Although vasopressin V receptor (VR) mRNA has been detected in the kidney, the precise renal localization as well as pharmacological and physiological properties of this receptor remain unknown. Using the selective V agonist d[Leu, Lys]VP, either fluorescent or radioactive, we showed that VR is mainly present in principal cells of the inner medullary collecting duct (IMCD) in the male rat kidney. Protein and mRNA expression of VR were very low compared with the V receptor (VR).
View Article and Find Full Text PDFThis review addresses the physiological role of the kallikrein-kinin system in arteries, heart and kidney and the consequences of kallikrein and kinin actions in diseases affecting these organs, especially ischemic and diabetic diseases. Emphasis is put on pharmacological and genetic studies targeting kallikrein; ACE/kininase II; and the two kinin receptors, B1 (B1R) and B2 (B2R), distinguished through the work of Domenico Regoli and his collaborators. Potential therapeutic interest and limitations of the pharmacological manipulation of B1R or B2R activity in cardiovascular and renal diseases are discussed.
View Article and Find Full Text PDFBile acids (BAs) regulate dietary lipid hydrolysis and absorption in the proximal intestine. Several studies have highlighted a determinant role of circulating levels and/or metabolism of BAs in the pathogenesis of major cardiometabolic diseases. Whether changes in BA profiles are causative or are consequence of these diseases remains to be determined.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
February 2020
The thick ascending limb of the loop of Henle (TAL) is the first segment of the distal nephron, extending through the whole outer medulla and cortex, two regions with different composition of the peritubular environment. The TAL plays a critical role in the control of NaCl, water, acid, and divalent cation homeostasis, as illustrated by the consequences of the various monogenic diseases that affect the TAL. It delivers tubular fluid to the distal convoluted tubule and thereby affects the function of the downstream tubular segments.
View Article and Find Full Text PDFKallikrein-K1 is the main kinin-forming enzyme in organs in resting condition and in several pathological situations whereas angiotensin I-converting enzyme/kininase II (ACE) is the main kinin-inactivating enzyme in the circulation. Both ACE and K1 activity levels are genetic traits in man. Recent research based mainly on human genetic studies and study of genetically modified mice has documented the physiological role of K1 in the circulation, and also refined understanding of the role of ACE.
View Article and Find Full Text PDFDiabetes Res Clin Pract
December 2018
Glucagon secretion is stimulated by a low plasma glucose concentration. By activating glycogenolysis and gluconeogenesis in the liver, glucagon contributes to maintain a normal glycemia. Glucagon secretion is also stimulated by the intake of proteins, and glucagon contributes to amino acid metabolism and nitrogen excretion.
View Article and Find Full Text PDFBackground: The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function.
View Article and Find Full Text PDFPlasma potassium concentration (P ) is tightly regulated. Insulin is known to favor potassium entry into cells. But how potassium leaves the cells later on is not often considered.
View Article and Find Full Text PDFMany experimental protocols in rodents require the comparison of groups that are fed different diets. Changes in dietary electrolyte and/or fat content can influence food intake, which can potentially introduce bias or confound the results. Unpalatable diets slow growth or cause weight loss, which is exacerbated by housing the animals in individual metabolic cages or by surgery.
View Article and Find Full Text PDFPurpose: High plasma copeptin, a marker of vasopressin, predicts diabetes mellitus. We tested if copeptin could be suppressed by increased water intake in healthy individuals, and if a water-induced change in copeptin was accompanied by altered concentrations of glucose, insulin or glucagon.
Methods: Thirty-nine healthy individuals underwent, in random order, 1 week of high water intake (3 L/day on top of habitual intake) and 1 week of normal (habitual) fluid intake (control).
Angiotensin I-converting enzyme (ACE) levels in humans are under strong genetic influence. Genetic variation in ACE has been linked to risk for and progression of cardiovascular and renal diseases. Causality has been documented in genetically modified mice, but the mechanisms underlying causality are not completely elucidated.
View Article and Find Full Text PDFActivation of the kallikrein-kinin system enhances cardiac and renal tolerance to ischemia. Here we investigated the effects of selective agonists of kinin B1 or B2 receptor (R) in brain ischemia-reperfusion in diabetic and non-diabetic mice. The role of endogenous kinins was assessed in tissue kallikrein deficient mice (TK).
View Article and Find Full Text PDFGenerally, eating salty food items increases thirst. Thirst is also stimulated by the experimental infusion of hypertonic saline. But, in steady state, does the kidney need a higher amount of water to excrete sodium on a high than on a low sodium intake? This issue is still controversial.
View Article and Find Full Text PDFAims: Vasopressin is increased in diabetes and was shown to contribute to development of diabetic nephropathy through V2 receptor (V2R) activation in an experimental model of type 1 diabetes. The role of V2R in type 2 diabetes remains undocumented. This study addresses the issue in a mouse model of type 2 diabetes.
View Article and Find Full Text PDFRecent epidemiological studies have revealed novel relationships between low water intake or high vasopressin (AVP) and the risk of hyperglycemia and diabetes. AVP V and V receptors (R) are expressed in the liver and pancreatic islets, respectively. The present study was designed to determine the impact of different levels of circulating AVP on glucose homeostasis in normal Sprague-Dawley rats, as well as the respective roles of VR and VR.
View Article and Find Full Text PDFObjective: Plasma copeptin, a surrogate for vasopressin, has been associated with a decline in renal function and albuminuria in population-based studies as well as with progression of diabetic nephropathy in people with type 2 diabetes. We assessed the risk of kidney and coronary events and all-cause mortality associated with plasma copeptin in people with type 1 diabetes.
Research Design And Methods: Plasma copeptin was measured in baseline samples of the GENEDIAB (n = 398; 56% male; mean ± SD age 45 ± 12 years and diabetes duration 28 ± 10 years) and GENESIS (n = 588; 52% male; age 42 ± 11 years; diabetes duration 27 ± 9 years) cohorts.
Genetic and pharmacological studies, clinical and experimental, focused on kallikrein-K1, kinin receptors and ACE/kininase II suggest that kinin release in the settings of ischemia or diabetes reduces organ damage, especially in the heart and kidney. Kinin bioavailability may be a limiting factor for efficacy of current kinin-potentiating drugs, like ACE inhibitors. Primary activation of kinin receptors by prototypic pharmacological agonists, peptidase-resistant, selective B1 or B2, displays therapeutic efficacy in experimental cardiac and peripheral ischemic and diabetic diseases.
View Article and Find Full Text PDFAm J Physiol Renal Physiol
August 2016
It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function.
View Article and Find Full Text PDFWe performed a comprehensive literature review to examine evidence on the effects of hydration on the kidney. By reducing vasopressin secretion, increasing water intake may have a beneficial effect on renal function in patients with all forms of chronic kidney disease (CKD) and in those at risk of CKD. This potential benefit may be greater when the kidney is still able to concentrate urine (high fluid intake is contraindicated in dialysis-dependent patients).
View Article and Find Full Text PDFContext: Experimental data support a role for vasopressin in metabolic disorders.
Objective: We investigated associations of plasma copeptin, a surrogate of vasopressin, and of allelic variations in the arginine vasopressin-neurophysin II gene with insulin secretion, insulin sensitivity, and the risk for impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM).
Design, Setting, And Participants: We studied 5110 unrelated French men and women from a prospective cohort of the general population (Data from Epidemiological Study on the Insulin Resistance Syndrome cohort, 9-y follow-up).
The ability to produce hyperosmotic urine allows mammals, including humans, to excrete their soluble mineral and organic waste products in the urine with a limited amount of water. The urinary concentrating capacity depends primarily on a special "loop-shaped" architecture of the nephrons and vessels, observed only in mammals. It also depends on the influence of antidiuretic hormone on the permeability to water of the collecting ducts on their entire length, and on the permeability to urea limited to the terminal portion of these ducts in the inner medulla.
View Article and Find Full Text PDFImpaired skin wound healing is a major medical problem in diabetic subjects. Kinins exert a number of vascular and other actions limiting organ damage in ischaemia or diabetes, but their role in skin injury is unknown. We investigated, through pharmacological manipulation of bradykinin B1 and B2 receptors (B1R and B2R respectively), the role of kinins in wound healing in non-diabetic and diabetic mice.
View Article and Find Full Text PDFBackground/aims: In recent days, chronic kidney disease (CKD) is becoming an increasing public health problem. Identification of factors contributing to its progression is crucial for designing preventive interventions. Previous studies suggested that chronically high vasopressin is deleterious to the renal function.
View Article and Find Full Text PDFBackground: Several experimental studies in rats and a few association studies in humans suggest that the antidiuretic action of vasopressin may accelerate the progression of chronic kidney disease. We undertook a retrospective analysis in a monocentric cohort of 273 patients with chronic kidney disease stages 1-4, focusing on a strong variable of interest, urinary osmolarity, and a strong endpoint, dialysis initiation. Data was analyzed in a multivariate proportional sub-distribution hazards model for competing risk data with appropriate co-variates.
View Article and Find Full Text PDFProduction of adrenomedullin (ADM), a vasodilator peptide, increases in response to ischemia and hypoxia in the vascular wall and the kidney. This may be an adaptive response providing protection against organ damage. We investigated the hypothesis that ADM has a nephroprotective effect in two prospective cohorts of patients with type 2 diabetes recruited in France.
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