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

Abstract

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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“…This was based on earlier reports demonstrating L-arginine to be effective against renal toxic or ischemic injury (33)(34)(35)(36)(37)(38)(39). L-Arginine supplementation significantly improved BUN (p < 0.01)) and serum creatinine (p < 0.05) clearance, as shown in Figure 5A and B, respectively.…”

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“…Plasma glucagon levels are abnormally elevated in both T1D and T2D subjects, indicating that a-cell hypersecretion is a common diabetic feature [196][197][198][199]. Abnormally high fasting glucagon levels, suggestive of a-cell hypersecretion, have been found also in normoglycemic insulin-resistant obese adults and adolescents [200][201][202][203][204]. In the latter group, high fasting glucagon levels were observed in the face of elevated fasting insulin levels, suggesting that a-cells manifested insulin resistance to the suppressive effect of insulin on glucagon secretion.…”

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