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)

Heparin was found to be the most potent inhibitor of rat ovarian luteinizing hormone-sensitive adenylate cyclase (I50 = 2 microgram/ml) when compared to other naturally occurring glycosamin oglycans. This inhibition was also apparent when this enzyme was stimulated by follicle-stimulating hormone or prostaglandin E2. Heparin was also found to inhibit glucagon-sensitive rat hepatic adenylate cyclase, and the prostaglandin E1-sensitive enzyme from rat ileum and human platelets. In contrast, heparin stimulated the dopamine sensitive adenylate cyclase from rat caudate nucleus. The sulfated polysugar dextran sulfate exerts similar effects on adenylate cyclase activity of the rat ovary and was shown to inhibit hormone binding to rat ovarian plasma membrane in a manner similar to that exerted by heparin. In contrast to heparin, dextran sulfate inhibited dopamine-sensitive adenylate cyclase from rat caudate nucleus.
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PMID:Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. II. Effects of mucopolysaccharides and dextran sulfate on the activity of adenylate cyclase derived from various tissues. 15 57

Basic studies on the secretion of glucagon and insulin by the ovine pancreatic autotransplant in the neck are described. Of the 17 transplants in the series none failed to secrete glucagon and only three failed to secrete insulin in detectable amounts. The longest surviving transplant actively secreted both hormones 3 years after transplantation and five other transplants were functional and the animals healthy after 16 months. Exocrine secretion disappears shortly after transplantation. Sodium butyrate and alanine each promoted the secretion of both hormones by the transplant. Glucagon failed to promote insulin secretion by the transplant, although it apparently stimulated the ovine in situ pancreas. The immediate (presumably direct) effect of insulin was to inhibit transplant glucagon secretion. Hypoglycaemia induced by peripheral insulin administration failed to stimulate glucagon secretion by the transplant, although it did promote glucagon secretion by the ovine in situ pancreas. Heparin did not markedly suppress basal transplant secretion of either glucagon or insulin. Phasic response patterns occurred with both hormones during long butyrate perfusions, although first-phase responsiveness was not a constant feature. In one trial, first-phase responses fell off with repeated short butyrate infusions. Glucagon and insulin secretory patterns in response to butyrate were remarkably alike, suggesting a common mechanism. Loss of specific functions by the ovine pancreas after transplantation is discussed.
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PMID:Studies with the autotransplanted ovine pancreas: glucagon and insulin secretion. 79 Dec 27

Highly sulfated, heparinlike species of heparan sulfate proteoglycans, with heparinlike glycosaminoglycan chains, are extracellular matrix components that are plasma membrane bound in growth-arrested liver cells. Heparins were found to inhibit the growth and lower the clonal growth efficiency of HepG2, a minimally deviant, human hepatoma cell line. Heparan sulfates, closely related glycosaminoglycans present in the extracellular matrix around growing liver cells, had no effect on the growth rate or clonal growth efficiency of HepG2 cells. Neither heparins nor heparan sulfates had any effect on the growth rate or clonal growth efficiency of two poorly differentiated, highly metastatic hepatoma cell lines, SK-Hep-1 and PLC/PRF/5. Heparin's inhibition of growth of HepG2 cells correlated with changes in the mRNA synthesis and abundance of insulinlike growth factor II (IGF II) and transforming growth factor beta (TGF beta). HepG2 cells expressed high basal levels of mRNAs encoding IGF II and TGF beta that were inducible, through transcriptional and posttranscriptional mechanisms, to higher levels by specific heparin-hormone combinations. For both IGF II and TGF beta, the regulation was multifactorial. Transcriptionally, IGF II was regulated by the additive effects of insulin, glucagon, and growth hormone in combination with heparin; TGF beta was regulated primarily by the synergistic effects of insulin and growth hormone in combination with heparin. Posttranscriptionally, the mRNA abundance of the IGF II 4.5- and 3.7-kb transcripts was affected by insulin. Heparin induction of all IGF II transcripts was also dependent on triiodotyronine and prolactin, but it is unknown whether their induction by heparin was via transcriptional or posttranscriptional mechanisms. Heparin-insulin combinations regulated TGF beta posttranscriptionally. The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGF beta, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination. We discuss the data as evidence that matrix chemistry is a variable determining the expression of autocrine growth factor genes and the biological responses to them.
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PMID:Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors. 184 19

The effects of hyperglycemia on plasma fibrinopeptide A (FPA) levels in normal subjects are reported. An increase of FPA concentration parallel to sustained hyperglycemia was observed; when the glycemia returned to basal values, FPA showed values in normal range. Heparin infusion was able to significantly decrease the hyperglycemia-induced augment of FPA levels. Isovolumic-isotonic NaCl solution infusion produced a slight (NS) increase in FPA levels; however, mild hyperglycemia, achieved by glucagon, was also able to produce a significant increase in FPA concentration. These data demonstrate the direct role of hyperglycemia in conditioning FPA level, and suggest that hyperglycemia, by itself, is a sufficient stimulus to produce thrombin activation in humans.
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PMID:Hyperglycemia may determine fibrinopeptide A plasma level increase in humans. 259 29

We have investigated in normal subjects the possible role of plasma free fatty acids (FFA) and blood ketone bodies (KB) in the regulation of human somatostatin secretion. Heparin injected during the intravenous infusion of a fat emulsion raised FFA levels acutely from 0.4 +/- 0.1 to near 3 mmol/L. Plasma somatostatin-like immunoreactivity (SLI) rose from a mean (+/- SEM) basal value of 9.2 +/- 1.0 ng Eq S14/L to 20.0 +/- 6.0 ng Eq S14/L (P less than 0.05). Plasma immunoreactive insulin (IRI) level was unchanged and glucagon (IRG) concentration decreased from 156 +/- 20 to 107 +/- 2 ng/L (P less than 0.05). During this test, there was a rise not only in FFA but also in plasma triglycerides (TG) and in blood glycerol and KB levels. The infusion of a fat emulsion alone increased triglyceride and glycerol levels to a similar extent but induced also a mild rise of FFA (0.37 +/- 0.05 to 1.13 +/- 0.5 mmol/L, P less than 0.01), KB (78 +/- 12 to 360 +/- 45 mumol/L, P less than 0.01), and SLI (14.8 +/- 4.6 to 23.8 +/- 7.1 ng Eq S14/L, P less than 0.05). The induction by DL-Na-3-hydroxybutyrate infusion of a rise of KB was associated with a decrease of FFA (P less than 0.05) and SLI (P less than 0.05) without modification of IRI or IRG levels. Phentolamine infusion did not modify the SLI or glucagon response to acute elevations of FFA, whereas propranolol suppressed the increase of SLI without preventing the concomitant decrease of IRG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of somatostatin secretion in man: study of the role of free fatty acids and ketone bodies. 614 47

We aimed to investigate the role of phosphatidylinositol 3 (PI3)-kinase/Akt pathway on ischemic injury. Rat liver grafts were preserved in UW solution with different treatments and were compared by 1-week survival rates and morphological changes with those of the control group. PI3-kinase/Akt was significantly activated at the sites of Thr 308 and Ser 473 in the preserved grafts. Downstream target proteins, glycogen synthase kinase-3beta (GSK-3beta) and caspase-9, were inactivated. However, survival signal transduction from Akt to Bad was blocked by calcium release after activation of PI3-kinase/Akt. Significant activation of caspase-12, -3 and -7 contributed to cell apoptosis and severe ischemic injury was shown after 7 h of preservation by UW solution with insulin. Downregulation of phospho-Akt at Thr 308 and Ser 473 was due to partial inhibition of PI3-kinase/Akt pathway by LY294002. Activation of GSK-3beta and inactivation of caspase-12 and Bad could be found in the LY294002 groups in which the liver grafts showed less ischemic injury. Higher 1-week survival rates in the heparin, LY294002, and glucagon groups confirmed the dysregulation of the pathway. In conclusion, PI3-kinase/Akt pathway was dysregulated and contributed to ischemic injury during preservation. Heparin and LY294002 could improve graft viability by maintaining calcium homeostasis during preservation.
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PMID:The influence of phosphatidylinositol 3-kinase/Akt pathway on the ischemic injury during rat liver graft preservation. 1588 30

BETA2/NeuroD protein is important for regulating insulin gene transcription and for the terminal differentiation of islet cells, including insulin- and glucagon-producing cells. We reported that BETA2/NeuroD protein can permeate several cell types, including pancreatic islets, because of an arginine- and lysine-rich protein transduction domain (PTD) sequence in its structure. Here we provide genetic and biochemical evidence that cell membrane heparan sulfate proteoglycans are involved in extracellular BETA2/NeuroD internalization. We tested whether soluble glycosaminoglycans (GAGs) could inhibit BETA2/NeuroD internalization. Heparin almost completely prevented BETA2/NeuroD entry, whereas chondroitin sulfate A, B, and C caused only limited inhibition. Moreover, treatment with heparinase III impaired BETA2/NeuroD internalization, whereas treatment with chondroitinase ABC, or with chondroitinase AC, was completely ineffective in inhibiting BETA2/NeuroD internalization. We also examined various mutant cell lines originating from CHOK1 cells and defective in GAG biosynthesis. The observation using mutant cell lines supports the notion that the selective sulfation of heparan sulfate is an important determinant for NeuroD/heparan sulfate recognition. These data indicate that cell surface heparan sulfate proteoglycans are required for BETA2/NeuroD internalization and that BETA2/NeuroD protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology.
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PMID:BETA2/NeuroD protein transduction requires cell surface heparan sulfate proteoglycans. 1714 99