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 observe the distribution of multiple hormones in nonsecreting islet cell tumors of the pancreas and to study their histogenesis, 9 pancreas nonsecreting islet cell tumor cases were studies using 12 kinds of antisera. The results showed that 4 cases were positive for insulin, 6 for glucagon, 1 for gastrin, 6 for somatostatin, 1 for gastrin 5 for calcitonin, 7 for neurotensin, 4 for ACTH, 3 for TSH, 5 for FSH and 2 for LH. It is therefore confirmed that these tumors synthesize and secrete peptide hormones and glycoprotein hormones. We believe that these endocrine cells originate from primitive multipotential stem cells.
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PMID:[Immunohistochemical studies of nonsecreting pancreatic islet cell tumors secreting many hormones]. 938 78

Glucagon-like peptide-1 (GLP-1), a potent regulator of glucose homeostasis, is also produced in the central nervous system, where GLP-1 has been implicated in the neuroendocrine control of hypothalamic-pituitary function, food intake, and the response to stress. The finding that intracerebroventricular GLP-1 stimulates LH, TSH, corticosterone, and vasopressin secretion in rats prompted us to assess the neuroendocrine consequences of disrupting GLP-1 signaling in mice in vivo. Male GLP-1 receptor knockout (GLP-1R-/-) mice exhibit reduced gonadal weights, and females exhibit a slight delay in the onset of puberty; however, male and female GLP-1R-/- animals reproduce successfully and respond appropriately to fluid restriction. Although adrenal weights are reduced in GLP-1R-/- mice, hypothalamic CRH gene expression and circulating levels of corticosterone, thyroid hormone, testosterone, estradiol, and progesterone are normal in the absence of GLP-1R-/- signaling. Intriguingly, GLP-1R-/- mice exhibit paradoxically increased corticosterone responses to stress as well as abnormal responses to acoustic startle that are corrected by glucocorticoid treatment. These findings suggest that although GLP-1R signaling is not essential for development and basal function of the murine hypothalamic-pituitary-adrenal axis, abrogation of GLP-1 signaling is associated with impairment of the behavioral and neuroendocrine responses to stress.
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PMID:Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling. 1065 Sep 25

Although hypopituitarism is a known complication of head injury, it may be underrecognized due to its subtle clinical manifestations. The nonspecific symptoms may be masked by and may contribute to the physical and psychological sequelae of brain trauma. This study examines the prevalence of neuroendocrine abnormalities in patients rehabilitating from traumatic brain injury. Seventy adults (mean age, 31.5 +/- 1.1 yr; range, 18--58; 46 men and 24 women) with traumatic brain injury an average of 49 +/- 8 months before the study (median, 13 months) underwent a series of standard endocrine tests, including serum levels of TSH, free T(4), insulin-like growth factor I, PRL, testosterone (males), and cosyntropin stimulation. Abnormal results of these tests were followed by dynamic tests of gonadotropin, TSH, and GH secretion. Glucagon stimulation testing in 48 subjects revealed GH deficiency (peak, <3 microg/L) in 14.6%. Free T(4) (n = 6; 8.6%), TSH (n = 7; 10%), or both (n = 2; 2.9%) were low in 21.7%, whereas 87% had both TSH and free T(4) below the midnormal level. Basal morning cortisol was below normal in 45.7% of subjects, whereas cosyntropin-stimulated levels were insufficient (peak, <500 nmol/L) in 7.1%. Hypogonadism and hyperprolactinemia were uncommon. In summary, pituitary hormone deficiencies were identified in a substantial proportion of patients with previous brain injury. GH deficiency, found in 15% by glucagon stimulation testing, may compound the physical and psychological complications of traumatic brain injury and interfere with rehabilitation.
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PMID:Prevalence of neuroendocrine dysfunction in patients recovering from traumatic brain injury. 1139 82

TRH was initially found in the hypothalamus and regulates TSH secretion. TRH is also produced by insulin-containing beta-cells. Endogenous TRH positively regulates glucagon secretion and attenuates pancreatic exocrine secretion. We have previously shown that triiodothyronine (T(3)) down-regulates pre-pro-TRH gene expression in vivo and in vitro. The present study was designed to determine the initial impact of T(3) on rat TRH gene promoter and to compare this effect with that of dexamethasone (Dex). Primary islet cells and neoplastic cells (HIT T-15 and RIN m5F) were transiently transfected with fragments of the 5'-flanking sequence of TRH fused to the luciferase reporter gene. The persistence of high TRH concentrations in fetal islets in culture, probably due to transactivating factors, allowed us to explore how T(3) and Dex regulate the TRH promoter activity in transfected cells and whether the hormone effect is dependent on the cell type considered. TRH gene promoter activity is inhibited by T(3) in primary but not neoplastic cells and stimulated by Dex in both primary and neoplastic cells of islets. These findings validate previous in vivo and in vitro studies and indicate the transcriptional impact of these hormones on TRH gene expression in the pancreatic islets.
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PMID:Differential regulation of the TRH gene promoter by triiodothyronine and dexamethasone in pancreatic islets. 1143 Nov 41

The effects of combined general anaesthesia and epidural analgesia in various endocrine and metabolic parameters were studied before, during, at the end, and 72 h after upper abdominal surgery, in an effort to further elucidate the role of epidural analgesia in the endocrine and metabolic response. 50 patients were randomly assigned into groups A and B, which received general anaesthesia alone and combined general anaesthesia and epidural analgesia, respectively. The effects of surgical stress in the plasma concentration of ACTH (P <0.001), cortisol (P <0.01), aldosterone (P <0.05), FFA (P <0.05) and glucose (P <0.01) were significantly less pronounced in the group of patients who received combined general anaesthesia and epidural analgesia. However, there were no significant differences between the two groups in regard with plasma TSH, T3, T4, glucagon or Na+ concentration. These results indicate that the combination of general anaesthesia and epidural analgesia attenuate, but does not inhibit, the endocrine and metabolic response to upper abdominal surgery.
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PMID:Epidural analgesia attenuates the systemic stress response to upper abdominal surgery: a randomized trial. 1158 7

Somatostatin (SRIF, somatotropin release inhibiting factor), discovered for its inhibitory action on growth hormone (GH) secretion from pituitary, is an abundant neuropeptide. Two forms, SRIF14 and SRIF28 exist. Recently, a second family of peptides with very similar sequences and features was described; the cortistatins (CST), CST17 and CST29 which are brain selective. The five cloned SRIF receptors (sst1-5) belong to the G-protein coupled/ heptathelical receptor family. Structural and operational features distinguish two classes of receptors; SRIF1 - sst2/sst3/sst5 (high affinity for octreotide or seglitide) and SRIF2 = sst1/sst4(very low affinitty for the aforementioned ligands). The affinity of SRIF receptors for somatostatins and cortistatins is equally high, and it is not clear whether selective receptors do exist for one or the other of the peptides. Several radiologlands label all SRIF receptors, e.g., [125]LTT-SRIF28' [l25I]CGP23996, [125]Tyr10cortistatin or [125I]Tyr11SRIF14. In contrast, [125I]Tyr3octreotide, [125I]BIM23027, [125I]MK678 or [125I]D-Trp8SRIF14 label predominantly SRIF1 sites, especially sst2 and possibly sst5 receptors. In brain, [125I]Tyr3octreotide binding equates with sst2 receptor mRNA distribution. Native SRIF2receptors can be labeled with [125I]SRIF14 in the presence of high NaCl in brain (sst1) or lung (sst4) tissue. Short cyclic or linear peptide analogs show selectivity for sst2/sst5 (octreotide, lanreotide, BIM 23027), sst1 (CH-275), sst3 (sst3-ODN-8), or sst5 receptors (BIM 23268); although claims for selectivity have not always been confirmed. Beta peptides ith affinity for SRIF receptors are also reported. The general lack of SRIF receptor antagonists is unique for peptide receptors, although CYN 154806 is a selective and potent sst2 antagonist. Nonpeptide ligands are still rare, although a number of molecules have been reported with selectivity and potency for sst1 (L 757,519), sst2 (L 779,976), sst3 (L 796,778), sst4 (NNC 26-9100, L 803,087) or sst1/sst5 receptors (L 817,018). Such molecules are essential to establish the role of SRIF receptors, e.g., sst1 in hypothalamic glutamate currents: sst2 in inhibiting release of GH, glucagon, TSH, gastric acid secretion, pain, seizures and tumor growth, and sst5 in vascular remodeling and inhibition of insulin and GH release.
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PMID:Drug design at peptide receptors: somatostatin receptor ligands. 1193 45

We have investigated the acute effects of preproglucagon derived peptides (PGDP) - glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), and exendin-4 (EX4), a GLP-1 receptor agonist, on thyrotropin (TSH) secretion in the rat. Within 120 min after subcutaneous injection, neither glucagon nor GLP-1 or GLP-2 had an effect on blood rTSH concentration in adult female rat. On the contrary, EX4 injection significantly lowered the plasma thyrotropin level. A potent inhibitory effect of EX4 administration on blood rTSH level was seen even 12 h after bolus peptide administration, whereas EX4-induced elevation in blood glucose concentration returned to normal values after 6 h of experiment. EX4 administration in doses from 0.05 to 1.00 nmol/100 g body weight resulted in very similar drop in blood rTSH levels. To check whether EX4-induced lowering in blood rTSH concentrations may be prevented by exendin-(9-39) [EX(9-39)], rats were treated with EX4 and/or EX(9-39). Both the bolus administration and the 3-day treatment with EX(9-39) notably lowered blood rTSH concentration of studied rats. Administration of EX(9-39) did not change blood rTSH response to EX4. Results of our in vivo studies are rather unexpected and raise serious questions on the specificity of EX4 and EX(9-39) action in vivo. Since both the native EX4 molecule as well as its truncated form [EX(9-39)] exerts a similar inhibitory effect on TSH secretion in the rat, it seems legitimate to suggest that this action depends only on 9-39 amino acid sequence of EX4. Moreover, obtained results suggest that both EX4 and EX(9-39)-evoked inhibition of TSH secretion in the rat is not dependent on their interaction with GLP-1 receptor only. Detailed mechanism of such action remains to be elucidated.
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PMID:Preproglucagon derived peptides and thyrotropin (TSH) secretion in the rat: robust and sustained lowering of blood TSH levels in exendin-4 injected animals. 1216 9

Oxyntomodulin (OXM) is a product of proglucagon processing in the intestine and the central nervous system. We reported that intracerebroventricular (ICV) and intranuclear administration of OXM caused an inhibition of food intake in rats (Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, and Bloom SR. Endocrinology 142: 4244-4250, 2001). In this study, we investigated the effect of twice-daily ICV administration of OXM, 1 nmol, for 7 days. A pair-fed control was included. These animals were restricted to the food intake of the OXM group but injected twice daily with saline. OXM-treated animals gained significantly less weight than either control group (day 8: OXM, 12.2 +/- 1.9 g vs. pair fed, 21.0 +/- 2.1 g; P < 0.005). OXM treatment caused a reduction in epididymal white adipose tissue (OXM, 1.13 +/- 0.03 g vs. pair fed, 1.29 +/- 0.04 g; P < 0.05) and interscapular brown adipose tissue (OXM, 0.15 +/- 0.01 g vs. pair fed, 0.18 +/- 0.01 g; P < 0.05) and increased core temperature compared with saline control, suggestive of enhanced energy expenditure. The food restriction-induced suppression in plasma TSH, seen in the pair-fed group, was prevented by OXM, potentially via increased release of hypothalamic TRH. In summary, ICV OXM causes reduced body weight gain and body adiposity following chronic administration.
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PMID:Repeated ICV administration of oxyntomodulin causes a greater reduction in body weight gain than in pair-fed rats. 1238 65

OBJECTIVE: To report a case of Persistent Hyperinsulinemic Hypoglycemia in twins which is a situation not yet reported in the literature. METHODS: Report of seizures in identical twins, from consanguineous parents, with persistent hypoglycemia as cause of the seizures. Laboratory tests, performed for etiological investigation of the hypoglycemia, included thyroid hormones (T4/TSH), insulin, cortisol, growth hormone, stimulation test with glucagon (to evaluate the insulin/glucose relation), and histopathological study of the pancreas. RESULTS: Laboratorial investigation revealed a persistent hypoglycemia with hyperinsulinism which were confirmed with the stimulation test with glucagon. The histopathological exam showed a persistence of first generation pancreatic islet, confirming the diagnosis of Persistent Hyperinsulinemic Hypoglycemia in Infancy (the new denomination of Nesidioblastosis). CONCLUSION: Although rare, this condition must be early suspected early in the evaluation of hypoglycemia of the young infant, even out of the neonatal period, specially if the parents are consanguineous. The adequate therapy must be quickly initiated in order to prevent neurological damage.
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PMID:[Persistent hyperinsulinemic hypoglycemia of infancy: case report] 1464 92

SS, a natural cyclic tetradecapeptide, is a potent suppressor of pituitary GH and TSH secretion. At least five distinct SS receptor (SSTR) subtypes have been cloned and termed SSTRs 1-5. Both SSTR2 and SSTR5 regulate human GH and TSH secretion. Recently, a novel enzymatically stable SS analog, PTR-3173 (Somatoprim), with affinity for human SSTR2, SSTR4 and SSTR5, has been identified. This cyclic heptapeptide analog suppressed rat GH in vivo with no effect on insulin and minimal effect on glucagon secretion. Using primary cultures of human fetal pituitaries (20-24-week gestation) and GH-secreting adenomas, we studied the in vitro inhibitory effects of PTR-3173 on human pituitary secretion. PTR-3173 suppressed GH release from both fetal pituitaries (maximal suppression of 54% with 10 nM) and cultures of GH-cell adenomas (35% suppression with 100 nM). Octreotide and PTR-3173 had comparable inhibitory effects on GH secretion from fetal human pituitaries. TSH was mildly suppressed by PTR-3173, whereas ACTH secretion was not affected in fetal pituitary cultures. In cultures of eight GH-secreting adenomas, octreotide was superior to PTR-3173 in suppressing GH from two adenomas, PTR-3173 was more potent in three other tumors, and three adenomas did not respond significantly to either analog. PTR-3173 suppressed PRL in several mixed GH-PRL adenomas. In conclusion, PTR-3173, a novel SS analog with a unique SSTRs binding combination, is a potent in vitro suppressor of human GH. Combining this inhibitory effect with the lack of effect on insulin secretion, it is suggested that PTR-3173 may be clinically useful for the treatment of acromegaly.
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PMID:PTR-3173 (somatoprim), a novel somatostatin analog with affinity for somatostatin receptors 2, 4 and 5 is a potent inhibitor of human GH secretion. 1563 23


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