Renal hemodynamic response to l-arginine in uncomplicated, type 1 diabetes mellitus: the role of buffering anions and tubuloglomerular feedback

2012 ◽  
Vol 303 (5) ◽  
pp. F648-F658 ◽  
Author(s):  
Alberto Montanari ◽  
Almerina Biggi ◽  
Aderville Cabassi ◽  
Irene Pelloni ◽  
Filippo Pigazzani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Filtration Rate ◽  
Critical Role ◽  
Hemodynamic Response ◽  
Tubuloglomerular Feedback ◽  
Critical Determinant ◽  
Renal Hemodynamic ◽  
Type 1 Dm

According to the “tubulocentric” hypothesis of the glomerular hyperfiltration of diabetes mellitus (DM), tubuloglomerular feedback (TGF) is the critical determinant of the related renal hemodynamic dysfunction. To examine the role of TGF in human type 1 DM, 12 salt-replete healthy (C) and 11 uncomplicated DM individuals underwent measurements of glomerular filtration rate (GFR), renal blood flow (RBF), and lithium-derived absolute “distal” sodium delivery (DDNa). Measurements were made during two 3-h infusions of 0.012 mmol·kg−1·min−1 l-arginine (ARG) buffered with either equimolar HCl (ARG.HCl) or citric acid (ARG.CITR). Our hypothesis was that changes in TGF signaling would be directionally opposite ARG.HCl vs. ARG.CITR according to the effects of the ARG-buffering anion on DDNa. Similar changes in C and DM followed ARG.CITR, with declines in DDNa (−0.26 ± 0.07 mmol/min C vs. −0.31 ± 0.07 mmol/min DM) and increases in RBF (+299 ± 25 vs. +319 ± 29 ml·min−1·1.73 m−2) and GFR (+6.6 ± 0.8 vs. +11.6 ± 1.2 ml·min−1·1.73 m−2). In contrast, with ARG.HCl, DDNa rose in both groups ( P = 0.001), but the response was 73% greater in DM (+1.50 ± 0.15 mmol/min C vs. +2.59 ± 0.22 mmol/min DM, P = 0.001). RBF also increased ( P = 0.001, +219 ± 20 ml·min−1·1.73 m−2 C, +105 ± 14 DM), but ΔRBF after ARG.HCl was lower vs. ARG.CITR in both groups ( P = 0.001). After ARG.HCl, ΔRBF also was 50% lower in DM vs. C ( P = 0.001) and GFR, unchanged in C, declined in DM (−7.4 ± 0.9 ml·min−1·1.73 m−2, P = 0.02 vs. C). After ARG.HCl, unlike ARG.CITR, DDNa increased in C and DM, associated with less ΔRBF and ΔGFR vs. ARG.CITR. This suggests that the renal hemodynamic response to ARG is influenced substantially by the opposite actions of HCl vs. CITR on DDNa and TGF. In DM, the association of ARG.HCl-induced exaggerated ΔDDNa, blunted ΔRBF, and the decline in GFR vs. C shows an enhanced TGF dependence of renal vasodilatation to ARG, in agreement with a critical role of TGF in DM-related renal hemodynamic dysfunction.

The effect of sex on humanin levels in healthy adults and patients with uncomplicated type 1 diabetes mellitus

2015 ◽  
Vol 93 (4) ◽  
pp. 239-243 ◽  
Author(s):  
Yuliya Lytvyn ◽  
Junxiang Wan ◽  
Vesta Lai ◽  
Pinchas Cohen ◽  
David Z.I. Cherney
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Function ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Vascular Protection ◽  
Type 1 Dm ◽  
Future Work ◽  
Recent Experimental Work

Diabetes mellitus (DM) is associated with a loss of renal and vascular protection in women compared with men, but the responsible mechanisms are unclear. Recent experimental work implicated humanin (HN) as a novel cytoprotective hormone in DM. Our goal was to measure sex-related differences in HN levels in uncomplicated type 1 DM patients (T1D) and healthy controls (HC), as well as the interaction between HN, circulating neurohormones, and vascular function. Plasma HN, cGMP and aldosterone, blood pressure (BP), glomerular filtration rate, and effective renal plasma flow (inulin and para-aminohippurate) were measured in HC (11 men, 10 women) and T1D (23 men and 18 women) during clamped euglycemia (4–6 mmol·L–1). Plasma HN levels were generally lower in HC men by comparison with the women, but the differences were not statistically significant. In contrast, levels in the T1D men were higher compared with the T1D women (p = 0.026) and HC men (p < 0.0001). In the HC men, but not the women, HN correlated negatively with BP, but not with renal function, cGMP, or aldosterone. In the T1D men, HN negatively correlated with plasma cGMP. In the T1D women, HN did not correlate with neurohormones or vascular function. Future work should determine the role of HN in the pathogenesis of sex-related vascular function differences in DM.

Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus

2008 ◽  
Vol 294 (6) ◽  
pp. F1336-F1341 ◽  
Author(s):  
David Z. I. Cherney ◽  
James W. Scholey ◽  
Rania Nasrallah ◽  
Maria G. Dekker ◽  
Cameron Slorach ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Young Men ◽  
Cyclooxygenase 2 ◽  
Ang Ii ◽  
Men And Women ◽  
Renal Hemodynamic ◽  
Type 1 Dm

In experimental studies, cyclooxygenase 2 (COX2)-derived vasodilatory prostaglandins play a more prominent role in arterial vasoregulation in females. The gender-dependent effect of COX2 modulation in humans with type 1 diabetes mellitus (DM) is unknown. Accordingly, we examined the renal hemodynamic role of prostaglandins by assessing the response to COX2 inhibition in young men and women with type 1 DM. We also used a graded ANG II infusion to determine whether gender-based differences were mediated by effects of COX2 inhibition on the renin angiotensin system (RAS). We hypothesized that COX2 inhibition would be associated with preferential vasoconstriction in women and would augment their response to ANG II. Baseline renal function and the response to an ANG II infusion were assessed during clamped euglycemia, and again after COX2 inhibition (200 mg celecoxib daily for 14 days) in 12 men and 9 women after 1 wk on a controlled protein and sodium diet. COX2 inhibition was associated with increases in filtration fraction ( P = 0.045) and renal vascular resistance and a decline in renal blood flow ( P = 0.04) in women compared with men. Before COX2 inhibition, women exhibited a decline in glomerular filtration rate in response to ANG II. COX2 inhibition abolished this effect, whereas the response was not altered in men. In summary, COX2 inhibition was associated with hemodynamic effects that differed based on gender. The ANG II response suggests that with uncomplicated type 1 DM, prostaglandins may contribute to RAS-mediated gender differences. Our results are consistent with experimental data suggesting augmented female prostanoid dependence.

scholarly journals Protein kinase C (PKC) involved in enhancement of α1-adrenoceptor-mediated responses of the main pulmonary artery in rats with diabetes mellitus

2017 ◽  
Vol 8 (2) ◽  
pp. 287-292 ◽  
Author(s):  
I. V. Kizub ◽  
О. I. Kharchenko ◽  
O. S. Kostiuk ◽  
L. I. Ostapchenko ◽  
A. I. Soloviev
Keyword(s):  
Diabetes Mellitus ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Pulmonary Artery ◽  
Main Pulmonary Artery ◽  
Pulmonary Arteries ◽  
Kinase C ◽  
Type 1 Dm

Diabetes mellitus (DM) causes multiple dysfunctions including circulatory disorders such as cardiomyopathy, angiopathy, atherosclerosis and arterial hypertension. Moreover, DM can strongly affect pulmonary circulation, enhancing the wall thickness of the pulmonary arteries, changing their tone and contractility, and gas exchange in the lungs. It can lead to marked loss of lung function and respiratory efficiency. It is also known that protein kinase C (PKC) activity increases in DM and that PKC is involved in the mechanisms of DM-associated vascular complications. However, the effect of DM on pulmonary artery tone has been poorly investigated and the role of PKC in this remains unknown. The aim of this study was to investigate changes in contractility of pulmonary arteries in rats with DM and to determine the possible role of PKC in this process. Experimental type 1 DM was elicited in male Wistar rats by single streptozotocin (STZ, 65 mg/kg) injection. DM was verified by the presence of hyperglycaemia. The investigation was performed on the isolated rings of the main pulmonary arteries using the method of vascular tone registration. Phenylephrine (PhE, 0.1 nM – 1 mM) caused dose-dependent constriction of the pulmonary arteries. The pD2 (negative logarithm of the agonist concentration required for half-maximum response) of this constriction increased in rats with DM, however significant changes in amplitude of PhE-induced constriction were not observed. PKC inhibition with chelerythrine and staurosporine (1 µM) significantly shifted PhE the concentration-response curve to the right in intact diabetic vessels but had no effect on sensitivity to PhE in deendothelised diabetic vessels. Our data suggest that type 1 DM leads to enhancement in pulmonary artery α1-adrenoceptor-mediated contractility and PKC activity in the endothelium rather than in vascular SMCs is involved in this process. 

Role of nitric oxide in the renal hemodynamic response to a meat meal

1994 ◽  
Vol 267 (4) ◽  
pp. R1050-R1055 ◽  
Author(s):  
F. J. Salazar ◽  
A. Alberola ◽  
T. Nakamura ◽  
J. P. Granger
Keyword(s):  
Nitric Oxide ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Hemodynamic Response ◽  
Synthesis Inhibition ◽  
Renal Hemodynamic ◽  
Meat Meal ◽  
Induced Changes ◽  
Chronically Instrumented Dogs

Ingestion of a high-protein meat meal results in significant increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). The mechanism involved in this hemodynamic response to the meat meal has not yet been fully elucidated. The present study was designed to test the hypothesis that nitric oxide (NO) is involved in the renal hyperemic responses to a meat meal. To test this hypothesis, renal hemodynamic response to a meat meal (10 g/kg) was determined in conscious, chronically instrumented dogs with (n = 9) and without (n = 7) an intrarenal NO synthesis inhibition with NG-nitro-L-arginine methyl ester (L-NAME, 3 micrograms.kg-1.min-1 intrarenally). Under control conditions, the meat meal resulted in significant renal hyperemia. Three hours after ingestion of the meat meal, GFR (43 +/- 3 to 59 +/- 6 ml/min) and RPF (128 +/- 10 to 160 +/- 17 ml/min) progressively increased by approximately 40 and 25%, respectively. In contrast, pretreatment with intrarenal infusion of L-NAME abolished the GFR (48 +/- 6 to 52 +/- 6 ml/min) and RPF (129 +/- 20 to 121 +/- 17 ml/min) increases induced by the meat meal. Pretreatment with L-arginine (0.5 mg.kg-1.min-1) plus L-NAME (3 micrograms.kg-1.min-1) did not modify the meat meal-induced changes in GFR (41 +/- 4 to 66 +/- 6 ml/min) and RPF (127 +/- 9 to 182 +/- 14 ml/min). In summary, a meat meal in dogs results in marked increases in RPF and GFR. Intrarenal NO synthesis inhibition abolished the RPF and GFR responses to the meat meal.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of the SARS-CoV-2 virus in the appearance of new onset type 1 diabetes mellitus in children in Gran Canaria, Spain

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Yeray Nóvoa-Medina ◽  
Svetlana Pavlovic-Nesic ◽  
Jesús Ma González-Martín ◽  
Araceli Hernández-Betancor ◽  
Sara López ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Direct Relationship ◽  
Igg Antibodies ◽  
Past Infection ◽  
Gran Canaria ◽  
Type 1 Dm ◽  
New Onset

Abstract Objectives It has been hypothesized that SARS-CoV-2 may play a role in the development of different forms of diabetes mellitus (DM). The Canary Islands have the highest incidence of type 1 DM (T1DM) reported in Spain (30–35/100,000 children under 14 years/year). In 2020–2021 we observed the highest incidence so far on the island of Gran Canaria, as a result of which we decided to evaluate the possible role of COVID-19 in the increased number of onsets. Methods We examined the presence of IgG antibodies against SARS-CoV-2 in children with new onset T1DM between October 2020 and August 2021. We compared recent T1DM incidence with that of the previous 10 years. Results Forty-two patients were diagnosed with T1DM (48.1/100,000 patients/year), representing a nonsignificant 25.7% increase from the expected incidence. Of the 33 patients who consented to the study, 32 presented negative IgG values, with only one patient reflecting undiagnosed past infection. Forty-four percent of patients presented with ketoacidosis at onset, which was similar to previous years. Conclusions We conclude that there is no direct relationship between the increased incidence of T1DM and SARS-CoV-2 in the region. The COVID-19 pandemic did not result in an increased severity of T1DM presentation.

Monogenic Diabetes: Genetics and Relevance on Diabetes Mellitus Personalized Medicine

2020 ◽  
Vol 16 (8) ◽  
pp. 807-819 ◽  
Author(s):  
Madalena Sousa ◽  
Jácome Bruges-Armas
Keyword(s):  
Diabetes Mellitus ◽  
Complex Disease ◽  
Clinical Manifestations ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Diabetes Genetics ◽  
Individualize Treatment

Background: Diabetes mellitus (DM) is a complex disease with significant impression in today's world. Aside from the most common types recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM), recent studies have emphasized the crucial role of genetics in DM, allowing the distinction of monogenic diabetes. Methods: Authors did a literature search with the purpose of highlighting and clarifying the subtypes of monogenic diabetes, as well as the accredited genetic entities responsible for such phenotypes. Results: The following subtypes were included in this literature review: maturity-onset diabetes of the young (MODY), neonatal diabetes mellitus (NDM) and maternally inherited diabetes and deafness (MIDD). So far, 14 subtypes of MODY have been identified, while three subtypes have been identified in NDM - transient, permanent, and syndromic. Discussion: Despite being estimated to affect approximately 2% of all the T2DM patients in Europe, the exact prevalence of MODY is still unknown, accentuating the need for research focused on biomarkers. Consequently, due to its impact in the course of treatment, follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Conclusion: Currently, advances in the genetics field allowed the recognition of new DM subtypes, which until now, were considered slight variations of the typical forms. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations, to facilitate diagnosis and individualize treatment.

scholarly journals A literature review and meta-analysis of safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junichi Mukai ◽  
Shinya Kanno ◽  
Rie Kubota
Keyword(s):  
Diabetes Mellitus ◽  
Meta Analysis ◽  
Japanese Patients ◽  
Sglt2 Inhibitors ◽  
Patients With Diabetes ◽  
Language Restriction ◽  
Calculated Risk ◽  
Favorable Safety ◽  
Type 1 Dm

AbstractThe safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

2016 ◽  
Vol 174 (4) ◽  
pp. R127-R138 ◽  
Author(s):  
F S Hough ◽  
D D Pierroz ◽  
C Cooper ◽  
S L Ferrari ◽  
_ _
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Bone Fragility ◽  
Mineral Density ◽  
Good Glycaemic Control ◽  
Marrow Adiposity ◽  
Igf1 Deficiency

Subjects with type 1 diabetes mellitus (T1DM) have decreased bone mineral density and an up to sixfold increase in fracture risk. Yet bone fragility is not commonly regarded as another unique complication of diabetes. Both animals with experimentally induced insulin deficiency syndromes and patients with T1DM have impaired osteoblastic bone formation, with or without increased bone resorption. Insulin/IGF1 deficiency appears to be a major pathogenetic mechanism involved, along with glucose toxicity, marrow adiposity, inflammation, adipokine and other metabolic alterations that may all play a role on altering bone turnover. In turn, increasing physical activity in children with diabetes as well as good glycaemic control appears to provide some improvement of bone parameters, although robust clinical studies are still lacking. In this context, the role of osteoporosis drugs remains unknown.

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