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 mechanisms underlying the renal hemodynamic responses (vasodilation and hyperfiltration) to an amino acid or protein load are currently unknown and are relevant to understanding the effect of dietary protein on the progression of chronic renal failure. Glucagon (GLC) has been suggested to be important in these renal hemodynamic responses, although the mechanism is again unclear. Thus we investigated potential mediators of the renal hemodynamic response to GLC in the anesthetized rat, including prostanoids and endothelium-derived relaxing factor (EDRF). The effects of glucagon alone and after pretreatment were tested as follows: (1) after baseline renal hemodynamic measurements done with clearance techniques, rats were given GLC alone (n = 5; 200 ng/min IV continuous infusion); (2) glucagon was given after pretreatment with the EDRF synthesis inhibitor nitro-arginine-methyl-ester (NAME; n = 6; 125 micrograms/kg/min intrarenal artery by continuous infusion); (3) glucagon was given after pretreatment with indomethacin (INDO; n = 6; 5 mg/kg IV bolus). Repeat clearances demonstrated that GLC infusion increased glomerular filtration rate (GFR; basal vs GLC, 0.87 +/- 0.04 ml/min vs 1.14 +/- 0.09 ml/min, p < 0.05); renal plasma flow (RPF; 4.10 +/- 0.18 ml/min vs 5.56 +/- 0.32 ml/min, p < 0.05) and decreased renal vascular resistance (RVR; 15.82 +/- 1.17 mm Hg/[ml/min] vs 10.72 +/- 0.65 mm Hg/[ml/min], p < 0.05). Intrarenal N-nitro-L-arginine-methyl-ester (NAME) infusion significantly reduced basal GFR (-20% +/- 8%, p < 0.05) and RPF (-43% +/- 2%, p < 0.05), while increasing RVR (+108% +/- 9%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of glucagon-induced renal vasodilation: role of prostaglandins and endothelium-derived relaxing factor. 145 14

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

Accumulating evidence from clinical and experimental studies indicates that the incretin glucagon-like peptide-1 (GLP-1) elicits blood-pressure lowering effects via its diuretic, natriuretic and vasodilatory properties. The present study investigated whether acute infusion of GLP-1 induces diuresis and natriuresis in spontaneously hypertensive rats (SHRs). Additionally, we examined whether GLP-1 influences the vascular reactivity of the renal arteries of normotensive and hypertensive rats and elucidated the underlying mechanisms. We found that the increase in urinary output and urinary sodium excretion in response to systemic infusion of GLP-1 for 30min in SHRs was much less pronounced than in normotensive rats. The diuretic and natriuretic actions of GLP-1 in normotensive rats were accompanied by increases in GFR and RBF and a reduction in RVR through activation of the cAMP signaling pathway. However, no changes in renal hemodynamics were observed in SHRs. Similarly, GLP-1 induced an endothelium-independent relaxation effect in the renal arteries of normotensive rats, whereas the renal vasculature of SHRs was unresponsive to this vasodilator. The absence of a GLP-1-induced renal artery vasodilator effect in SHRs was associated with lower expression of the GLP-1 receptor, blunted GLP-1-induced increases in cAMP production and higher activity and expression of the GLP-1 inactivating enzyme dipeptidyl peptidase IV relative to the renal arteries of normotensive rats. Collectively, these results demonstrate that the renal acute responses to GLP-1 are attenuated in SHRs. Thus, chronic treatment with incretin-based agents may rely upon the upregulation of GLP-1/GLP-1 receptor signaling in the kidneys of hypertensive patients and experimental models.
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PMID:Attenuated diuresis and natriuresis in response to glucagon-like peptide-1 in hypertensive rats are associated with lower expression of the glucagon-like peptide-1 receptor in the renal vasculature. 2857 4