- TINU-associated Fanconi syndrome: a case report and review of literature. [Journal Article]
- BNBMC Nephrol 2018 Oct 19; 19(1):274
- CONCLUSIONS: We reviewed the literature and found nine similar cases. This association mostly occurs in adult woman, without current evidence for an ethnic predilection, unlike previously reported. The renal prognosis seems favorable after corticosteroid therapy, even in case of severe renal injury. Nonetheless mild tubular defects may persist after treatment or spontaneous remission.
- Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. [Journal Article]
- OSObes Sci Pract 2018; 4(5):477-482
- CONCLUSIONS: Canagliflozin significantly reduced the serum levels of BS, HbA1C, TG, UA and ferritin, as well as FIB-4 index values and body weight, with improved liver function. Sodium glucose cotransporter 2 inhibitors may be an important therapeutic modality for improving liver injury in NAFLD patients.
- Isolation and Characterization of Pancreatic Canine Fetal Cells at the Final Stage of Gestation. [Journal Article]
- ARAnat Rec (Hoboken) 2018 Oct 17
- The incidence of diabetes mellitus in dogs is increasing in recent years, mainly because of genetic and/or environmental factors, including endocrine disorders (like in humans); failure of suitable c...
The incidence of diabetes mellitus in dogs is increasing in recent years, mainly because of genetic and/or environmental factors, including endocrine disorders (like in humans); failure of suitable control of blood sugar levels, which triggers hyperglycemia; glycosuria and weight loss, which demands the development of innovative treatments to cure or treat this complex disease in dogs. The present study established for the first time a protocol to obtain and characterize cells derived from pancreas of canine fetuses. Those fetuses do not have a defined breed and were at the final stage of gestation. The protocol aims to provide morphological data to enable future applications of these cells for therapeutic approaches. In cell culture, pancreatic cells showed a fibroblast-like appearance with a mono-layered growth pattern and were not tumorigenic. They exhibited a positive expression for the pluripotent proliferation markers NANOG and PCNA and expressed PDX1, a transcription factor that is important for activation of the insulin gene promoter. In addition, Tyrosine Hydroxylase-positive (TH+) sympathetic nerve fibers were identified. Histologically, the pancreatic epithelium was developed, pancreatic glands in the fetuses were like those in the parenchyma of post-conception dogs and pancreatic islets were unevenly distributed and organized in small clusters along the glands close to the vasculature. Staining with dithizone indicated the presence of insulin in the cells. A large number of beta cells were confirmed by immunofluorescence. In conclusion, the canine fetal pancreas cells could be an alternative and adequate source of cell lineages for stem cell therapies for diabetes treatment. This article is protected by copyright. All rights reserved.
- Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy. [Journal Article]
- IJInt J Mol Sci 2018 Oct 11; 19(10)
- Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or ...
Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney. In contrast, the inhibitor of NFκβ (Iκβ) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms.
- Normal pregnancy induced glucose metabolic stress in a longitudinal cohort of healthy women: Novel insights generated from a urine metabolomics study. [Journal Article]
- MMedicine (Baltimore) 2018; 97(40):e12417
- During normal pregnancy, mothers face a unique physiological challenge in the adaptation of glucose metabolism in preparation for the metabolic stress presented by fetal development. However, the res...
During normal pregnancy, mothers face a unique physiological challenge in the adaptation of glucose metabolism in preparation for the metabolic stress presented by fetal development. However, the responsible mechanism remains elusive. The purpose of this study is to investigate the mechanism of the metabolic stress of glucose metabolism in pregnant women using metabolomics method.A Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometer-based untargeted metabolomics study was performed to investigate the dynamic urinary signature of the intermediates of glucose metabolism in a longitudinal cohort of 232 healthy pregnant women in their first, second, and third trimesters.Twelve glucose metabolic intermediates were screened out from hundreds of candidate metabolites using partial least squares discriminant analysis models. These 12 markers were mainly involved in the metabolic pathways of insulin resistance, glycolysis/gluconeogenesis, tricarboxylic acid cycle, nonabsorbable carbohydrate metabolism, and N-glycan biosynthesis. In particular, L-acetylcarnitine, a metabolite that is beneficial for the amelioration of insulin resistance, decreased in a time-dependent manner during normal pregnancy. Moreover, thiamine pyrophosphate, an intermediate product of glycolysis/gluconeogenesis, significantly increased in the second trimester, and argininosuccinic acid and oxalosuccinic acid, intermediates involved in the tricarboxylic acid cycle, significantly decreased in the third trimester, suggesting an increased glucose demand in the maternal body during fetal development.These findings provide novel insight into the normal pregnancy-induced elevation of insulin resistance and glycolysis/gluconeogenesis, as well as the observed reduction in the aerobic oxidation of glucose.
- Diabetes Modulates MicroRNAs 29b-3p, 29c-3p, 199a-5p and 532-3p Expression in Muscle: Possible Role in GLUT4 and HK2 Repression. [Journal Article]
- FEFront Endocrinol (Lausanne) 2018; 9:536
- The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (...
The reduced expression of solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) and hexokinase-2 (HK2) in skeletal muscle participates in insulin resistance of diabetes mellitus (DM). MicroRNAs (miRNAs) have emerged as important modulators of mRNA/protein expression, but their role in DM is unclear. We investigated miRNAs hypothetically involved in GLUT4/HK2 expression in soleus muscle of type 1 diabetes-like rats. In silico analysis revealed 651 miRNAs predicted to regulate solute carrier family 2 member 4 (Slc2a4) mRNA, several of them also predicted to regulate Hk2 mRNA, and 16 miRNAs were selected for quantification. Diabetes reduced Slc2a4/GLUT4 and Hk2/HK2 expression (50-77%), upregulated miR-29b-3p and miR-29c-3p (50-100%), and downregulated miR-93-5p, miR-150-5p, miR-199a-5p, miR-345-3p, and miR-532-3p (~30%) expression. Besides, GLUT4 and HK2 proteins correlated (P < 0.05) negatively with miR-29b-3p and miR-29c-3p and positively with miR-199a-5p and miR-532-3p, suggesting that these miRNAs could be markers of alterations in GLUT4 and HK2 expression. Additionally, diabetes increased the nuclear factor kappa B subunit 1 protein (p50) expression, a repressor of Slc2a4, which was also predicted as a target for miR-199a-5p and miR-532-3p. Correlations were also detected between these miRNAs and blood glucose, 24-h glycosuria and plasma fructosamine, and insulin therapy reversed most of the alterations. In sum, we report that diabetes altered miR-29b-3p, miR-29c-3p, miR-199a-5p and miR-532-3p expression in muscle of male rats, where their predicted targets Slc2a4/GLUT4 and Hk2/HK2 are repressed. These data shed light on these miRNAs as a markers of impaired skeletal muscle glucose disposal, and, consequently, glycemic control in diabetes.
- Use of dapagliflozin in patients with advanced diabetic kidney disease. [Journal Article]
- KRKidney Res Clin Pract 2018; 37(3):292-297
- Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective for overweight diabetic patients through the induction of glucosuria. However, SGLT2 inhibitors are not recommended for patients with a...
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are effective for overweight diabetic patients through the induction of glucosuria. However, SGLT2 inhibitors are not recommended for patients with advanced chronic kidney disease (CKD) because they may aggravate renal function and thus become less effective in controlling blood glucose in this patient population. We suggest that adequate hydration would be helpful to prevent the side effects of SGLT2 inhibitors in diabetic patients with advanced CKD. In this study, we review five cases of SGLT2 inhibitor therapy, specifically with dapagliflozin, for the treatment of diabetes mellitus in patients with advanced CKD. The patients experienced dramatic weight reduction, improved glucose control, and further benefits without aggravation of renal function.
- Tenofovir-induced renal tubular dysfunction among human immunodeficiency virus patients on antiretroviral therapy in Nigeria: Prospects for early detection of presymptomatic nephrotoxicity. [Journal Article]
- KRKidney Res Clin Pract 2018; 37(3):230-238
- CONCLUSIONS: Indicators of tubular dysfunction were markedly higher among patients on the TDF-based treatment regimen. Biomarkers of tubular dysfunction could be useful for detecting pre-symptomatic nephrotoxicity before marked reduction of glomerular filtration rate in HIV patients on TDF.
- SGLT1 inhibition: Pros and cons. [Review]
- EJEur J Pharmacol 2018 Nov 05; 838:153-156
- Sodium Glucose Cotransporters 1 (SGLT1) play important roles in the intestinal absorption of glucose and the renal reabsorption of glucose, especially in patients with uncontrolled diabetes and those...
Sodium Glucose Cotransporters 1 (SGLT1) play important roles in the intestinal absorption of glucose and the renal reabsorption of glucose, especially in patients with uncontrolled diabetes and those receiving SGLT2 inhibitors. As a consequence, the inhibition of SGLT1 transporters may represent an interesting therapeutic option in patients with diabetes. However, genetic models of SGLT1 inactivation indicate that the malfunction of these transporters may have adverse effects on various tissues. In this review, we discuss the available evidence on the beneficial and detrimental effects that the inhibition of SGLT1 transporters might have. The inhibition of SGLT1 lowers serum glucose levels through the inhibition of intestinal absorption and renal reabsorption of glucose. In addition, drugs that interfere with SGLT1-mediated transport of glucose may protect cardiac tissue by reducing glycogen accumulation and decreasing the production of reactive oxygen species. On the other hand, this strategy may result in diarrhea, volume depletion, may interfere with the correction of hypoglycemia through the oral administration of carbohydrates and could predispose to the development of euglycemic diabetic ketoacidosis. Therefore, at the moment, SGLT1 inhibition seems to represent a two-edged sword.
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- Metabolic Acidosis in Postsurgical Patient on Canagliflozin and Metformin: A Case Report. [Journal Article]
- PA A Pract 2018 Sep 18
- Canagliflozin is a novel drug for diabetes mellitus with the mechanisms of inducing glucosuria through inhibition of the sodium-glucose cotransporter 2 in the kidney independent of insulin activity. ...
Canagliflozin is a novel drug for diabetes mellitus with the mechanisms of inducing glucosuria through inhibition of the sodium-glucose cotransporter 2 in the kidney independent of insulin activity. We are reporting euglycemic ketoacidosis with severe life-threatening metabolic acidosis. The 2 patients described had type 2 diabetes mellitus and were in a state of relative starvation after abdominal surgery. The first patient had been given an oral diet but was restricted with regard to calorie and sugar intake. The second patient had been nil per os since the operation.