Glomerular Filtration Rate and Renal Plasma Flow in Normal and Diabetic Man during Elevation of Blood Sugar Levels

Mogensen, Carl Erik

doi:10.3109/00365517109086898

Cited by 72 publications

(40 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increase in the glomerular filtration rate (GFR), also known as glomerular hyperfiltration, is one of the important functional abnormalities in diabetic kidneys (37). To clarify whether troglitazone could prevent glomerular hyperfiltration in diabetic rats, we evaluated GFR and renal plasma flow (RPF) by measuring the renal clearance of inulin and PAH, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…First, troglitazone prevented glomerular hyperfiltration. Glomerular hyperfiltration found in the early phase of type 1 diabetes has been postulated to be related to the subsequent development of diabetic nephropathy (37). Multiple factors have been reported to be involved in the development of glomerular hyperfiltration (42), some of which might be associated with the activation of the PKC-ERK pathway.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats.

et al. 2000

View full text Add to dashboard Cite

Thiazolidinedione (TZD) compounds are widely used as oral hypoglycemic agents. Herein, we provide evidence showing that troglitazone, one of the TZD compounds, is able to prevent glomerular dysfunction in diabetic rats through a novel mechanism independent of its insulin-sensitizing action. We examined the effect of troglitazone on functional and biochemical parameters of glomeruli in streptozotocin-induced diabetic rats. Troglitazone was able to prevent not only diabetic glomerular hyperfiltration and albuminuria, but an increase in mRNA expression of extracellular matrix proteins and transforming growth factor-␤1 in glomeruli of diabetic rats, without changing blood glucose levels. Biochemically, an increase in diacylglycerol (DAG) contents and the activation of the protein kinase C (PKC)-extracellular signal-regulated kinase (ERK) pathway in glomeruli of diabetic rats were abrogated by troglitazone. The activation of DAG-PKC-ERK pathways in vitro in mesangial cells cultured under high glucose conditions was also inhibited by troglitazone. Troglitazone enhanced the activities of DAG kinase, which could metabolize DAG to phosphatidic acid, in both glomeruli of diabetic rats and mesangial cells cultured under high glucose conditions. Surprisingly, pioglitazone, another TZD compound without ␣-tocopherol moiety in its structure, also prevented the activation of the DAG-PKC pathway and activated DAG kinase in mesangial cells cultured under high glucose conditions. These results may identify the TZDs as possible new therapeutic agents for diabetic nephropathy that prevent glomerular dysfunction through the inhibition of the DAG-PKC-ERK pathway. Diabetes 49:1022-1032, 2000 T hiazolidinediones (TZDs), novel insulin-sensitizing agents, have been shown to attenuate hyperinsulinemia and hyperglycemia in insulin-resistant diabetic animals and human subjects with type 2 diabetes (1,2). These agents are currently in clinical trials and have been widely used as oral antidiabetic agents in subjects with type 2 diabetes in the U.S. and other countries. Although it is generally believed that TZDs exert insulin-sensitizing activity through the activation of peroxisome proliferator-activated receptor (PPAR)-␥, a member of the PPAR nuclear receptor superfamily (3), the exact mechanism of their action remains to be clarified (4-6). Besides its insulinsensitizing activity, troglitazone, one of the TZD compounds, was found to inhibit high glucose-induced proliferation and migration of vascular smooth muscle cells by inhibiting the activation of protein kinase C (PKC) (7); to inhibit platelet aggregation (8); to reduce balloon injury-induced intimal hyperplasia in rat artery (9); and to suppress both insulin-and angiotensin II-induced increase of DNA synthesis by inhibiting the activation of extracellular signal-regulated kinase (ERK) (10,11). Troglitazone was also shown to ameliorate albuminuria and peripheral neuropathy in streptozotocin (STZ)-induced diabetic rats, regardless of blood glucose levels (12,13). These results indicate ...

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats.

et al. 2000

View full text Add to dashboard Cite

show abstract

“…It is now accepted by most that hyperfiltration and the degree of microalbuminuria are indicators of established diabetic nephropathy (15,16). It is also accepted that any reduction of microalbuminuria may be beneficial for kidney function.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone Improves Glomerular Hyperfiltration, Renal Endothelial Dysfunction, and Microalbuminuria of Incipient Diabetic Nephropathy in Patients

et al. 2005

View full text Add to dashboard Cite

Microalbuminuria, an early feature of diabetic nephropathy, indicates intrarenal endothelial damage. In type 2 diabetes, microalbuminuria is strongly related to insulin resistance. We therefore investigated whether rosiglitazone, an insulin-sensitizing drug that is known to improve endothelial dysfunction, was able to improve intrarenal endothelial dysfunction and microalbuminuria. Nineteen type 2 diabetic patients participated in this double-blind cross-over trial. Nine patients with newly diagnosed disease without microalbuminuria were randomized to a treatment with rosiglitazone or nateglinide, each for 12 weeks. Ten patients with microalbuminuria were randomized to rosiglitazone or placebo, each for 12 weeks in addition to their previous antidiabetic medication. After each treatment, glomerular filtration rate (GFR), renal plasma flow, and filtration fraction were measured before and after blockade of nitric oxide (NO) by intravenous administration of N-monomethyl-L-arginine-acetate (L-NMMA). Ten healthy subjects served as control subjects. Type 2 diabetic patients at baseline showed glomerular hyperfiltration compared with healthy control subjects. Rosiglitazone reduced elevated GFR and filtration fraction toward control primarily in patients with microalbuminuria (GFR: 133.4 ؎ 9.8 vs. 119.6 ؎ 8.7 ml/min; filtration fraction: 23.2 ؎ 1.7 vs. 20.5 ؎ 1.6% before and after rosiglitazone, respectively; control subjects: GFR 111.7 ؎ 8.6 ml/min, filtration fraction 20.4 ؎ 1.5%). Rosiglitazone improved intrarenal NO bioavailability in type 2 diabetes toward control as shown by infusion of L-NMMA. Rosiglitazone reduced albumin excretion in type 2 diabetes with microalbuminuria from 116.5 ؎ 31 to 40.4 ؎ 12 mg/day. Rosiglitazone ameliorated glomerular hyperfiltration in early type 2 diabetes, improved NO bioavailability, and lessened renal end-organ damage in type 2 diabetes with microalbuminuria. Diabetes

show abstract

“…In experimental diabetes, high blood glucose causes high intraglomerular hydraulic pressure, glomerular filtration rate (GFR), and renal plasma flow, 7 just as in type 1 diabetes. 14 In the present study, changes in glomerular capillary pressure were therefore estimated from those in GFR, effective renal plasma flow (ERPF), and mean arterial pressure (MAP) produced by the transition from normoglycemia to hyperglycemia in type 1 diabetics selected for their genetic predisposition to low or high ACE levels. Thus, case subjects had the II genotype, and controls had the ID or DD genotype.…”

mentioning

confidence: 99%

Renal Changes on Hyperglycemia and Angiotensin-Converting Enzyme in Type 1 Diabetes

Marre

Bouhanick²,

Berrut³

et al. 1999

Hypertension

View full text Add to dashboard Cite

Abstract-Hyperglycemia causes capillary vasodilation and high glomerular capillary hydraulic pressure, which lead to glomerulosclerosis and hypertension in type 1 diabetic subjects. The insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene can modulate risk of nephropathy due to hyperglycemia, and the II genotype (producing low plasma ACE concentrations and probably reduced renal angiotensin II generation and kinin inactivation) may protect against diabetic nephropathy. We tested the possible interaction between ACE I/D polymorphism and uncontrolled type 1 diabetes by measuring glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) during normoglycemia (Ϸ5 mmol/L) and hyperglycemia (Ϸ15 mmol/L) in 9 normoalbuminuric, normotensive type 1 diabetic subjects with the II genotype and 18 matched controls with the ID or DD genotype. Baseline GFR (145Ϯ22 mL/min per 1.73 m 2 ) and ERPF (636Ϯ69 mL/min per 1.73 m 2 ) of II subjects declined by 8Ϯ10% and 10Ϯ9%, respectively, during hyperglycemia; whereas baseline GFR (138Ϯ16 mL/min per 1.73 m 2 ) and ERPF (607Ϯ93 mL/min per 1.73 m 2 ) increased by 4Ϯ7% and 6Ϯ11%, respectively, in ID and DD subjects (II versus ID or DD subjects: Pϭ0.0007 and Pϭ0.0005, for GFR and ERPF, respectively). The changes in renal hemodynamics of subjects carrying 1 or 2 D alleles were compatible, with a mainly preglomerular vasodilation induced by hyperglycemia, proportional to plasma ACE concentration (Pϭ0.024); this was not observed in subjects with the II genotype. Thus, type 1 diabetic individuals with the II genotype are resistant to glomerular changes induced by hyperglycemia, providing a basis for their reduced risk of nephropathy. (Hypertension. 1999;33:775-780.)

show abstract

Glomerular Filtration Rate and Renal Plasma Flow in Normal and Diabetic Man during Elevation of Blood Sugar Levels

Cited by 72 publications

References 8 publications

Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats.

Thiazolidinedione compounds ameliorate glomerular dysfunction independent of their insulin-sensitizing action in diabetic rats.

Rosiglitazone Improves Glomerular Hyperfiltration, Renal Endothelial Dysfunction, and Microalbuminuria of Incipient Diabetic Nephropathy in Patients

Renal Changes on Hyperglycemia and Angiotensin-Converting Enzyme in Type 1 Diabetes

Contact Info

Product

Resources

About