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)

The ability of synthetic corticotropin-releasing factor (CRF) (rat) to influence hormone release from the endocrine pancreas of rats has been evaluated by means of perfusion in situ. Release of insulin and glucagon into the perfusate was measured in the presence and absence of CRF (0.1, 1, and 10 ng/ml) under conditions of normal and high glucose concentration (5.5 and 11 mM). Under both conditions, CRF (0.1, 1, and 10 ng/ml) induced a rapid, dose-dependent inhibition of insulin release followed by a remarkable postinhibitory rebound when exposure to CRF was discontinued. CRF had no significant effect on glucagon release when tested under these conditions. These results are reminiscent of noradrenergic inhibition of insulin release and together with evidence for the presence of CRF in the pancreas suggest that this peptide could function as a neuromodulatory transducer in addition to its role as a hypophysiotropic hormone perhaps contributing to the coordination of the overall endocrine response to stress.
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PMID:Corticotropin-releasing factor inhibits insulin release from perfused rat pancreas. 389 May 60

Bombesin was injected into the cerebral ventricle of male rats anesthetized with urethane to study its effect on plasma levels of immunoreactive somatostatin (IRS) in hypophysial portal and jugular blood. An intraventricular injection of bombesin (0.2 and 2 micrograms/rat) caused a significant and dose-related increase in plasma IRS in hypophysial portal blood but not in jugular blood. Although bombesin placed into the cerebral ventricle is known to stimulate glucagon and epinephrine release, an iv injection of glucagon (100 micrograms/100 g BW) or epinephrine (2.5 micrograms/100 g BW) did not cause any significant changes in plasma IRS levels in hypophysial portal and jugular blood, suggesting that these substances do not mediate bombesin stimulation of portal IRS release. Pretreatment with naloxone (75 micrograms/100 g BW, iv) failed to affect the portal IRS release induced by bombesin (2 micrograms/rat), indicating that the opiate receptor is not likely to be involved in this reaction. To ascertain whether IRS released by bombesin into hypophysial portal blood is biologically active, the effect of bombesin on the plasma GH level was then examined. Bombesin (2 micrograms/rat) injected intraventricularly completely suppressed the rise of plasma GH after the intraventricular injection of beta-endorphin (1 microgram/rat) or the iv injection of prostaglandin E1 (5 micrograms/100 g BW). Bombesin thus appears to stimulate the secretion of IRS, and probably biologically active somatostatin as well, from the hypothalamus into hypophysial portal blood, thereby inhibiting GH release from the anterior pituitary.
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PMID:Stimulation by bombesin of immunoreactive somatostatin release into rat hypophysial portal blood. 611 30

Specific SRIF(1-14) fragments were synthetized on resin using conventional procedures. Rabbits received subcutaneously peptidyl resins in complete Freund adjuvant emulsion. The presence of antibodies was assessed by immunocytochemical and radioimmunological assays. 1. Peptidyl resins lead to antibodies production; their specificity depends on sequence and molecular configuration of the peptide on the resin. Anti-resin antibodies were not detected. 2. In the brain, SRIF(1-4) (in rat) and SRIF(10-13) (in garden-dormouse) can be demonstrated in neurophysins--positive cells of both paraventricular and supraoptic nucleus, but never in hypothalamic or extrahypothalamic SRIF(1-14)--positive neurophysin negative cells. 3. Endocrine cells of pancreatic islets contain SRIF(6-9) (in man) or SRIF(10-13) (in rat, mouse, garden-dormouse); generally, these cells are not detected by SRIF(1-14) anti-serum. Moreover, SRIF(10-13) positive cells are also detected by specific glucagon antibodies. However, it cannot be concluded that SRIF(10-13) antibodies reveal the common Thr-Phe-Thr-Ser fragment in the entire glucagon molecule. It is postulated that antibodies to several SRIF tetrapeptides reveal molecular fragments provided by the functional cleavage of an hypothetical prohormone or by the inactivation of SRIF(1-14) molecule in target cells.
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PMID:[Preparation of antisera against some sequences of somatostatin synthetized on resin. Application to the immunological detection of somatostatin systems: preliminary results (author's transl)]. 612 35

The role of central glucagon in regulating GH secretion was studied in conscious male rats with chronic indwelling intra-atrial and intracerebro-ventricular (ICV) cannulae. Repeated blood sampling every 20 min from 1000 hr to 1700 hr showed two major GH bursts occurring at regular intervals (3.6 +/- 0.1 hr) around 1200 hr and 1540 hr. The ICV (lateral ventricle) injection of glucagon (10 micrograms/rat) at 1100 hr inhibited spontaneous GH secretion, and the mean (+/- SE) plasma GH levels from 1120 hr to 1700 hr were lower than those in controls injected ICV with the vehicle solution only (31.9 +/- 7.8 ng/ml vs. 157.1 +/- 13.4 ng/ml, p less than 0.01). The GH bursts did not appear until 5 hr after the injection. The intravenous (IV) injection of glucagon (10 micrograms/rat) did not change plasma GH levels or the occurrence of spontaneous GH bursts. The glucagon-induced suppression of GH release was attenuated when anti-somatostatin serum (ASS), but not normal rabbit serum (NRS), was given IV in a volume of 0.25 ml immediately before the ICV injection of glucagon (10 micrograms/rat) (mean GH levels at 1120-1700 hr: ASS + glucagon, 133.6 +/- 26.7 ng/ml vs. NRS + glucagon, 30.5 +/- 7.4 ng/ml, p less than 0.01). These findings suggest that central glucagon may play an inhibitory role in regulating GH secretion by stimulating SRIF release from the hypothalamus in the rat.
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PMID:Involvement of hypothalamic somatostatin in glucagon-induced suppression of growth hormone secretion in conscious rats. 614 99

The interrelationship between SRIF output from the mediobasal hypothalamus and plasma GH levels was studied in conscious male rats using the push-pull perfusion technique in combination with repeated blood samplings. The MBH was perfused with artificial cerebrospinal fluid at the rate of 30 microliter/min, and blood samples were collected every 20 min from 1000-1700 h. In control animals, which received injection of acidified saline at 1100 h into the lateral ventricle, two large episodes of spontaneous GH secretion occurred regularly at around 1200 and 1540 h, and troughs occurred around 1400 h. In contrast, SRIF levels from mediobasal hypothalamus perfusate fluctuated at random, ranging from 10-116 pg/ml, with a mean value of 39.2 pg/ml. Mean SRIF levels at 1200 and 1540 h (43.4 +/- 9.0 and 24.4 +/- 4.2 pg/ml, respectively; n = 8) were not different from those at 1400 h (39.9 +/- 12.2 pg/ml). When glucagon (10 micrograms/rat) was injected at 1100 h, plasma GH levels decreased and remained low until 1600 h, whereas perfusate SRIF levels were elevated and remained high for the period. In these animals, the mean plasma GH levels during 1120-1540 h were lower than those in control rats [17.2 +/- 2.4 ng/ml (n = 9) vs. 143.4 +/- 17.5 ng/ml (n = 8); P less than 0.01]. In contrast, the mean SRIF levels in glucagon-treated rats were higher than those in controls [112.5 +/- 15.9 pg/ml (n = 9) vs. control 40.1 +/- 4.3 pg/ml (n = 8); P less than 0.01]. These results suggest that SRIF plays a role in tonic inhibition of GH release in response to the intracerebroventricular injection of glucagon in conscious rats, although SRIF plays, if any, a minor role in regulating episodic GH secretion.
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PMID:Interrelation between somatostatin output from the mediobasal hypothalamus and plasma growth hormone levels in conscious rats: effects of glucagon administration. 614 35

By immunofluorescence and double labelled anti sera L and M pyruvate kinase, there is a double localization of isozymes. It is detected in basal state, in vitro, in isolated hepatocyte, in vivo in experimental or genetic (Zucker rat) hyperinsulinemia or in regenerating liver following partial hepatectomy. It is found in hepatology, in regenerative nodule of cirrhosis and in cancerous cells of liver. This double presence of L and MPK tallies with a specific double hormonodependence: induction of MPK by insulin, and inhibition of LPK by glucagon.
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PMID:[L and M isoenzymes of hepatic pyruvate kinase and their hormone dependence]. 622 Jul 89

Using immunofluorescence and double-labelled antisera L and M pyruvate kinase (PK), we show that PK is localized in hepatocyte cytoplasm. The response is modulated by different dietary and hormonal conditions. In physiological conditions, only L PK is noted: slight with normal diet (or 35 micrograms of glucagon) and non-existent with starvation (or 350 micrograms of glucagon). L PK fluorescence is maximal after a carbohydrate-rich diet. In experimental or genetic (Zucker rat) hyperinsulinemia, hepatocytes are both L PK and M PK positive. After partial hepatectomy, this double specificity is found between 48 h and the 7th day. The decrease of PK fluorescence after starvation or glucagon concerns the L PK form of the enzyme. With exo- or endogenous insulin, the increase of PK (as insulinemia assays from Zucker rats or after partial hepatectomy confirm) is essentially due to the presence of M PK in hepatocytes.
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PMID:Cytoimmunochemical study of pyruvate kinase isoenzymes in rat liver. 676 79

Substantial in vitro evidence suggests that nitric oxide may be a major mediator of interleukin 1 (IL-1) induced pancreatic beta-cell inhibition and destruction in the initial events leading to insulin-dependent diabetes mellitus. Using NG-nitro-L-arginine methyl ester, an inhibitor of both the constitutive and the cytokine inducible forms of nitric oxide synthase, and aminoguanidine, a preferential inhibitor of the inducible form of nitric oxide synthase, we investigated the impact of inhibiting nitric oxide production on food-intake, body weight and temperature, blood glucose, plasma insulin, glucagon, corticosterone and leukocyte- and differential-counts in normal rats injected once daily for 5 days with interleukin 1 beta (IL-1 beta) (0.8 microgram/rat = 4.0 micrograms/kg). Inhibition of both the constitutive and the inducible forms of nitric oxide synthase prevented IL-1 beta-induced fever, hyperglycaemia, hypoinsulinemia, and hyperglucagonemia, and partially prevented lymphopenia and neutrophilia, but had no effect on IL-1 beta-induced anorexia and changes in plasma corticosterone. Preferential inhibition of the inducible form of nitric oxide synthase using two daily injections of 5 mg/rat of aminoguanidine prevented IL-1 beta-induced hyperglycaemia and hypoinsulinaemia, and slightly reduced the pyrogenicity of IL-1 on 3 out of 5 days. Higher doses of aminoguanidine (100 mg/rat) prevented lymphopenia and neutrophilia. We conclude that nitric oxide produced by the inducible form of nitric oxide synthase, mediates the IL-1 beta-induced inhibition of insulin release and that the effect of IL-1 beta on temperature, pancreatic alpha-cells, and leukocyte differential counts seems to be mediated by nitric oxide produced by the constitutive form of nitric oxide synthase.
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PMID:Interleukin 1 beta induces diabetes and fever in normal rats by nitric oxide via induction of different nitric oxide synthases. 753 59

Pituitary adenylate cyclase activating polypeptide (PACAP) is a new member of the secretin-glucagon-vasoactive intestinal peptide (VIP) peptide family. PACAP is widely distributed not only in the mammalian brain but also in the gastrointestinal tract. Here, we investigated the effects of central and peripheral administrations of PACAP on gastric motility and gastric emptying in rats. We found that the intracerebroventricular or intracisternal injection of PACAP increased gastric motility in a dose-dependent manner. The intracisternal injection of PACAP delayed gastric emptying. These central effects of PACAP on gastric motility and emptying were blocked by bilateral vagotomy. In contrast, intravenous administration of PACAP decreased gastric motility and delayed gastric emptying. The peripheral inhibitory effect was unaffected by bilateral vagotomy, adrenalectomy, phentolamine, and propranolol. We investigated the effect of PACAP38 on blood glucose levels (BGL) at the same doses as those used in the gastric motility and emptying studies in urethane-anesthetized rats. The intravenous but not intracerebroventricular injection of PACAP38 (1-8 nmol/rat) produced a significant increase in the BGL. We conclude that PACAP has opposite central and peripheral effects on gastric motility, ie, central PACAP activates the vagal pathway in the central nervous system to increase gastric motility, whereas peripheral PACAP inhibits gastric motility via an unknown pathway. The delay in gastric emptying after the central administration of PACAP might be due to the lack of coordinated gastropyloroduodenal contraction, whereas that after the peripheral administration might be due to the inhibition of gastric contraction, and this effect may be related to the hyperglycemic action of PACAP.
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PMID:Central effects of pituitary adenylate cyclase activating polypeptide (PACAP) on gastric motility and emptying in rats. 1021 31

Gastric inhibitory polypeptide (GIP) is a 42-amino acid peptide, belonging to the VIP-secretin-glucagon superfamily, some members of this group are able to regulate adrenocortical function. GIP-receptor mRNA has been detected in the rat adrenal cortex, but investigations on the effect of GIP on steroid-hormone secretion in this species are lacking. Hence, we have investigated the distribution of GIP binding sites in the rat adrenal gland and the effect of their activation in vivo and in vitro. Autoradiography evidenced abundant [125I]GIP binding sites exclusively in the inner adrenocortical layers, and the computer-assisted densitometric analysis of autoradiograms demonstrated that binding was displaced by cold GIP, but not by either ACTH or the selective ACTH-receptor antagonist corticotropin-inhibiting peptide (CIP). The intraperitoneal (IP) injection of GIP dose-dependently raised corticosterone, but not aldosterone plasma concentration: the maximal effective dose (10 nmol/rat) elicited a twofold increase. GIP did not affect aldosterone and cyclic-AMP release by dispersed zona glomerulosa cells. In contrast, GIP enhanced basal corticosterone secretion and cyclic-AMP release by dispersed inner adrenocortical cells in a concentration-dependent manner, and the maximal effective concentration (10(-7) M) evoked 1.5- and 2.4-fold rises in corticosterone and cyclic-AMP production, respectively. GIP (10(-7) M) did not display any additive or potentiating effect on corticosterone and cyclic-AMP responses to submaximal or maximal effective concentrations of ACTH. The corticosterone secretagogue action of 10(-7) M GIP was abolished by the protein kinase A (PKA) inhibitor H-89 (10(-5)M), and unaffected by CIP (10(-6)M). Collectively, these findings indicate that GIP exerts a moderate but statistically significant stimulatory effect on basal glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase/PKA-dependent signaling pathway.
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PMID:Gastric inhibitory polypeptide stimulates glucocorticoid secretion in rats, acting through specific receptors coupled with the adenylate cyclase-dependent signaling pathway. 1046 10


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