and hormonal check-up was performed before and at the 3, 6, 9, and 12 month points of the study period. Normal values for the estimated parameters were obtained in appropriately selected sex- and age-matched healthy subjects. After EPO therapy, an increase of the hematocrit value from 21.8 +/- 0.9 to 32.6 +/- 0.9% was observed, which was accompanied by a significant decline of plasma ferritin and saturation of transferrin. In patients of the No-EPO group, a significant although less marked rise of the hematocrit value (21.4 +/- 0.4 to 24.2 +/- 0.6%) was also noticed. EPO therapy did not change plasma levels of electrolytes (Na, K, Ca, inorganic phosphate), osteocalcin, creatinine, glucose, and alkaline phosphatase as well as plasma concentrations of calcium-related hormones (PTH, calcitonin, 1,25[OH]2D3), vasopressin, and triiodothyronine. EPO treatment induced a significant decrease in somatotropin, prolactin, follitropin, lutropin, ACTH, cortisol, plasma renin activity, aldosterone, noradrenaline, adrenaline, dopamine, glucagon, pancreatic polypeptide, and gastrin plasma levels and an increase in plasma insulin, estradiol, testosterone, atrial natriuretic peptide, thyrotropin, and thyroxine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Function of endocrine organs in hemodialyzed patients of long-term erythropoietin therapy. 762 22

Glucagon-like peptide-1 (GLP-1) is the most potent stimulator of glucose-induced insulin secretion and its pancreatic beta-cell receptor is a member of a new subfamily of G-protein-coupled receptors which includes the receptors for vasoactive intestinal polypeptide, secretin and glucagon. Here we studied agonist-induced GLP-1 receptor internalization in receptor-transfected Chinese hamster lung fibroblasts using three different approaches. First, iodinated GLP-1 bound at 4 degrees C to transfected cells was internalized with a t 1/2 of 2-3 min following warming up of the cells to 37 degrees C. Secondly, exposure to GLP-1 induced a shift in the distribution of the receptors from plasma membrane-enriched to endosomes-enriched membrane fractions, as assessed by Western blot detection of the receptors using specific antibodies. Thirdly, continuous exposure of GLP-1 receptor-expressing cells to iodinated GLP-1 led to a linear accumulation of peptide degradation products in the medium following a lag time of 20-30 min, indicating a continuous cycling of the receptor between the plasma membrane and endosomal compartments. Potassium depletion and hypertonicity inhibited transferrin endocytosis, a process known to occur via coated pit formation, as well as GLP-1 receptor endocytosis. In contrast to GLP-1, the antagonist exendin-(9-39) did not lead to receptor endocytosis. Surface re-expression following one round of GLP-1 receptor endocytosis occurred with a half-time of about 15 min. The difference in internalization and surface re-expression rates led to a progressive redistribution of the receptor in intracellular compartments upon continuous exposure to GLP-1. Finally, endogenous GLP-1 receptors expressed by insulinoma cells were also found to be internalized upon agonist binding. Together our data demonstrate that the GLP-1 receptor is internalized upon agonist binding by a route similar to that taken by single transmembrane segment receptors. The characterization of the pathway and kinetics of GLP-1-induced receptor endocytosis will be helpful towards understanding the role of internalization and recycling in the control of signal transduction by this receptor.
 ...
PMID:Agonist-induced internalization and recycling of the glucagon-like peptide-1 receptor in transfected fibroblasts and in insulinomas. 764 46

The objective of these studies was to develop serum-free culture conditions for dissociated acini from rat submandibular glands. Acini were isolated from the submandibular glands of 42-46 d old rats and cultured on reconstituted rat tail collagen containing laminin in 1:1 Ham's F12 and Dulbecco's media, supplemented with BSA, transferrin, insulin, T3, EGF, dexamethasone, retinoic acid, carbamylcholine, and trace elements, and gassed with 50% O2. The acini became partly embedded in the collagen gel and rapidly enlarged throughout the first 22 d of culture, maintaining modest seromucous acinar differentiation, as judged morphologically and by mucin secretion. Parallel cultures then were grown under 20, 35, 50, and 65% O2, and evaluated morphologically and by DNA content. Growth and retention of seromucous acinar characteristics were best with 35% O2, but lipid accumulation and cell death were unacceptably high. A spectrum of concentrations of insulin and glucagon then were tried. With 0.05 micrograms/ml insulin, cellular growth and organization were orderly, lipid accumulations were not excessive, and moderate differentiation was retained through 15 d of culture. With more than 0.1 microgram/ml insulin added to or subtracted from the optimum, the detrimental effects recurred. Addition of sufficient glucagon counteracted the effects of both optimum and excessive concentrations of insulin. We now have achieved an orderly growth of moderately differentiated rat submandibular acini for 15 d in serum-free primary culture.
 ...
PMID:Effects of oxygen, insulin, and glucagon concentrations on rat submandibular acini in serum-free primary culture. 789 74

Most of diabetics have no symptoms and chemical analyses may be sole way to diagnose the disease itself and its complications. Chemical analyses are also important to assess the propriety of glycemic control during every possible treatment of diabetes. Some markers for long-term glycemic control other than glucose concentration may be also used as a screening methods for glucose intolerance. HbA1c is established for long term as a marker for glycemic control but still large interlaboratory variation is present. Fructosamine is measured by a simpler procedure but many deoxidizing materials in serum especially superoxide may interfere with the reaction. Glycated albumin should be more reliable than fructosamine but a standard method of measurement has not been established yet. The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary glucose excretion and may be useful as a marker of glycemic control and diagnosis of diabetes. Discrimination of Type I(IDDM) from Type II(NIDDM) in Japanese diabetic patients is sometimes very difficult and evidences of autoimmunity by anti-glutamic acid decarboxylase(GAD) antibody and of exhaustion of insulin secretion by C-peptide measurement 6min after combined infusion of 1mg of glucagon and 20ml of 50% glucose are the few methods to diagnose. Early diagnosis of diabetic complication is another important point of clinico-chemical determinations. Usually, each diabetic complication progresses in parallel. Micro-measurement of urinary transferrin is one of the most sensitive methods likewise urinary microalbumin measurement. Future measurement of advanced glycation end product (AGE) may also tell us if patients are suffering from diabetic complications or if one is suffering from diabetes or not.
 ...
PMID:[Recent progress in diagnoses of diabetes and its complications]. 856 34

The metabolic response to trauma and sepsis involves an increased loss of body proteins. Specific sites of changes of protein and amino acid metabolism have been identified. In skeletal muscle, the rate of proteolysis is accelerated greatly. The rate of protein synthesis also may be increased but not enough to match the increase in degradation. Intramuscular glutamine concentration is decreased because of increased efflux and possibly decreased de novo synthesis. In the liver, the rate of synthesis of selected proteins (i.e., albumin, transferrin, prealbumin, retinol-binding protein, and fibronectin) is decreased, whereas acute phase protein synthesis is accelerated. Tissues characterized by rapidly replicating cells, such as enterocytes, immune cells, granulation tissue, and keratinocytes, exhibit early alterations in the case of decreased protein synthesis capacity. In these tissues, glutamine use is accelerated. Increased stress hormone (cortisol and glucagon) and cytokine secretion, as well as intracellular glutamine depletion, are potential mediators of altered protein metabolism in trauma and sepsis. However, the relative importance of these factors has not been clarified. Therapy of acute protein catabolism may include the use of biosynthetic human growth hormone, possibly in combination with insulin-like growth factor-1, and the administration of metabolites at pharmacologic doses. We recently studied the effects of carnitine and alanyl-glutamine administration in severely traumatized patients. We found that both carnitine and the glutamine dipeptide restrained whole-body nitrogen loss without affecting selected indices of protein metabolism in the skeletal muscle.
 ...
PMID:Metabolic response to injury and sepsis: changes in protein metabolism. 929 Jan 10


<< Previous 1 2 3 4 5 Next >>