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)

Growth and lactation are complex processes controlled by several metabolic hormones such as insulin, glucagon, and thyroid hormones but most notably growth hormone. Growth hormone secretion is regulated by two hypothalamic hormones, somatostatin, an inhibitory regulatory factor, and growth hormone-releasing factor. The quantity and pattern of growth hormone secretion is ultimately regulated in concert by the secretion of both regulatory factors from the hypothalamus through the hypothalamo-hypophyseal portal system, where they exert their actions at unique pituitary receptors. Because the potential use of exogenous growth hormone administration for the stimulation of growth efficiency and lactation has been demonstrated, recent efforts have been directed toward the enhancement of production through manipulation of endogenous growth hormone secretion via its releasing factor. Thus far, releasing factor-stimulated growth and lactation has not been achieved to the same extent as that of exogenous growth hormone. Growth hormone-releasing factor has stimulated growth in two growth hormone-deficient children, as well as female, but not male, rats. Although all food-producing species tested to date respond to growth hormone-releasing factor with the appropriate growth hormone response, continuous or pulsatile administration of releasing factor has not resulted in increased growth rate in sheep, chicks, or hogs. Despite levels of circulating growth hormone that would be expected to produce a 30% increase in milk production if given exogenously to dairy cows, releasing factor-stimulated growth hormone secretion has resulted in only a 3 to 9% increase. It is clear from these studies that further developments are necessary to demonstrate the practical application of growth hormone-releasing factor.
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PMID:Growth hormone-releasing factor effects on pituitary function, growth, and lactation. 310 44

The growth hormone (GH) responses to (A) GRF 1-44, 1 microgram/kg i.v., (B) L-dopa and either arginine, insulin, or glucagon, and (C) exercise were evaluated in 10 children (3 girls, 7 boys; ages 10 years to 15 years, 8 months), 2-10.75 years following cranial irradiation for medulloblastoma (8 patients), pineoblastoma (1 patient), and a fourth ventricular ependymoma (1 patient). Nine of the 10 children had abnormal growth rates. All children were euthyroid at the time of the study. The mean 0-60-min peak GH response to GRF (10.06 +/- 2.6 ng/ml) in the patients was less than the mean peak GH response (29 +/- 2.3 ng/ml) in the control children (n = 7). In 6 patients (5 with poor growth rates), a decreased GH response was noted to GRF and all other tests. Of the remaining patients, all with poor growth rates, two patients demonstrated an adequate response to GRF and pharmacologic testing; one patient had a normal GH response to GRF with a low GH response to pharmacologic testing; and one patient had a low response to GRF, despite a normal response to both exercise and pharmacologic testing. The decrease in mean peak GH response to GRF in the patient population confirms that radiation to the hypothalamic-pituitary region produces abnormalities in growth hormone release. Furthermore, in these patients, discordant GH responses to GRF and pharmacologic or physiologic tests can be observed. The abnormality in growth hormone release may result from a hypothalamic dysfunction in GRF release and/or damage to GH secretory pituicytes.
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PMID:Growth hormone response to GRF 1-44 in children following cranial irradiation for central nervous system tumors. 311 29

The results of testing growth hormone (GH) reserve using human pancreatic growth hormone-releasing factor 1-44 amide (hp GRF 1-44 amide) have been compared with the GH responses in a variety of other dynamic tests in seven acromegalic patients. The GH release following hp GRF 1-44 amide correlated with the GH suppression following bromocriptine, but showed an inverse correlation with the GH release following stress tests (insulin-induced hypoglycaemia/glucagon). There was no correlation between the GH responses in these three tests and any of the other tests: TRH, GnRH and glucose. A hypothesis is proposed to explain these findings on the basis of varying degrees of GH secretion from adenomatous and normal pituitary somatotrophs in acromegaly.
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PMID:Growth hormone responses to hp GRF 1-44 amide, bromocriptine and stress in acromegaly are correlated. 312 Jan 67

Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.
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PMID:Endocrine cells producing regulatory peptides. 329 70

Vasoactive intestinal peptide (VIP)-immunoreactive nerve fibers have been demonstrated in the rat adrenal cortex in close association with zona glomerulosa cells, suggesting neural regulation of adrenocortical cell function (5). The present studies were undertaken to study the possible role of VIP in the regulation of steroid hormone secretion from the outer zones of the normal rat adrenal cortex. Capsule-glomerulosa preparations, consisting of the capsule, zona glomerulosa, and a small but variable portion of the zona fasciculata, were perifused in vitro. To assess the secretory responsiveness of the capsule-glomerulosa preparation, aldosterone and corticosterone release were measured after stimulation with ACTH and angiotensin II. ACTH (10(-12)-10(-8) M) stimulated dose-dependent increases in aldosterone secretion (1.9- to 36.9-fold increases over basal values) and corticosterone secretion (1.4- to 14.0-fold increases over basal values). Angiotensin II (10(-8)-10(-5) M) stimulated dose-dependent increases in aldosterone secretion (1.6- to 8.8-fold increases over basal values). VIP (10(-6)-10(-4) M) stimulated dose-dependent increases in both aldosterone (1.7- to 41.0-fold) and corticosterone secretion (1.8- to 5.3-fold). However, glucagon and (N-Ac-Tyr1-D-Phe2)GRF-(1-29)NH2, peptides structurally related to VIP, stimulated neither aldosterone nor corticosterone secretion, indicating that VIP effects are likely to be specific for this peptide. It is noteworthy that in this preparation, the stimulation of corticosteroid secretion by VIP at 10(-5) and 10(-4) M was comparable to those by 10(-6) M angiotensin II and 10(-9) M ACTH, respectively. These results support the hypothesis that the VIP innervation of the adrenal cortex may contribute directly to the regulation of adrenal steroidogenesis.
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PMID:Vasoactive intestinal peptide stimulates adrenal aldosterone and corticosterone secretion. 335 77

An oral protein load or infusion of amino acids induces a rise in renal hemodynamics in normal subjects, but the mechanisms mediating this phenomenon are unknown. We investigated whether glucagon may mediate the increase in RPF and GFR induced by an arginine infusion and whether prostaglandins are required for this effect. In four different studies, normal subjects underwent 13 inulin and PAH clearances of 30 minutes each. During the fourth and tenth clearance periods arginine HCl, 250 mg/kg, was infused over 30 minutes. At the beginning of the fifth clearance period several subjects ingested indomethacin, 150 mg, (N = 8) or ibuprofen, 800 mg (N = 6). Control subjects (N = 4) did not receive cyclooxygenase inhibitors. Six subjects underwent a similar protocol except that they were infused with glucagon, 6 ng/kg/min, instead of arginine, for 30 minutes during the fourth and tenth periods. They also ingested indomethacin, 150 mg, in the fifth period. In all four studies, a transient and significant rise in RPF and GRF and fall in RVR occurred during the first arginine or glucagon infusion. These changes in renal hemodynamics were blocked when the arginine or glucagon infusion was repeated after administration of indomethacin or ibuprofen. Urinary excretion of 6-keto-PGF1 alpha did not rise with either arginine infusion in the control subjects or in the individuals who received indomethacin. As predicted, urinary 6-keto-PGF1 alpha fell significantly after ingestion of indomethacin before the second infusion of arginine. Plasma norepinephrine and epinephrine concentrations were unaffected by the arginine infusions or by indomethacin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucagon and prostaglandins are mediators of amino acid-induced rise in renal hemodynamics. 340 14

Bombesin-like immunoreactivity (BLI), a putative peptidergic neurotransmitter of the gastrointestinal intrinsic nervous system is released from the isolated perfused rat stomach in response to the classical neurotransmitter acetylcholine and in response to other putative peptidergic neurotransmitters such as vasoactive intestinal peptide (VIP), peptide histidine isoleucine (PHI) or growth hormone releasing factor (GRF). The secretion of BLI is modulated not only by gastric factors such as the intragastric pH but also by changes of perfusate glucose concentrations indicating that alterations of carbohydrate metabolism might have an effect on gastric neuroendocrine regulation. Since previous studies have shown that insulin, the major regulatory hormone of glucose metabolism, reduces gastric somatostatin and glucagon secretion it was of interest to determine the effect of insulin on gastric BLI and gastrin secretion. The experiments were performed in the isolated perfused rat stomach model. The addition of porcine insulin to the perfusate at concentrations of 50 and 100 microU/ml had no effect on basal BLI and gastrin secretion. The infusion of acetylcholine (2 X 10(-6)M and 4 X 10(-6)M) elicited a stimulation of BLI and gastrin secretion which was not altered by the addition of insulin (100 microU/ml). On the other hand, significant effects of insulin were observed during administration of the two putative peptidergic neurotransmitters VIP and leu-enkephalin. The infusion of VIP at 10(-11)M and 10(-8)M had no effect on BLI and gastrin secretion in the absence of insulin, however, with the addition of insulin (100 microU/ml) the higher dose of VIP (10(-8)M) elicited a significant stimulation of BLI secretion while both doses of VIP (10(-11)M and 10(-8)M) significantly increased gastrin release. Similar to VIP the infusion of leu-enkephalin at doses of 10(-9)M and 10(-6)M had no effect on BLI and gastrin secretion in the absence of insulin. When insulin was added to the perfusate both doses of leu-enkephalin elicited a significant stimulation of BLI secretion while gastrin remained unchanged. The addition of the specific opiate receptor antagonist naloxone (10(-5)M) did not block the effect of leu-enkephalin in the presence of insulin. In addition the effect of naloxone was also examined during cholinergic stimulation. The addition of naloxone (10(-5)M) during the infusion of acetylcholine abolished the stimulatory effect on BLI secretion in the absence of insulin, whereas in the presence of insulin naloxone did not alter cholinergically-induced BLI secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of insulin on secretion of bombesin-like immunoreactivity and gastrin from the isolated rat stomach in response to acetylcholine, VIP and leucine-enkephalin. 351 44

1. The effect of vasoactive intestinal polypeptide (VIP) upon adenylate cyclase activity was determined in purified cortical basolateral membranes and in glomeruli and tubular elements obtained from rabbit kidney. 2. In purified basolateral membranes prepared from cortex, 1 microM-VIP consistently stimulated adenylate cyclase activity above basal levels (1.55 +/- 0.09-fold (mean +/- S.E. of mean), n = 10 animals). Half-maximal stimulation was observed at 17 +/- 11 nM-VIP (S.D., n = 9). 3. Related peptides, e.g. secretin, glucagon, gastric inhibitory peptide, human pancreatic growth hormone releasing factor, and peptide having N-terminal histidine and C-terminal isoleucine amide (PHI), were without effect or gave lower stimulations of adenylate cyclase activity when tested at 1 microM. 4. Significant VIP degradation was observed under the assay conditions used but this did not substantially alter the response or selectivity to VIP. 5. In separate preparations of isolated glomeruli and proximal tubules addition of 1 microM-VIP resulted in a 3.3 +/- 1.1-fold (S.D., n = 3) and 2.2 +/- 1.0-fold (S.D., n = 3) stimulation (respectively) of adenylate cyclase activity. 6. In isolated medullary tubule suspensions, isolated by collagenase-hyaluronidase digestion of outer (red) medulla, and in thick ascending-limb-enriched preparations prepared by Percoll density gradient fractionation, 1 microM-VIP significantly increased adenylate cyclase activity by 2.4 +/- 0.6-fold (S.D., n = 3) and 2.1 +/- 0.7-fold (S.D., n = 3) respectively. 7. A possible role for VIP in the regulation of renal function in the rabbit is discussed in relation to the occurrence of VIP stimulation of adenylate cyclase activity in several renal cellular elements.
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PMID:Vasoactive intestinal polypeptide regulation of rabbit renal adenylate cyclase activity in vitro. 365 72

The functions of the Trp-25 and Met-27 residues and the free carboxy terminus of glucagon have been debated for many years. Despite some semi-synthetic data to the contrary, comparison of the glucagon sequence with the other 5 members of this family of peptides, all of them amides and particularly growth hormone-releasing factor(1-29) amide and its recently described analogues, suggests that alterations to these positions should be quite well tolerated in terms of biological activity. To test this prediction, [Phe-25,Leu-27]-glucagon amide was synthesized in high yield and was found to actually have superior glycogenolytic activity (196%) to glucagon in the rat. Replacement of Gly-4 by D-Phe, which has been shown to give much enhanced glycogenolytic activity than glucagon itself, also increased the activity of [D-Phe-4,Phe-25,Leu-27]-glucagon amide (518%). The L-Phe-4-analogue, [Phe-4,25,Leu-27]-glucagon amide, in contrast, was 20 times less active (30%), strongly suggesting the presence of a beta-bend in this N-terminal region of glucagon. This was supported by Chou-Fasman structural predictions which indicate extensive folding in the 1-15 region. Indeed, additional conformational restriction by substitution of D-Ser in position 2 of glucagon also increased activity to 226%. [D-Gln-3]-glucagon was slightly less active (74%) than glucagon. Chou-Fasman calculations on glucagon were compared to similar treatments of the VIP, secretin, PHI, and GRF(1-29) sequences.
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PMID:Superactive amidated COOH-terminal glucagon analogues with no methionine or tryptophan. 374 51

Two adult patients with unilateral hypoplastic optic nerves, absent septa pellucida and hypopituitarism are described. Patient 1, aged 20, presented with diabetes insipidus due to partial vasopressin deficiency. Patients 2, aged 29, presented with focal epilepsy. Both had short stature. They showed absent growth hormone (GH) response to insulin-hypoglycaemia or glucagon, but responded to 100 micrograms growth hormone releasing factor (GRF-44) with a rise in circulating GH, suggesting a hypothalamic defect in GH release though a co-existing pituitary defect cannot be excluded. Other hypothalamic-pituitary functions were normal. These two patients probably represent the milder form of the clinical spectrum of septo-optic dysplasia which, with the extensive use of CT brain scans, will be increasingly encountered by physicians attending adult patients.
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PMID:Hypothalamic defects in two adult patients with septo-optic dysplasia. 375 51


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