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 in small intravenous (i.v.) doses markedly increases glomerular filtration rate (GFR) in normal anesthetized dogs. In this study, the effects of glucagon 5 mug/min (i.v.) on renal hemodynamics was tested in four canine models of acute pre-renal failure (hemorrhage, barbiturate overdose; renal arterial clamping and renal arterial infusions of noradrenaline) and in a model of unilateral acute tubular necrosis at 4 h and 6-7 days following completion of the ischemic insult. Following hemorrhage and barbiturate excess, with arterial blood pressure maintained at 65-70 mm Hg, whole-kidney GFR and clearance rate of p-aminohippurate decreased by 50-70%. During this reduction of perfusion pressure, the subsequent infusion of glucagon increased GFR by 90-130%. In models where arterial pressure was normal during the period of ischemia (clamping and noradrenaline infusion), not only did glucagon significantly increase renal perfusion, but the ischemic kidney proved to be far more sensitive to the hemodynamic effects of glucagon (delta GFR - 120-160%) than the contralateral control (deltaGFR = 30-40%). In three dogs completely anuric following renal arterial clamping, glucagon was able to improve blood flow and restart urine formation. Glucagon, but not dopamine, was able to simulate the beneficial effects of hypertonic mannitol on renal function in dogs with hemorrhagic hypotension. Glucagon was without effect in established acute tubular necrosis. This study, therefore, indicates that, during renal ischemia, glucagon may be quite effective in preserving urine output and perfusion of the kidneys.
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PMID:The effect of glucagon on glomerular filtration rate in dogs during reduction of renal blood flow. 117 90

Preformed arterial collaterals are critical to renal parenchymal survival after acute total renal artery occlusion. This study was designed to delineate and quantify preformed collaterals and assess their response to vasodilators. A Swan-Ganz catheter induced a sudden, total occlusion of a renal artery sufficient to reduce distal arterial pressure to near zero and prevent perfusion through the renal artery. Arteriography assessed the effectiveness of the occlusion and delineated the collateral arterial pathways. Strontium, cerium-, and chromium-labeled microspheres measured renal blood flow and cardiac output 1, 60, and 120 minutes after occlusion. In two additional series of experiments either contralateral nephrectomy was performed 5 to 8 days before the study, or dibenzylene, dopamine, or glucagon were administered in an attempt to increase blood flow through the collaterals. Collateral renal blood flow was demonstrated in all dogs. Mean blood flow to the occluded kidneys ranged from 0.13 +/- 0.05 cm3/minute/g to 0.22 +/- 0.08 cm3/minute/g, about 5% of control values. Neither prior contralateral nephrectomy nor vasodilator agents increased the flow to the obstructed kidneys. In the dogs with intact contralateral kidneys, however, there was a progressive decrease in cardiac output during the experiment, which was not found in uninephrectomized animals. We concluded that preformed arterial channels are available to maintain a small, but probably critical level of perfusion following sudden total occlusion of the renal artery. Neither hypertrophy due to prior contralateral nephrectomy nor active vasodilators modify flow through the preformed channels. It is likely that total renal ischemia provides a maximal stimulus for vasodilatation. The pattern of hind limb collaterals differed strikingly from those of the kidney, with maintenance of a greater portion of a normal flow and rapid increase in flow within 1 hour after femoral artery occlusion. Thus, data concerning collateral circulation cannot be generalized from one vascular bed to another even in the same species.
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PMID:Renal collateral blood supply after acute unilateral renal artery occlusion. 120 8

Incretin-based therapies, including glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, are potent glucose-lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology to GLP-1 (liraglutide and semaglutide) but neither exenatide-based GLP-1 receptor agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This different response might relate to GLP-1 receptor-independent actions of GLP-1 caused by cleavage products only liberated by GLP-1 receptor agonists with close peptide structure to GLP-1. To test this hypothesis, we directly compared metabolic, renal, and cardiac effects of GLP-1 and its cleavage products in diabetic db/db mice. Using an adeno-associated viral vector system, we overexpressed DPP-4-resistant GLP-1 (7-37 Mut8) and the two GLP-1 cleavage products, GLP-1 (9-37) and GLP-1 (28-37), in diabetic db/db mice. Only GLP-1 (7-37 Mut8), but none of the cleavage products, significantly improved glucose metabolism. Still, all GLP-1 constructs significantly reduced tubulointerstitial renal damage, lowered expression of the tubular injury markers, and attenuated renal accumulation of macrophages and T cells. This was associated with a systemic immunomodulatory effect, which was similarly found in an acute renal ischemia/reperfusion injury model. In conclusion, GLP-1 cleavage products proved sufficient to mediate organ-protective effects, which might help to explain differences between GLP-1 receptor agonists.
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PMID:Glucagon-Like Peptide 1 and Its Cleavage Products Are Renoprotective in Murine Diabetic Nephropathy. 3016 5

Acute kidney injury (AKI) is common in patients with sepsis and causes renal ischemia. Glucagon-like peptide-1 (GLP-1) protects the vascular system and the kidney, and GLP-1 receptor (GLP-1R) is expressed in the kidney. Renal GLP-1R activity is decreased in chronic kidney disease (CKD), but is increased by the inflammatory response; however, the effect of AKI on GLP-1R expression is unknown. We investigated the role of GLP-1 by assessing GLP-1R expression in the renal cortex in animals with AKI-related sepsis, CKD, and CKD-with-sepsis. We generated a model of CKD by 5/6 nephrectomy, and sepsis induced by cecal perforation, in male Sprague-Dawley rats. We compared renal GLP-1R expression at 3, 6, 12, 24, and 72 h after cecal perforation, and in CKD and CKD-with-sepsis. We performed blood and urine tests, western blotting (WB), and immunohistochemistry (IHC) to assay GLP-1R expression in renal tubules. The CKD-with-sepsis group showed the lowest kidney function, urine volume, and serum glucose and albumin levels. GLP-1R expression in renal tubules was decreased at 3 h, increased at 24 h, and decreased at 72 h after sepsis induction. GLP-1R expression was decreased at 8 weeks after CKD and was lowest in the CKD-with-sepsis group. The WB results were verified against those obtained by IHC. GLP-1R expression in renal tubules is increased in early sepsis, which may explain the protective effect of endogenous GLP-1 against sepsis-related inflammation.
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PMID:Renal Tubular Glucagon-Like Peptide-1 Receptor Expression Is Increased in Early Sepsis but Reduced in Chronic Kidney Disease and Sepsis-Induced Kidney Injury. 3179 76