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)

In summary, the vitamin pantothenic acid is an integral part of the acylation carriers, CoA and acyl carrier protein (ACP). The vitamin is readily available from diverse dietary sources, a fact which is underscored by the difficulty encountered in attempting to induce pantothenate deficiency. Although pantothenic acid deficiency has not been linked with any particular disease, deficiency of the vitamin results in generalized malaise clinically. In view of the fact that pantothenate is required for the synthesis of CoA, it is surprising that tissue CoA levels are not altered in pantothenate deficiency. This suggests that the cell is equipped to conserve its pantothenate content, possibly by a recycling mechanism for utilizing pantothenate obtained from degradation of pantothenate-containing molecules. Although the steps involved in the conversion of pantothenate to CoA have been characterized, much remains to be done to understand the regulation of CoA synthesis. In particular, in view of what is known about the in vitro regulation of pantothenate kinase, it is surprising that the enzyme is active in vivo, since factors that are known to inhibit the enzyme are present in excess of the concentrations known to inhibit the enzyme. Thus, other physiological regulatory factors (which are largely unknown) must counteract the effects of these inhibitors, since the pantothenate-to-CoA conversion is operative in vivo. Another step in the biosynthetic pathway that may be rate limiting is the conversion of 4'-phosphopantetheine (4'-PP) to dephospho-CoA, a step catalyzed by 4'-phosphopantetheine adenylyl-transferase. In mammalian systems, this step may occur in the mitochondria or in the cytosol. The teleological significance of these two pathways remains to be established, particularly since mitochondria are capable of transporting CoA from the cytosol. Altered homeostasis of CoA has been observed in diverse disease states including starvation, diabetes, alcoholism, Reye syndrome (RS), medium-chain acyl CoA dehydrogenase deficiency, vitamin B12 deficiency, and certain tumors. Hormones, such as glucocorticoids, insulin, and glucagon, as well as drugs, such as clofibrate, also affect tissue CoA levels. It is not known whether the abnormal metabolism observed in these conditions is the result of altered CoA metabolism or whether CoA levels change in response to hormonal or nonhormonal perturbations brought about in these conditions. In other words, a cause-effect relation remains to be elucidated. It is also not known whether the altered CoA metabolism (be it cause or result of abnormal metabolism) can be implicated in the manifestations of a disease. Besides CoA, pantothenic acid is also an integral part of the ACP molecule.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pantothenic acid in health and disease. 174 61

Mild hyperglycemia was induced in normal rats by oral administration of both diazoxide and D-glucose. After 48 hours of such a treatment, the insulin and glucagon secretory responses of the perfused pancreas to alpha- and beta-D-glucose (3.3 mM) were examined in the presence of 10.0 mM L-leucine. The output of insulin, but not that of glucagon, and the perfusion pressure were higher in treated than control rats. The alpha-anomer of D-glucose was a more potent insulin secretagogue than beta-D-glucose in both control and treated rats. However, the alpha/beta ratio in insulin output was twice higher in control than treated rats. By analogy with other experimental models of diabetes, the attenuation in the anomeric difference of glucose-stimulated insulin output in the treated rats could reflect an altered secretory response to alpha- rather than beta-D-glucose. These findings suggest that hyperglycemia provokes, as a function of its severity and duration, first attenuation and then suppression, if not inversion, of the anomeric preference for alpha-D-glucose in insulin release. They are also compatible with the hypothesis that the anomeric malaise, associated with B-cell glucotoxicity, is caused by a progressive accumulation of glycogen in this cell.
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PMID:Attenuated anomeric difference of glucose-induced insulin release in the perfused pancreas of diazoxide-treated rats. 191 34

Groups of male Sprague-Dawley rats were predominantly fed either a high-fat or a high-carbohydrate (CHO) diet. For designated 2-day periods, their diets were switched. After baseline measurements of food and water intake, the rats were made diabetic by injections of either 40 or 46-50 mg/kg streptozotocin. Food and water intake gradually increased over a 15-day period for rats on the CHO diet. Whenever the diets were switched, many of the rats showed large changes in food and fluid intake. Body weight showed a gradual decline, but the rats retained half of the dissectable abdominal body fat at sacrifice. Measurements of plasma glucose, insulin and glucagon proved that the rats were diabetic. The changes in average food intake were reasonably consistent with the "utilizable fuel" theory for the control of food intake assuming that the CHO component of each diet was non-utilizable. The distribution of the fat/CHO utilizable fuel ratio in both experiments was flat and non-normal showing that some rats ate as much of the high fat diet as the high CHO diet. Other rats tended to avoid the high fat to an extent that was greater than predicted by the theory, suggesting that the fat diet may have caused malaise. Thus, the individual rat data did not provide strong support for the "utilizable fuel" theory.
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PMID:Large changes in food intake in diabetic rats fed high-fat and low-fat diets. 354 30

A 29-year-old nullipara was admitted at 31 weeks' gestation because of toxemia. She noted gradually polyuria, severe thirst, malaise, nausea and anorexia. A water-deprivation test and administration of aqueous vasopressin confirmed the diagnosis of nephrogenic diabetes insipidus. At 33 weeks' gestation, blood chemistry studies revealed moderately elevated transaminase levels and hyperuricemia. Male twins were delivered by vacuum extraction at 35 weeks' gestation. After delivery, she became drousy and icterus appeared. Acute hepatic failure with marked hyperuricemia was diagnosed. She was treated with glucose solution with glucagon and soluble insulin, branched chain amino acids, gabexate mesilate, lactulose and famotidine. Her consciousness cleared rapidly and all laboratory data became normal by 15 days postpartum. The urine volume was about 5 liters per day from the first to sixth postpartum day. The diuresis decreased after the eighth postpartum day. Rare pregnancy complicated by transient nephrogenic diabetes insipidus and acute hepatic failure is discussed.
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PMID:Transient nephrogenic diabetes insipidus associated with acute hepatic failure in pregnancy. 365 42

Stress-induced diabetic ketoacidosis is characterized by an elevation in stress hormone concentration. Whether metabolic decompensation induces or results from the secretion of stress hormones has not been examined. Our study examined the temporal relationship between the onset of stress (pyrogen-induced shaking chills and fever); the elevation in stress hormone concentation; and the rise in plasma glucose, ketone bodies, and nonesterified fatty acid concentration. Insulin deficiency, which may itself induce stress hormone secretion, was prevented by the continuous infusion of insulin (0.01 U/kg.h). Pyrogen administration induced malaise and fever in all diabetic volunteers and the rapid endogenous secretion of all stress hormones. The rise in plasma GH, catecholamines, and cortisol preceded the rise in plasma nonesterified fatty acid and ketone body concentrations by at least 30 min. The rise in plasma glucagon concentration preceded the rise in plasma glucose concentration by at lease 1 h. Thus, these studies support a primary role for stress hormones in initiating metabolic decompensation in stressed diabetic man.
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PMID:The temporal relationship between endogenously secreted stress hormones and metabolic decompensation in diabetic man. 735 Jan 76

The clinical investigations carried out in a 58 years woman complaining of malaise led to the discovery of an hypoglycaemia resulting from a secreting pancreatic insulinoma. In addition, a chronic pancreatitis, an endocrine hyperplasia (possible nesidioblastosis) and a villous adenomatosis of the pancreatic duct were diagnosed on two biopsies. The immunohistological tests performed on the insulinoma showed insulin, calcitonin and gastrin labelled cells. Electron microscopy displayed numerous neurosecretory granules. The peritumoral endocrine hyperplasia contained intermingled B, A and D cells respectively labelled by insulin, glucagon and somatostatin. Following the operation, the patient recovered without recurrence of the hypoglycaemia (three year follow-up). Factors which may explain such a rare pathological association are discussed.
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PMID:[Pancreatic insulinoma, adenomatosis of the Wirsung's duct and chronic pancreatitis. Apropos of a case]. 813 87

Glucagon-like peptide-1 (7-36) amide (GLP-1) is processed from proglucagon in the distal ileum as well as in the CNS. In the periphery, GLP-1 acts as an incretin factor and profoundly inhibits upper gastrointestinal motility ('ileal brake'), the latter presumably involving the CNS. Within the CNS, GLP-1 has a satiating effect, since administration of GLP-1 into the third cerebral ventricle reduces short-term food intake (and meal size), while administration of GLP-1 antagonists have the opposite effect. In addition, activation of GLP-1 receptors in certain brain regions elicits strong taste aversions. Similarities between toxin- and GLP-1-induced neuronal activity in the CNS (brain stem) suggest a role for central GLP-1 receptors in relaying interoceptive stress. Thus, regionally distinct GLP-1 receptor populations in the CNS may be involved in satiety or malaise. It is argued that the satiating and aversive aspects of GLP-1 serve homeostatic and nonhomeostatic functions with respect to maintenance of nutrient balance.
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PMID:Glucagon-like peptide-1 (7-36) amide: a central regulator of satiety and interoceptive stress. 1065 18

The pre-proglucagon derived peptides, glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are both involved in a wide variety of peripheral functions, such as glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Pre-proglucagon is also found in the brainstem in a small population of nerve cells in the nucleus of the solitary tract (NTS) that process the pre-propeptide as in the gut to yield GLP-1 and GLP-2. GLP-1 containing nerve fibres and the GLP-1 receptor are found predominantly in hypothalamic midline nuclei. GLP-1 given centrally to naive rats results in a marked induction of c-Fos protein in the supraoptic nucleus, paraventricular nucleus of the hypothalamus (PVN) and central nucleus of the amygdala, but only a moderate increase in the arcuate nucleus. The pattern of c-Fos activation is compatible with the appetite suppressing effects of GLP-1. This anorectic effect of GLP-1 appears to be mediated by the PVN, as direct injections of GLP-1 into this nucleus cause anorexia without concomitant taste aversion, suggesting a specific action upon neuronal circuits involved in the regulation of feeding. Recent experiments have also shown that GLP-1 is implicated in mediating signals from the gastrointestinal tract pertaining to discomfort and malaise. The distribution of the co-localised peptide, GLP-2, displays a perfect overlap with GLP-1 in the CNS with the highest concentration in the diffuse ventral part of the dorsomedial nucleus (DMHv). In contrast to the widely distributed GLP-1 receptor mRNA, GLP-2 receptor mRNA is exclusively expressed in the compact part of the DMH (DMHc). Interestingly, the DMHc is also the only nucleus responding to central administration of GLP-2 with a significant increase in the number of c-Fos positive cells. When injected into the lateral ventricle, GLP-2 has a marked inhibitory effect on feeding. The effect of GLP-2 on feeding is both behaviourally and pharmacologically specific. Future experiments will elucidate whether or not GLP-1 and GLP-2 are involved in the long-term or short-term regulation of feeding behaviour and hence have an impact on bodyweight.
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PMID:Glucagon-like peptide containing pathways in the regulation of feeding behaviour. 1184 Feb 14

About 15% of tumors of Langerhans, islets do not cause any hormone induced syndrome although they sintetise and secrete one or more regulatory peptides. These tumors are most frequently localised in the head and tail of the pancreas. They are usually greater then 5 cm. In diameter and present with pain, jaundice, palpable mass and malaise, rarely with variceal bleeding due to compression of the splenic vein. About 50% of the tumors present with symptoms caused by metastases. We present a 51 year old women in whom during the investigation for paraumbilical pain, predominantly on the left side a tumor of the tail of the pancreas was discovered and subsequently surgically removed. Standard histology showed a neuroendocrine tumor. Immunohistochemistry showed generalised immunoreactivity with antibodies against chromographin A, neuron specific enolasa and glucagon in more then 95% of cells. Somatostatatin was coexpressed in more then 5% of cells, PP in rare scattered cells. No reactivity was found for the other hormone markers. Ten years after surgery the patient has no signs of tumor recurrency.
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PMID:[Non-functioning tumor of the islets of Langerhans]. 1258 89

The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures-ventral tegmental area and nucleus accumbens-without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.
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PMID:The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors. 2249 36


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