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)

Glucagon was infused through the porta or through the left renal artery in dogs. Another group of dogs were infused with glomerulopressin through the left renal artery. It was observed that glucagon when infused through the portal vein enhanced the glomerulopressin production and the glomerular filtration rate (GFR). When glucagon was infused intrarenally it did not alter GRF but it had a direct tubular action decreasing sodium reabsorption in the proximal tubule. Glomerulopressin infused intrarenally increased GRF and potassium excretion. The results suggest that the increase in GFR was due to increase in glomerulopressin activity. There are three reasons for this statement: a) GRF increased when glomerulopressin activity was high, but not when there was a low activity, 5) intrarenally infused glomerulopressin produced a very significant change in the GFR of the infused kidney, while the GRF of the contralateral kidney remained unchanged and c) intrarenally administered glucagon had no effect on GFR.
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PMID:Effect of glucagon and glomerulopressin on the renal function of the dog. 45 30

1. The primordial GRF may have arisen quite early in evolutionary history, at or prior to (i.e. should immunoreactivity data be confirmed in invertebrates) the appearance of jawed vertebrates (Gnathostomates). A common evolutionary pathway using gene duplication may have been utilized to generate the GRF super-family of peptides. As most members of this peptide superfamily are produced in the gastrointestinal tract, the question is posed whether the GRF may have similar origins. 2. It is suggested that the GRF superfamily has two major branches: a) GRF; PRP/PACAP; VIP/PHI; secretin and b) Glucagon/GLP-1/GLP-2. GIP is likely to be a member of the glucagon branch. The two branches may be attributable to gene duplication encoding an ancestral molecule. These gene duplications are likely to have occurred prior to the evolution of vertebrates (conservatively 400-500 million years ago, and possibly 1 billion years ago). It is probable that peptides homologous to GRF, VIP and glucagon will be isolated from invertebrates. These invertebrate sequences will shed further light upon the evolution of this peptide superfamily. 3. Throughout the GRF superfamily, amphiphilic alpha-helical secondary structures represent preferred bioactive conformations. It is assumed that stable, ordered secondary structures conferring enhanced ligand-receptor interactions were conserved due to selective pressures. 4. It is well documented that hypothalamic GRF stimulates adenohypophyseal GH secretion in a variety of species. Thus far, the physiological effects of GRF have been attributed thus to the elevation of GH, and possibly also IGF-I. Recent data suggests a more liberal view; that GRF may also have direct actions in fetal/placental development, reproduction and immune function. Furthermore these direct effects may be mediated via GRF from either hypothalamic or extrahypothalamic (e.g. placenta, testes, ovary, leukocyte) sources. In conclusion, a great wealth of information has accumulated since the discovery of GRF. Examination of the GRF peptide superfamily from an evolutionary perspective has revealed new insights into the synthesis, processing, degradation, conformation and activities of these molecules. Knowledge obtained from these evolutionary comparisons has also become particularly useful in contemporary peptide drug design, which may be liberally viewed as a form of 'artificial evolution' (i.e. the selective pressure being clinical/veterinary requirements for more potent, long-acting GRF analogs).
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PMID:Evolution of the growth hormone-releasing factor (GRF) family of peptides. 129 Sep 54

Patients with type 1 diabetes mellitus (IDDM) show augmented GH secretion, which is implicated in the pathogenesis of microvascular complications. On the other hand, it is well known that beta-adrenergic receptors have inhibitory influence on GH secretion, likely via stimulation of hypothalamic somatostatin. Since the possibility of pharmacological suppression of GH secretion would be of value in IDDM, we investigated the effect of salbutamol (SAL, 4 mg orally at -60 min) on the GH response to GHRH (1 micrograms/kg iv at 0 min) in 6 well-controlled (mean HbA1c +/- SEM: 7.3 +/- 0.5%) patients with IDDM. Salbutamol was able to inhibit basal GH levels (p < 0.05) as well as to abolish the GHRH-induced GH rise. After SAL administration, a significant (p < 0.05) reduction of glucagon levels was also found. Our data show that the enhancement of beta 2 adrenergic activity by oral therapeutical doses of SAL inhibits basal and GHRH-stimulated GH secretion in patients with IDDM.
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PMID:Inhibition by salbutamol of GHRH-induced GH release in type 1 diabetes mellitus. 133 41

Two hundred and forty-one cases of isolated ACTH deficiency have been reported in Japan since 1969. Pituitary hormone responsiveness to stimulation tests before and after hydrocortisone supplementation was investigated in these cases. Plasma ACTH level showed no or little change in response to lysine vasopressin, metyrapone, CRF or insulin-induced hypoglycemia in 97.3-100% of the cases. Serum GH level changed little or not at all in response to GRF, insulin-induced hypoglycemia, glucagon, 1-dopa and arginine in 26.9, 29.3, 40.0, 50.0 and 56.1%, respectively. Serum TSH and prolactin (PRL) levels showed hyperresponse to TRH in 34.7 and 35.6%, respectively. After hydrocortisone therapy, GH secretion was more responsive than before therapy in 78.9% of the cases. After supplementation, TSH level was less responsive to TRH stimulation than before therapy in 59.3% of the cases. After hydrocortisone supplementation, TSH response to TRH decreased in 75% of ACTH-deficient patients without primary hypothyroidism but did not decrease in more than half of those with primary hypothyroidism. TSH response to TRH decreased after supplementation in 76.5% of the patients with TSH hyperresponsiveness before therapy, and increased after therapy in 66.7% of those with normal TSH responses before therapy. After supplementation, PRL response to TRH was less than that before therapy in 43.5% of ACTH--deficient patients, and greater than that before therapy in 30.4%. PRL response to TRH decreased after therapy in 66.7% of the patients with PRL hyperresponsiveness before therapy, and increased in 63.6% of those with normal PRL response before therapy. Primary hypothyroidism and Hashimoto's thyroiditis were complicated in 21.6 and 11.6%, respectively, of the 241 patients with isolated ACTH deficiency. In patients who had TSH hyperresponsiveness and/or high basal TSH levels and PRL hyperresponsiveness and/or high basal PRL levels, primary hypothyroidism was complicated in 58.4 and 42.3%, respectively. Hashimoto's thyroiditis was complicated in 29.8 and 20.5%, respectively, of these patients. Pituitary cell antibody (PCA) was detected in 36.6% of ACTH-deficient patients who were examined. Pituitary cell surface antibody (PCSA) to AtT-20 cells and GH3 cells was detected in 50.0 and 28.0% of the examined cases, respectively. The prevalence of PCA and PCSA did not differ between TSH-hyperresponsive patients and those with normal TSH basal levels and response, whereas PCA and PCSA were significantly more prevalent in PRL-hyperresponsive patients than in those with normal PRL levels and response. An empty sella was found in 30.2% of the examined case.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hyperresponsiveness of TSH and prolactin and impaired responsiveness of GH in Japanese patients with isolated ACTH deficiency]. 133 97

Effects of growth hormone-releasing factor (GRF) and intake on arterial concentrations and net visceral metabolism of hormones were measured in six growing Hereford x Angus steers using a split-plot design with 4-wk injection periods within 8-wk intake periods. Steers were fed a 75% concentrate diet at two intakes and were injected s.c. twice daily with saline or GRF (10 micrograms/kg of BW). Arterial concentrations of growth hormone (GH) were measured on d 1 and d 8 to 10 of injections. Eleven measurements, obtained at 30-min intervals, of arterial concentration and net flux of hormones across portal-drained viscera (PDV) and liver were obtained on d 8 to 10 of injections (six hourly measurements were used for insulin-like growth factor-I [IGF-I] and somatostatin). The area under the GH curve and average and peak GH concentrations were increased (P less than .01) by GRF and were greater (P less than .10) at low than at high intake. Liver removal of GH was not affected by GRF or intake. Arterial IGF-I concentration was increased (P less than .05) by GRF and not affected by intake. Treatments did not affect IGF-I flux across the liver. Arterial insulin concentration was greater (P less than .05) at high than at low intake, in part because of greater (P less than .01) PDV release. Increased (P less than .10) arterial insulin concentration in GRF-treated steers was not attributable to significant changes in PDV or liver net flux. Arterial glucagon concentration was greater (P less than .01) at high than at low intake, in part because of greater (P less than .05) PDV glucagon release and decreased (P less than .10) liver extraction ratio. Effects of intake on arterial concentration of insulin and glucagon were in part due to changes in visceral metabolism, but GRF did not affect PDV or liver hormone metabolism.
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PMID:Effects of growth hormone-releasing factor and feed intake on energy metabolism in growing beef steers: net hormone metabolism by portal-drained viscera and liver. 134 45

Thirty-eight gestating sows were either immunized against somatostatin (SRIF) and/or injected with growth hormone-releasing factor (GRF). Treatment effects on carcass composition and resistance of newborn piglets to a 60-hour fast were investigated. Protein content of carcasses at birth was increased in piglets of sows receiving GRF or immunized against SRIF, however, when sows received both treatments there was a reduction in carcass protein content (p = 0.01). Other carcass components were unaltered by treatments, and none of the treatments affected metabolic or endocrine profiles of piglets at birth. Concentrations of GH, IGF-I (p less than 0.01), glucagon and cortisol (p less than 0.05) increased linearly with duration of fast, whereas glucose values decreased. Resistance to fasting was unaltered in piglets from any treatment thereby suggesting that exogenous GRF and/or SRIF immunization of sows during gestation are unlikely to improve survival of newborn piglets.
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PMID:Carcass composition and resistance to fasting in neonatal piglets born of sows immunized against somatostatin and/or receiving growth hormone-releasing factor injections during gestation. 134 59

A 42-year-old woman with a family history of multiple endocrine neoplasia type 1 (MEN 1) presented with symptomatic hypoglycaemia and peptic ulceration. Investigation revealed an insulinoma, hyperparathyroidism, hypercalcitoninaemia with a positive pentagastrin stimulation test, acromegaly due to a GRF-oma, hyperprolactinaemia and normal serum gastrin levels. Five pancreatic tumours were removed at laparotomy and immunostaining was positive for insulin, calcitonin, somatostatin and glucagon. Post-operatively she developed elevated serum gastrin levels and gross peptic ulceration, despite H2-blockers, and died of gastro-intestinal haemorrhage suggesting that removal of the somatostatinoma may have allowed increased gastrin secretion from a gastrinoma. This case emphasizes the importance of measuring a wide variety of tumour marker peptides in MEN 1 and suggests that caution is required in interpretation of the pentagastrin stimulation test in such cases. Patients with MEN 1 and known peptic ulceration may require perioperative omeprazole treatment even if serum gastrin levels are normal.
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PMID:A case of multiple endocrine neoplasia: hyperparathyroidism, insulinoma, GRF-oma, hypercalcitoninaemia and intractable peptic ulceration. 135 65

Previous studies have demonstrated that glucagon-superfamily peptides stimulate insulin release from the pancreatic islets in a glucose dependent manner. In this study we have carried out a structure-activity study of their insulinotropic activity using a rat pancreas perfusion with 5.5 mM glucose concentration. The following peptides were examined: glucagon-like peptide-1(7-36)amide (tGLP-1), glucagon, gastric inhibitory peptide (GIP), peptide having an amino-terminal histidine and carboxy-terminal isoleucine amide (PHI), vasoactive intestinal polypeptide (VIP), growth hormone releasing factor(1-29)amide (GRF), GRF(1-27)amide and synthetic hybrid-peptides of PHI-GRF, PHI(1-11)-GRF(12-27) and PHI(1-20)-GRF(21-27). Their potencies were evaluated as: tGLP-1 = GIP > glucagon > PHI = VIP > PHI(1-20)-GRF(21-27) > PHI(1-11)-GRF(12-27) >> GRF(1-29) = GRF(1-27). It is clear that 0.1 nM tGLP-1 stimulated insulin release, whereas 1 microM GRF(1-29) did not. These results indicate that 1) in addition to N-terminal amino acid (histidine or tyrosine), position 4 (glycine), position 9 (aspartic acid) and position 11 (serine) in the amino acid sequence are important for their insulinotropic activity, 2) not only the N-terminal portion but also the C-terminal portion of these peptides contribute to their insulinotropic activity.
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PMID:Comparison of the insulinotropic activity of glucagon-superfamily peptides in rat pancreas perfusion. 146 9

A growth hormone-releasing factor (GRF)-like peptide was isolated from the hypothalamus of common carp, Cyprinus carpio, by acid extraction, gel filtration chromatography, immunoaffinity chromatography using antiserum directed against rat GRF, and multiple steps of HPLC using octadecyl columns. Based on Edman degradation and peptide mapping, this teleost GRF was established to be a 45-residue peptide with the following primary structure: His-Ala-Asp-Gly-Met-Phe-Asn-Lys-Ala-Tyr-Arg-Lys-Ala-Leu-Gly-Gln-Leu-Ser- Ala-Arg - Lys-Tyr-Leu-His-Thr-Leu-Met-Ala-Lys-Arg-Val-Gly-Gly-Gly-Ser-Met-Ile-Glu- Asp-Asp-Asn-Glu-Pro-Leu-Ser. Carp GRF is closely related structurally to peptides of the glucagon-secretin superfamily, and more particularly to mammalian vasoactive intestinal peptide (VIP) precursors and the N-terminal portion of mammalian GRFs. A synthetic replicate of this peptide is highly potent [50% effective dose (ED50) approximately 0.08 nM] in stimulating GH release from cultured goldfish pituitary glands and in elevating serum GH levels 30 min after injection (0.1 micrograms/g) in goldfish.
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PMID:Isolation and characterization of hypothalamic growth-hormone releasing factor from common carp, Cyprinus carpio. 147 12

Vasoactive intestinal polypeptide (VIP) is a neuropeptide, which also modulates some immune functions. Natural killer (NK) cell activity was already found to be diminished by VIP. In the present paper we report that VIP is able to decrease NK cell activity of human large granular lymphocytes (LGL), showing maximal inhibition at doses ranging from 10(-8) to 10(-6) M. Some neuropeptides, belonging to the VIP family (secretin, glucagon, peptide histidine isoleucine, PHI and human growth hormone releasing factor, GHRF), were also tested. Among these peptides, secretin and PHI were shown to be uneffective on NK cell activity whereas glucagon and GHRF were inhibitory. The D50 of GHRF was similar to that of VIP (10(-9) M), the D50 of glucagon was 10(-8) M. A recently synthesized VIP-antagonist (4Cl-D-Phe6-Leu17) was then used to assess its ability to reverse the VIP-mediated inhibition of NK activity. The antagonist was able to completely reverse the inhibitory effect of VIP on NK activity. The VIP-antagonist was also able to reverse the inhibitory effect of glucagon and GHRF, even though to a lesser extent than for VIP. Our data provide a new physiological observation regarding the functional activity of LGL, supporting the presence of a receptor for VIP on human LGL with NK activity.
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PMID:Modulation of human natural killer activity by vasoactive intestinal peptide (VIP) family. VIP, glucagon and GHRF specifically inhibit NK activity. 157 3


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