The effect of short-term glucagon infusion on kidney function in normal man

Parving, Hans‐Henrik; Noer, J; Kehlet, Henrik; Mogensen, Carl Erik; Svendsen, P.; Heding, L. G.

doi:10.1007/bf01223273

Cited by 93 publications

(44 citation statements)

References 10 publications

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“…This evidence may suggest that glucagon can haemodynamically in¯uence both selective (low molecular weight) and non selective (high molecular weight) proteinuria, potentially increasing the risk to develop focal of diffuse glomerulosclerosis and kidney disease in central obesity. 39,40 In agreement with previous studies, 14,42 the increase of urinary excretion of a1 microglobulin, found in patients with CO, suggests that glucagon can negatively in¯uence the tubular reabsorption if proteins. Obesity with central body fat distribution might therefore represent a risk to develop proteinuria also with a tubular mechanism.…”

Section: Discussionsupporting

confidence: 90%

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

et al. 1999

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OBJECTIVES: Insulin-resistance syndrome and hyperinsulinaemia are linked with cardiovascular disease (CVD) in the obese population. In particular, cardiovascular risk is more frequent in central obesity and is associated with microalbuminuria (MA). MA and changes of glomerular permeability to proteins in obesity might be related with renal haemodynamic modi®cations (that is glomerular hyper®ltration). Since glucagon is physiologically involved in renal haemodynamic regulation, the purpose of this study was to examine whether changes of circulating glucagon levels might haemodynamically induce MA and proteinuria in patients with central obesity. SUBJECTS: Forty normotensive obese out-patients, 22 with central (CO group) and 18 with peripheral (PO group) body fat distribution and 11 healthy subjects. MEASUREMENTS:Serum insulin and glucagon concentrations (fasting and after oral glucose tolerance test (OGTT)) by radio immuno assay (RIA); glomerular ®ltration rate (GFR, isotopic); total clearances and urinary excretion rates of albumin (AER), IgG (IgGER) and a a1 microglobulin (computerized immunonephelometry). RESULTS: GFR and insulin concentrations (fasting and during OGTT) were higher in the CO than the PO group. Fasting glucagon concentrations were increased, and not physiologically suppressed during OGTT in patients with CO (fasting, P`0.05; OGTT 60 and 120 min, P`0.001 vs PO group). Moreover, glucagon concentrations were signi®cantly correlated with GFR in the CO group (fasting, r 0.49, P`0.05; 60 min after OGTT, r 0.58, P`0.01); whereas no correlations were found in the PO group. Higher AER (P`0.001), IgGER (P`0.001) and a1 microglobulin (P`0.05) urinary concentrations were found in patients with CO than in the PO group. CONCLUSIONS: The increase of serum glucagon concentrations may be associated with the enhancement of GFR in patients with central obesity. Glomerular hyper®ltration might in¯uence the development of MA and of proteinuria by means of a haemodynamic mechanism so contributing to increase the risk of renal microvascular complications and of CVD in central obesity.

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Section: Discussionsupporting

confidence: 90%

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

et al. 1999

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“…We, therefore, have tested IDDM patients under (near) normoglycaemic conditions both at BL and after stimulation (S). A reasonably well-controlled group of patients was chosen in order to alleviate as much as possible the influence of hormones, the levels of which can change during periods of poor metabolic control and influence GFR: growth hormone and growth factors [15], glucagon [16,17], and ketone bodies [18,19],…”

Section: Introductionmentioning

confidence: 99%

Renal Function and Renal Function Reserve in Insulin-Dependent Diabetic Patients during (Near) Normoglycaemia

Bilo

Ballegooie

Hazenberg

et al. 1991

Nephron

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Twenty-three normoalbuminuric (N) and 7 microalbuminuric (M) insulin-dependent diabetes mellitus (IDDM) patients were studied under (near) normoglycaemic conditions. They were reasonably well controlled during the period preceding the renal function test (HbA₁: N = 7.6 ± 1.3%, M = 8.0 ± 2.2%; normal < 6.0%). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured using the clearances of ¹²⁵I-thalamate and ¹³¹I-hippuran, respectively. The renal reserve filtration capacity (RRFC) was tested by using a combination of a liquid mixed meal and an amino acid infusion. Blood glucose levels were kept as constant as possible throughout the testing procedure, both under baseline (BL) conditions and after stimulation (S). Under such (near) normoglycaemic conditions, no BL GFR values exceeding 150 ml/min/1.73 m² could be established. Furthermore, a RRFC could be established in all patients. Both groups showed a comparatively larger increase in GFR (N 13.0 ± 3.8%, M 10.8 ± 3.6%) than in ERPF (N 4.8 ± 7.0%, M 2.2 ± 5.8%; %Δ GFR vs. % ΔERPF p < 0.01), resulting in a higher filtration fraction (FF) during stimulation (N: BL FF 0.25 ± 0.03 vs. S FF 0.27 ± 0.03, p < 0.0l; M: BL FF 0.25 ± 0.01 vs. S FF 0.27 ± 0.01, p < 0.05). This suggests afferent vasodilation during stimulation in these (near) normoglycaemic, reasonably well-controlled IDDM patients, a situation comparable to that in non-diabetic subjects. Thus, reasonably well-controlled normoglycaemic N or M IDDM patients appear to have a (virtually) normal renal function, a normal renal vascular reactivity, and a normal RRFC. In our opinion, these results emphasize the importance of strict metabolic control in IDDM patients to prevent continuous afferent vasodilation and hyperfiltration.

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“…Infusion of glucagon can produce a rise in glomerular filtration rate (GFR) and renal plasma flow (RPF), although supraphysiological doses have usually been administered (40,41). In addition, a previous study suggested that people with diabetes may have an enhanced glomerular hyperfiltration response to glucagon infusion (40).…”

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confidence: 99%

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

Puhlman

Cooney

Short

2002

American Journal of Physiology-Renal Physiology

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Increased dietary protein and circulating amino acids raise glomerular filtration rate (GFR) and pressure. In diabetes, this glomerular hyperfiltration response is augmented. The purpose of this study was to determine whether glucagon mediates the augmented GFR response to amino acids in diabetes and whether the responses to amino acids and glucagon depend on prostaglandins. Patients with type 1 diabetes mellitus ( n = 12) and normal control subjects ( n= 12) were studied in a series of six experiments, each on different occasions. Baseline GFR was not significantly increased, but filtration fraction was higher in diabetes. In response to amino acid infusion, GFR increased more and filtration fraction was greater among those with diabetes. Their augmented GFR response to amino acids was not inhibited by octreotide or indomethacin. Participants with diabetes also had enhanced GFR and renal plasma flow responses to glucagon infusion, both of which were inhibited by indomethacin. Glomerular hyperfiltration responses induced by amino acids or glucagon occur by divergent pathways in diabetes; only the response to glucagon is prostaglandin dependent.

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The effect of short-term glucagon infusion on kidney function in normal man

Cited by 93 publications

References 10 publications

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

Serum glucagon concentration and hyperinsulinaemia influence renal haemodynamics and urinary protein loss in normotensive patients with central obesity

Renal Function and Renal Function Reserve in Insulin-Dependent Diabetic Patients during (Near) Normoglycaemia

Effects of amino acids and glucagon on renal hemodynamics in type 1 diabetes

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