Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated. Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose. An intraislet abnormality of opioid peptides action and/or secretion may play a role in the disturbances of insulin secretion in patients with type-2 diabetes mellitus.
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PMID:Beta-endorphin infusion restores acute insulin responses to glucose in type-2 diabetes mellitus. 295 94

The effect of human beta-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, less than 25) and obese (body mass index, greater than 29.5) groups. In lean subjects, infusion of 0.5 mg/h beta-endorphin caused significant increases in peripheral plasma glucose and glucagon levels, but no change in plasma insulin. In obese subjects, there was an immediate marked increase in both plasma insulin and glucagon concentrations during the beta-endorphin infusion, but the plasma glucose response was lower than that of lean subjects. In lean diabetic patients, beta-endorphin produced significant simultaneous increments in both insulin and glucagon concentrations and significantly decreased plasma glucose levels. These hormonal responses to beta-endorphin were amplified in the obese diabetic patients. There was a significant correlation (r = 0.61; P less than 0.01) between fasting plasma glucose levels and the integrated insulin area in response to beta-endorphin. The infusion of a lower dose of beta-endorphin (0.05 mg/h) in diabetic patients produced similar increments in both insulin and glucagon levels and also decreased plasma glucose concentration. These results indicate that beta-endorphin may have important glucoregulatory effects in man depending on the dose administered, the presence of obesity, and the prevailing plasma glucose concentration.
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PMID:Hyperglycemia and obesity as determinants of glucose, insulin, and glucagon responses to beta-endorphin in human diabetes mellitus. 295 63

beta-Endorphin appears to have effects on hepatic glucose production in vivo. In order to determine whether beta-endorphin modulates glucose production directly, the effects of beta-endorphin on isolated rat hepatocytes were investigated. This permitted isolation of the effects of beta-endorphin from hormonal and/or neuronal influences. A significant dose-related stimulatory effect of glucagon (10(-10) to 10(-6) mol/L) on both hepatic glucose production and glycogen phosphorylase a activity was demonstrated. No effect of either physiologic (10(-11) to 10(-9) mol/L) or supraphysiologic (10(-6) mol/L) concentrations of beta-endorphin on these parameters, under basal or glucagon-stimulated conditions, could be detected. These results suggest that reported in vivo effects of beta-endorphin to inhibit hepatic glucose production were either indirect or centrally mediated.
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PMID:Lack of effect of beta-endorphin on basal or glucagon-stimulated hepatic glucose production in vitro. 295 64

Naloxone, an opiate antagonist, was given as an intravenous bolus (5 mg) in both lean and obese healthy subjects. In lean people, there was a slight trend for insulin and C-peptide concentrations to decrease below baseline values with no glucose change. Obese subjects showed an exaggerated suppression of insulin and C-peptide and a slight decrease of glucose. Glucagon was suppressed in both groups. An infusion of human beta-endorphin (0.05 mg/h) produced only minor changes in plasma glucose, insulin, glucagon, and C-peptide concentrations in lean subjects, but caused marked increments in obese. Glucagon rose in both groups, but its response was greater in obese subjects. A ten-day treatment with naloxone (1.2 mg twice a day) did not change the metabolic and hormonal responses to an oral glucose load (75 g) in lean but significantly inhibited the insulin and C-peptide responses to glucose in obese people. These results suggest that an increased opiate drive to the pancreatic beta-cell and an increased responsiveness of insulin to beta-endorphin are present in human obesity.
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PMID:Sensitivity to beta-endorphin as a cause of human obesity. 295 73

The effects of an i.v. infusion of synthetic human beta-endorphin on the hormonal, metabolic and cardiovascular responses to surgery were investigated in female patients undergoing pelvic surgery. A beta-endorphin infusion (2 micrograms/kg as a bolus at induction of anaesthesia + 10 micrograms/kg/h for the first hour of surgery) increased plasma beta-endorphin immunoreactivity to values at least 100-fold greater than those seen during surgery in a control group of patients. In spite of this massive increase the only significant findings were a transient augmentation of the expected hyperglycaemic response and increased plasma glucagon values. There were no significant changes in ACTH, GH, insulin and cortisol secretion, in blood concentrations of lactate or glycerol, or in cardiovascular variables. Complete dissociation between plasma and cerebrospinal fluid concentrations of beta-endorphin was found even when plasma values exceeded 10,000 pmol/l in the presence of anaesthesia and surgery. These results show that the increase in circulating beta-endorphin immunoreactivity associated with clinical stress states are unlikely to modulate the associated hormonal, metabolic and cardiovascular changes.
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PMID:Beta-endorphin infusion fails to modulate the hormonal and metabolic response to surgery. 295 7

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Altered metabolic and hormonal responses to epinephrine and beta-endorphin in human obesity. 296

This study evaluated the effect of human beta-endorphin on pancreatic hormone levels and their responses to nutrient challenges in normal subjects. Infusion of 0.5 mg/h beta-endorphin caused a significant rise in plasma glucose concentrations preceded by a significant increase in peripheral glucagon levels. No changes occurred in the plasma concentrations of insulin and C-peptide. Acute insulin and C-peptide responses to intravenous pulses of different glucose amounts (0.33 g/kg and 5 g) and arginine (3 g) were significantly reduced by beta-endorphin infusion (P less than .01). This effect was associated with a significant reduction of the glucose disappearance rates, suggesting that the inhibition of insulin was of biological relevance. beta-Endorphin also inhibited glucose suppression of glucagon levels and augmented the glucagon response to arginine. To verify whether the modification of prestimulus glucose level could be important in these hormonal responses to beta-endorphin, basal plasma glucose concentrations were raised by a primed (0.5 g/kg) continuous (20 mg kg-1.min-1) glucose infusion. After stabilization of plasma glucose levels (350 +/- 34 mg/dl, t = 120 min), beta-endorphin infusion caused an immediate and marked increase in plasma insulin level (peak response 61 +/- 9 microU/ml, P less than .01), which remained elevated even after the discontinuation of opioid infusion. Moreover, the acute insulin response to a glucose pulse (0.33 g/kg i.v.) given during beta-endorphin infusion during hyperglycemia was significantly higher than the response obtained during euglycemia (171 +/- 32 vs. 41 +/- 7 microU/ml, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-endorphin-induced inhibition and stimulation of insulin secretion in normal humans is glucose dependent. 297 Apr 11

Neuroendocrine (NE) neoplasms of the human bronchopulmonary tract were examined by electron microscopy, immunocytochemistry, and gel electrophoresis of cytoskeletal proteins from microdissected tissue samples. All samples (carcinoids, well-differentiated NE carcinoma, NE carcinomas of intermediate type, NE carcinomas of the small cell type) contained significant numbers of cells that immunostained for one or more of the following neuroendocrine markers tested: bombesin, calcitonin, ACTH, leu-enkephalin, gastrin, serotonin, somatostatin, alpha-melanocyte-stimulating hormone, vasoactive intestinal peptide, glucagon, insulin, substance P, and neuron-specific enolase. Electron microscopy revealed typical NE cell features, including variable abundant and frequently heterogeneous neurosecretory granules. Tumor cells contained filaments specifically stained with different conventional and monoclonal antibodies to cytokeratins and displayed punctate plasma membrane staining with antibodies to desmoplakins, in agreement with the electron microscopic demonstration of tonofilament bundles and desmosomes. Immunocytochemistry for NE markers and cytoskeletal proteins on consecutive sections revealed both cytokeratins and neuroendocrine substances in single cells. Using gel electrophoresis of cytoskeletal proteins of tissue regions extracted with high salt buffer and detergent, we could detect, in the tumors tested, appreciable amounts of cytokeratin polypeptides 8, 18, and 19, i.e., major cytokeratins also found in certain other lung carcinomas such as adenocarcinomas. Tumor cells were not significantly stained with antibodies to other intermediate filament proteins such as vimentin, desmin, glial filament protein, and neurofilament protein. The results show that NE substances can be synthesized in cells containing a typical epithelial cytoskeleton, i.e., cytokeratin filaments and desmosomes. These findings support the notion of an epithelial character of these tumors and appear in contrast with recent reports that neurofilaments are the only type of intermediate filaments present in carcinoids and other pulmonary NE tumors. These observations may have important implications for the histogenesis of NE carcinomas and for diagnostic pathology.
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PMID:Coexpression of neuroendocrine markers and epithelial cytoskeletal proteins in bronchopulmonary neuroendocrine neoplasms. 298 72

The effect of endotoxin (lipopolysaccharide from E. coli) on isolated adrenocortical cells was examined. Lipopolysaccharide decreased the ACTH-induced steroidogenesis. This effect was shown by all corticotropin concentrations studied, and the longer the incubation time, the higher the effect produced. The rate of decrease of ACTH-induced steroidogenesis was dependent on the concentration of lipopolysaccharide in the medium. Binding of [125I]ACTH to adrenocortical cells was modified by lipopolysaccharide; this modification was related to a decrease of the ACTH-induced steroidogenesis. This effect supports the hypothesis of a direct interaction between lipopolysaccharide and the cell membrane with a concomitant distortion of the cell surface affecting the ACTH receptor sites of their environment. [14C]Lipopolysaccharide binds to isolated adrenocortical cells. Binding specificity was investigated by competitive experiments in the presence of various types of endotoxins, polypeptide hormones and proteins. Unlabelled lipopolysaccharide from the same bacterial strain and isolated under identical conditions than the labelled lipopolysaccharide exerted the strongest inhibitory activity. Unlabelled lipopolysaccharide of various strains different from that originating the labelled lipopolysaccharide exerted the less displacement. It would imply a certain kind of specificity but the decrease in the binding of lipopolysaccharide produced by ACTH and glucagon suggests the existence of non-specific interactions between lipopolysaccharide and cell membrane.
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PMID:Influence of E. coli endotoxin on ACTH induced adrenal cell steroidogenesis. 298 73

Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human pancreatic tumor GH-releasing factor. 298 23


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