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)

Corticosteroids are considered to be essential stress hormones. They are secreted together with adrenocorticotropic hormone (ACTH) in response to the pulsatile secretion of corticotropin-releasing hormone from the paraventricular nucleus of the hypothalamus. Changes in pulse amplitude are responsible for the diurnal rhythm in circulating ACTH and cortisol levels. Steroid levels increase immediately after injury, pain, fever, and hypovolemia in response to the stimulation of corticotropin-releasing hormone secretion by various cytokines. The increase in steroid levels is typically proportional to the magnitude of stress, with serum cortisol values being highest in moribund patients and shortly before death. With severe and prolonged stress, steroid levels are increased for weeks to months and may be associated with hypertrophy of the adrenal cortex. Cortisol acts in concert with catecholamines to maintain the vascular tone, endothelial integrity, vascular permeability, and the distribution of total body water within the vascular compartment. It also potentiates the vasoconstrictor effects of catecholamines. Cortisol helps to stimulate lipolysis, inhibit protein synthesis, facilitate amino acid mobilization from muscle, induce the enzymes of gluconeogenesis, enhance secretion of glucagon, inhibit insulin secretion, and stimulate conversion of lactic acid to glycogen. Because of their anti-inflammatory properties, steroids have been proposed as therapeutic adjuvants in systemic inflammation and may protect the host against overshooting defense reactions by reducing the migration of leukocytes to the inflammatory sites and the incidence of neutrophil-mediated tissue injury and organ dysfunction.
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PMID:Steroids. 1238 86

Tissue injury is associated with decreased cellular immunity and enhanced metabolism. Immunodepression is thought to be counteracted by interferon (IFN)-gamma, which increases human leukocyte antigen (HLA)-DR expression. Hypermetabolism could be enhanced by IFN-gamma because cytokines induce a hypermetabolic response to stress. In healthy humans, IFN-gamma enhanced HLA-DR expression without effects on glucose and fat metabolism. In the present study, we evaluated whether IFN-gamma lacks potential harmful side effects on metabolic and endocrine pathways while maintaining its beneficial effects on the immune system under conditions in which the inflammatory response system is activated. In 13 patients scheduled for major surgery, we studied HLA-DR expression on peripheral blood monocytes before surgery and postoperatively randomized the patients into an intervention and a placebo group. Subsequently, we evaluated the effects of a single dose of IFN-gamma vs. saline on short-term monocyte activation, glucose and lipid metabolism, and glucose and lipid regulatory hormones. HLA-DR expression on monocytes was restored from postoperative levels of 54% (42-60%; median and interquartiles) to 92% (91-96%) 24 h after IFN-gamma administration but stayed low in the placebo-treated patients. IFN-gamma did not affect glucose metabolism (plasma glucose, rate of appearance and disappearance of glucose) and lipid metabolism (plasma glycerol, plasma free fatty acids, and rates of appearance and disappearance of glycerol). IFN-gamma had no effect on plasma cortisol, adrenocorticotropic hormone, growth hormone, insulin, C-peptide, glucagon, epinephrine, and norepinephrine concentrations. We conclude that IFN-gamma exerts a favorable effect on cell-mediated immunity in patients after major surgery without effects on glucose and lipid metabolism.
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PMID:Interferon-gamma increases monocyte HLA-DR expression without effects on glucose and fat metabolism in postoperative patients. 1450 92

The circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus not only controls the basal daily temporal organization of many neuroendocrine functions, but also its responsiveness. We studied the time-of-day influence on plasma changes in adrenocorticotropic hormone (ACTH), corticosterone, glucagon and leptin concentrations elicited by an insulin-induced hypoglycaemic event. Male Wistar rats were exposed to an insulin challenge at six different times during the light/dark cycle. The time-of-day of exposure markedly affected the responses of all four hormones studied. Generally, the magnitude of the different hormone responses correlated with their basal daily release pattern (i.e. the responses of ACTH and corticosterone were largest around lights off, and glucagon and leptin responses were most pronounced during the dark period). With regard to the hormones of the hypothalamic-pituitary-adrenal axis, the presently reported time-of-day dependent modulation is completely opposite to that previously reported for novelty or restraint. Therefore, these findings provide further support for the existence of at least two different neural pathways that are able to activate the hypothalamic-pituitary-adrenal axis, and provide different substrates for modulation by the biological clock. This observation warrants a thorough examination of possible functional explanations for the observed differences.
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PMID:The diurnal modulation of hormonal responses in the rat varies with different stimuli. 1463 76

The effects of anesthetic agents, commonly used in animal models, on blood glucose levels in fed and fasted rats were investigated. In fed Sprague-Dawley rats, ketamine (100 mg/kg)/xylazine (10 mg/kg) (KX) produced acute hyperglycemia (blood glucose 178.4 +/- 8.0 mg/dl) within 20 min. The baseline blood glucose levels (104.8 +/- 5.7 mg/dl) reached maximum levels (291.7 +/- 23.8 mg/dl) at 120 min. Ketamine alone did not elevate glucose levels in fed rats. Isoflurane also produced acute hyperglycemia similar to KX. Administration of pentobarbital sodium did not produce hyperglycemia in fed rats. In contrast, none of these anesthetic agents produced hyperglycemia in fasted rats. The acute hyperglycemic effect of KX in fed rats was associated with decreased plasma levels of insulin, adrenocorticotropic hormone (ACTH), and corticosterone and increased levels of glucagon and growth hormone (GH). The acute hyperglycemic response to KX was dose-dependently inhibited by the specific alpha2-adrenergic receptor antagonist yohimbine (1-4 mg/kg). KX-induced changes of glucoregulatory hormone levels such as insulin, GH, ACTH, and corticosterone were significantly altered by yohimbine, whereas the glucagon levels remained unaffected. In conclusion, the present study indicates that both KX and isoflurane produce acute hyperglycemia in fed rats. The effect of KX is mediated by modulation of the glucoregulatory hormones through stimulation of alpha2-adrenergic receptors. Pentobarbital sodium did not produce hyperglycemia in either fed or fasted rats. Based on these findings, it is suggested that caution needs to be taken when selecting anesthetic agents, and fed or fasted state of animals in studies of diabetic disease or other models where glucose and/or glucoregulatory hormone levels may influence outcome and thus interpretation. However, fed animals are of value when exploring the hyperglycemic response to anesthetic agents.
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PMID:Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models. 1624 6

We analyzed pancreatic endocrine tumors (PETs) from 200 patients for the incidence of multihormonality and entrapped islets and correlated the results with clinicopathological features. Our series included 86 cases (43%) of functioning PET and 114 cases (57%) of nonfunctioning PET. Classified according to the WHO classification, there were 32 well-differentiated benign PETs, 85 well-differentiated PETs with uncertain behavior, and 83 well-differentiated malignant PETs. All tumors were immunostained for pancreatic hormones (insulin, glucagon, somatostatin, and pancreatic polypeptide) and for additional hormones such as gastrin, vasoactive intestinal polypeptide, calcitonin, seratonin, and adrenocorticotropic hormone. Multihormonality was found in 34% of all PETs and it was a frequent finding in the tumors of the uncertain behavior (38.8%) group. Islet entrapment was found in 57 tumors (28.5%) and was significantly more frequent in PETs with uncertain and malignant behavior than benign ones (p=0.01). In 57 cases, we also investigated whether ductule entrapment accompanied islet entrapment. Of these 57 tumors, 45 (79%) tumors had accompanying ductule entrapment. Ductule entrapment did not show significant correlation with malignancy and was a more frequent finding in nonfunctioning tumors. We conclude that the incidence of multihormonality in PETs is not as high as suggested previously and islet entrapping may reflect aggressive tumor growth and may be a complementary criterion for predicting the biological behavior of PETs.
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PMID:Multihormonality and entrapment of islets in pancreatic endocrine tumors. 1641 41

The glycogen body (GB) is in the dorsal area of the lumbosacral spinal cord in birds and is composed of uniform cells characterized by high glycogen storage. The glycogen of GB cells remains unchanged in vivo by the effects of a variety of hormones such as insulin, glucagon, adrenocorticotropic hormone and by physiological conditions such as starvation. In order to investigate the latent functionability of GB cells, we observed morphological changes of glycogen body cells in a co-culture system with cerebellar neurons by light and transmission electron microscopy. Cultured GB cells were labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). The cultured neurons derived from cerebellum were co-cultured with the labeled GB cells. Under the co-culture with neurons, 2 types of GB cells were detected. One was conventional with numerous glycogen deposits in the cytoplasm and tended to make clusters. The other type of GB cells singly extended the processes attaching to the neuronal body and axons. In the axons in contact with GB cell processes, small vesicles appearing as synaptic vesicles were observed. These observations suggested that some GB cells can differentiate to an average astrocyte. The GB cells were assumed to involve the synapse formation or maturing as astrocytes in the CNS.
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PMID:Interaction between glycogen body cell and neuron: examination in co-culture system. 1708 87

Sex and the endocrine system exert a significant influence on the physiology and pathophysiology of the lacrimal gland. The purpose of this article is to briefly review the nature and magnitude of these interactions between sex, hormones and lacrimal tissue, and to address how they may relate to the pathogenesis of aqueous-deficient dry eye. Towards this end, this article has a 3-fold approach: first, to summarize the influence of androgens, estrogens, glucocorticoids, mineralocorticoids, retinoic acid, prolactin, alpha-melanocyte stimulating hormone, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, growth hormone, thyroid-stimulating hormone, arginine vasopressin, oxytocin, thyroxine, parathyroid hormone, insulin, glucagon, melatonin, human chorionic gonadotropin and cholecystokinin on the structure and function of the lacrimal gland; second, to discuss the mechanism of action of each hormone on lacrimal tissue; and third, to discuss the clinical relevance of the endocrine-lacrimal gland interrelationship, with a particular focus on each hormone's role (i.e. if relevant) in the development of aqueous-tear deficiency.
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PMID:Tearful relationships? Sex, hormones, the lacrimal gland, and aqueous-deficient dry eye. 1721 82

A carcinoid tumor was found as a solitary soft mass in the wall of the rectum adjacent to the anorectal junction in an adult Holstein cow. Microscopically, the tumor involved the submucosa and partly invaded the muscular layer. It consisted of a compact arrangement of a great number of large polygonal cells and a small number of small dark cells, some of which showed argyrophilia (Grimelius positive). Immunohistochemically, both types of tumor cells were positive for vimentin, keratin, and S-100 protein and weakly positive for neuron-specific enolase (NSE), whereas they were negative for some endocrine markers such as chromogranin A, insulin, glucagon, somatostatin, serotonin, adrenocorticotropic hormone, and calcitonin. Electron microscopy revealed membrane-bound secretory granules in the cytoplasm of some small dark cells. In such a poorly differentiated carcinoid, the morphologic characteristics of the small dark cells were strong evidence for the diagnosis. This is the first description of a poorly differentiated carcinoid developing in the rectum of a cow.
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PMID:Poorly differentiated rectal carcinoid in a cow. 1749 Oct 91

Plant cathepsin B-like cysteine protease (CBCP) plays a role in disease resistance and in protein remobilization during germination. The ability of animal cathepsin B to function as a dipeptidyl carboxypeptidase has been attributed to the presence of a dihistidine (His110-His111) motif in the occluding loop, which represents a unique structure of cathepsin B. However, a dihistidine motif is not present in the predicted sequence of the occluding loop of plant CBCP, as determined from cDNA sequence analysis, and the loop is shorter. In an effort to investigate the enzymatic properties of plant CBCP, which possesses the unusual occluding loop, we have purified CBCP from the cotyledons of daikon radish (Raphanus sativus) by chromatography through Sephacryl S-200, DEAE-cellulose, hydroxyapatite and organomercurial-Sepharose. The molecular mass of the enzyme was estimated to be 28 kDa by SDS/PAGE under reducing conditions. The best synthetic substrate for CBCP was t-butyloxycarbonyl Leu-Arg-Arg-4-methylcoumaryl 7-amide, as is the case with human cathepsin B. However, the endopeptidase activity of CBCP towards glucagon and adrenocorticotropic hormone showed broad cleavage specificity. Human cathepsin B preferentially cleaves model peptides via its dipeptidyl carboxypeptidase activity, whereas daikon CBCP displays both endopeptidase and exopeptidase activities. In addition, CBCP was found to display carboxymonopeptidase activity against the substrate o-aminobenzoyl-Phe-Arg-Phe(4-NO(2)). Daikon CBCP is less sensitive (1/7000) to CA-074 than human cathepsin B. Expression analysis of CBCP at the protein and RNA levels indicated that daikon CBCP activity in cotyledons is regulated by post-transcriptional events during germination.
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PMID:Purification and characterization of cathepsin B-like cysteine protease from cotyledons of daikon radish, Raphanus sativus. 1895 67

Sucrose intake has been shown to suppress increased adrenocorticotropic hormone (ACTH) levels in adrenalectomized rats, suggesting that increased cerebral energy supply can compensate for the loss of glucocorticoid feedback inhibition of the hypothalamo-pituitary-adrenal axis. We hypothesized that glucose infusion might acutely down-regulate increased ACTH secretion in patients with Addison disease. We studied 8 patients with primary adrenal insufficiency (Addison group) with short-term discontinuation of hydrocortisone substitution and 8 matched healthy controls in 2 randomized conditions. Subjects received either intravenous glucose infusion (0.75 g glucose per kilogram body weight for 2.5 hours) or placebo. Concentrations of ACTH, cortisol, catecholamines, growth hormone, glucagon, and insulin were measured; and cognitive functions as well as neuroglycopenic and autonomic symptoms were assessed. The ACTH concentrations were not affected by glucose infusion either in the Addison or in the control group. Likewise, concentrations of cortisol, epinephrine, norepinephrine, growth hormone, and glucagon remained unchanged in both groups. Neurocognitive performance and symptom scores were likewise not affected. Independent of glucose infusion, attention of the Addison patients was impaired in comparison with the control group. Our study in patients with Addison disease was not able to support the assumption of a compensatory effect of intravenous glucose infusion on hormonal parameters and neurocognitive symptoms in states of chronic cortisol deficiency. Further studies should examine whether different regimens of glucose administration are more effective.
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PMID:Effects of glucose infusion on neuroendocrine and cognitive parameters in Addison disease. 1970 91


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