Diabetes‐induced hyperfiltration in adenosine A1‐receptor deficient mice lacking the tubuloglomerular feedback mechanism

Sällström, Johan; Carlsson, Per‐Ola; Fredholm, Bertil B.; Larsson, Erik; Persson, A. Erik G.; Palm, Fredrik

doi:10.1111/j.1748-1716.2007.01705.x

Cited by 62 publications

(34 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In such a case, some degree of hyperfiltration would persist in the absence of A 1 Rs while the macula densa salt would convert from subnormal to supranormal. While distal salt delivery has not been measured in A 1 R–/– diabetic mice and A 1 R–/– diabetic mice did not hyperfilter in our hands, two other studies have reported hyperfiltration in A 1 R–/– diabetic mice [29, 30]. However, in one study the nondiabetic A 1 R–/– but not the alloxan-diabetic A 1 R–/– mice were hypotensive compared with their WT controls during measurements of GFR [29].…”

Section: Discussionmentioning

confidence: 59%

“…While distal salt delivery has not been measured in A 1 R–/– diabetic mice and A 1 R–/– diabetic mice did not hyperfilter in our hands, two other studies have reported hyperfiltration in A 1 R–/– diabetic mice [29, 30]. However, in one study the nondiabetic A 1 R–/– but not the alloxan-diabetic A 1 R–/– mice were hypotensive compared with their WT controls during measurements of GFR [29]. This is in contrast to two previous reports on the same mouse strain, which concluded that blood pressure under isoflurane anesthesia as well as in conscious mice is higher in A 1 R–/– compared with WT control mice [21, 31].…”

Section: Discussionmentioning

confidence: 59%

See 1 more Smart Citation

Adenosine A1 Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes Mellitus

Vallon

Schroth²,

Satriano³

et al. 2009

Nephron Physiol

View full text Add to dashboard Cite

Background: In early type 1 diabetes mellitus, changes in proximal reabsorption influence glomerular filtration rate (GFR) through tubuloglomerular feedback (TGF). Due to TGF, a primary increase in proximal reabsorption causes early diabetic hyperfiltration, while a heightened sensitivity of the proximal tubule to dietary salt leads to the so-called salt paradox, where a change in dietary salt causes a reciprocal change in GFR (‘tubulocentric principle’). Here, experiments were performed in adenosine A₁ receptor knockout mice (A₁R–/–), which lack an immediate TGF response, to determine whether A₁Rs are essential for early diabetic hyperfiltration and the salt paradox. Methods: GFR was measured by inulin disappearance in conscious A₁R–/– and wild-type (WT) mice after 4 weeks of streptozotocin diabetes on a control NaCl diet (1%), and measurements were repeated after 6 days of equilibration on a low-NaCl (0.1%) or a high-NaCl (4%) diet. Results: A₁R–/– and WT were similar with respect to blood glucose, dietary intakes and body weight changes on a given diet. Diabetic hyperfiltration occurred in WT, but was blunted in A₁R–/–. A reciprocal relationship between GFR and dietary salt was found in WT diabetics, but not A₁R–/– diabetics or nondiabetics of either strain. Conclusion: A₁Rs determine glomerular hyperfiltration and the salt paradox in early diabetes, which is consistent with the tubulocentric principle.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 59%

Adenosine A1 Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes Mellitus

Vallon

Schroth²,

Satriano³

et al. 2009

Nephron Physiol

View full text Add to dashboard Cite

show abstract

“…However, diabetes-induced glomerular hyperfiltration has been shown to occur in mice deficient in the adenosine receptor A 1 , which lack the tubuloglomerular feedback mechanism. 44 Further studies are therefore needed to determine whether the mechanisms proposed in the etiology of glomerular hyperfiltration in animal models can be applied to human patients with diabetes. 28 Interestingly, increased proximal tubular sodium reabsorption has also been demonstrated in obese individuals without diabetes but was thought to be a consequence rather than a cause of glomerular hyperfiltration because the increased filtration fraction increases postglomerular oncotic pressure and therefore favors sodium reabsorption.…”

Section: Glomerular Hyperfiltration In Diabetesmentioning

confidence: 98%

Glomerular hyperfiltration: definitions, mechanisms and clinical implications

et al. 2012

View full text Add to dashboard Cite

Glomerular hyperfiltration is a phenomenon that can occur in various clinical conditions including kidney disease. No single definition of glomerular hyperfiltration has been agreed upon, and the pathophysiological mechanisms, which are likely to vary with the underlying disease, are not well explored. Glomerular hyperfiltration can be caused by afferent arteriolar vasodilation as seen in patients with diabetes or after a high-protein meal, and/or by efferent arteriolar vasoconstriction owing to activation of the renin-angiotensin-aldosterone system, thus leading to glomerular hypertension. Glomerular hypertrophy and increased glomerular pressure might be both a cause and a consequence of renal injury; understanding the renal adaptations to injury is therefore important to prevent further damage. In this Review, we discuss the current concepts of glomerular hyperfiltration and the renal hemodynamic changes associated with this condition. A physiological state of glomerular hyperfiltration occurs during pregnancy and after consumption of high-protein meals. The various diseases that have been associated with glomerular hyperfiltration, either per nephron or per total kidney, include diabetes mellitus, polycystic kidney disease, secondary focal segmental glomerulosclerosis caused by a reduction in renal mass, sickle cell anemia, high altitude renal syndrome and obesity. A better understanding of the mechanisms involved in glomerular hyperfiltration could enable the development of new strategies to prevent progression of kidney disease.

show abstract

“…131 Hyperfiltration was higher in Ins2 +/-Akita diabetic mice that lacked A 1 adenosine receptors than in wild-type mice; 132 however, no differences in glomerular filtration between alloxan-induced diabetic A 1 adenosine receptor knockout and wild-type mice were observed. 133 Infiltration of macrophages (mediated by the release of lysosomal enzymes) and production of nitric oxide, reactive oxygen species, transforming growth factor β (TGF-β), TNF and IL-1, have pivotal roles in the develop ment and progression of diabetic nephropathy. 134 The A 2A adenosine receptor agonist ATL-146e protects against diabetic nephropathy in rats with streptozotocin-induced diabetes mellitus by reducing glomerular inflammation; 135 activation of A 2A adenosine receptors reduced the infiltration of macrophages, with consequent decreases in the urinary levels of several proinflammatory cytokines, such as TNF, monocyte chemoattractant protein 1 and IFN-γ.…”

Section: Diabetic Nephropathymentioning

confidence: 99%

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

et al. 2015

View full text Add to dashboard Cite

Adenosine is a key extracellular signalling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors, A1, A2A, A2B and A1 adenosine receptors. Accumulating evidence highlights a critical role for the adenosine system in the regulation of glucose homeostasis and the pathophysiology of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Although adenosine signalling is known to affect insulin secretion, new data indicate that adenosine signalling also contributes to the regulation of β-cell homeostasis and activity by controlling the proliferation and regeneration of these cells as well as the survival of β cells in inflammatory microenvironments. Furthermore, adenosine is emerging as a major regulator of insulin responsiveness by controlling insulin signalling in adipose tissue, muscle and liver; adenosine also indirectly mediates effects on inflammatory and/or immune cells in these tissues. This Review critically discusses the role of the adenosine-adenosine receptor system in regulating both the onset and progression of T1DM and T2DM, and the potential of pharmacological manipulation of the adenosinergic system as an approach to manage T1DM, T2DM and their associated complications.

show abstract

Diabetes‐induced hyperfiltration in adenosine A₁‐receptor deficient mice lacking the tubuloglomerular feedback mechanism

Cited by 62 publications

References 24 publications

Adenosine A<sub>1</sub> Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes Mellitus

Adenosine A<sub>1</sub> Receptors Determine Glomerular Hyperfiltration and the Salt Paradox in Early Streptozotocin Diabetes Mellitus

Glomerular hyperfiltration: definitions, mechanisms and clinical implications

Adenosine signalling in diabetes mellitus—pathophysiology and therapeutic considerations

Contact Info

Product

Resources

About