C‐peptide prevents NF‐κB from recruiting p300 and binding to the inos promoter in diabetic nephropathy

2018 ◽  
Vol 32 (4) ◽  
pp. 2269-2279 ◽  
Author(s):  
Yanning Li ◽  
Xiaoping Li ◽  
Kunyu He ◽  
Bin Li ◽  
Kun Liu ◽  
...  
2018 ◽  
Vol 43 (6) ◽  
pp. 617-624 ◽  
Author(s):  
Eman A. Elbassuoni ◽  
Neven M. Aziz ◽  
Nashwa F. El-Tahawy

Diabetic nephropathy one of the major microvascular diabetic complications. Besides hyperglycemia, other factors contribute to the development of diabetic complications as the proinsulin connecting peptide, C-peptide. We described the role of C-peptide replacement therapy on experimentally induced diabetic nephropathy, and its potential mechanisms of action by studying the role of nitric oxide (NO) as a mediator of C-peptide effects by in vivo modulating its production by NG-nitro-l-arginine methyl ester (L-NAME). Renal injury markers measured were serum urea, creatinine, tumor necrosis factor alpha, and angiotensin II, and malondialdehyde, total antioxidant, Bcl-2, and NO in renal tissue. In conclusion, diabetic induction resulted in islet degenerations and decreased insulin secretion with its metabolic consequences and subsequent renal complications. C-Peptide deficiencies in diabetes might have contributed to the metabolic and renal error, since C-peptide treatment to the diabetic rats completely corrected these errors. The beneficial effects of C-peptide are partially antagonized by L-NAME coadministration, indicating that NO partially mediates C-peptide effects.


2020 ◽  
Vol 35 (2) ◽  
pp. 158-162
Author(s):  
Yotsapon Thewjitcharoen ◽  
◽  
Sirinate Krittiyawong ◽  
Somboon Vongterapak ◽  
Soontaree Nakasatien ◽  
...  

Objectives. To describe the characteristics of long-standing T1DM in Thai patients and assess residual beta-cell function with status of pancreatic autoantibodies. Methodology. This is a cross-sectional study of Thai subjects with T1DM and disease duration ≥25 years seen at the Theptarin Hospital. Random plasma C-peptide and pancreatic auto-antibodies (Anti-GAD, Anti-IA2, and Anti-ZnT8) were measured. Patients who developed complications were compared with those who remained free of complications. Results. A total of 20 patients (males 65%, mean age 49.4±12.0 years, BMI 22.5±3.1 kg/m2, A1C 7.9±1.6%) with diabetes duration of 31.9±5.1 years were studied. Half of the participants remained free from any diabetic complications while the proportions reporting retinopathy, nephropathy, and neuropathy were 40%, 30%, and 15%, respectively. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy but not in those who were free from other complications. The prevalence rates of anti-GAD, anti-IA2, and anti-ZnT8 were 65%, 20%, and 10%, respectively. None of the patients who tested negative for both anti-GAD and anti-IA2 was positive for anti-ZnT8. Residual beta-cell function based on detectable random plasma C-peptide (≥0.1 ng/mL) and MMTT was found in only 3 patients (15%). There was no relationship between residual beta-cell function and protective effects of diabetic complications. Conclusion. Endogenous insulin secretion persists in some patients with long-standing T1DM and half of longstanding T1DM in Thai patients showed no diabetic complications. HDL cholesterol was significantly higher and triglyceride concentration significantly lower in patients who were free from diabetic nephropathy.


2020 ◽  
Author(s):  
Lúcia Fadiga ◽  
Joana Saraiva ◽  
Diana Catarino ◽  
João Frade ◽  
Miguel Melo ◽  
...  

Abstract Introduction: Adult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA.Methods: We collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed. Results: We included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR – 15) for T1DM and 42 years (IQR – 15) for LADA (p=0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p<0.001). The mean BMI at diagnosis was 24.1Kg/m2 in T1DM group and 26.1Kg/m2 in LADA group (p=0.042). In T1DM group, 67.4% of the patients had more than one positive autoantibody, comparing to 41.3% of LADA patients (p=0.012). There was no statistical difference in what concerns to title of GAD autoantibodies, A1C and C-peptide at diagnosis of autoimmune aetiology. The presence of symptoms at diagnosis was associated with T1DM group (p<0.001). The median daily insulin dose was 40IU for T1DM (0.58IU/Kg) and 33.5IU for LADA (0.57IU/Kg), with no statistical difference. LADA patients were more often under non-insulin antidiabetic drugs (p=0.001). At 10 years follow up, 21.1% of T1DM patients and 63.3% of LADA patients had microvascular complications (p=0.004). Diabetic nephropathy was present in 23.5% of T1DM patients and 53.3% of LADA patients (p=0.047). At the last evaluation, 55.6% of T1DM and 82.6% of LADA patients had metabolic syndrome and this difference was independent of diabetes duration. Conclusion: Patients with classic T1DM presented more often with symptoms, lower BMI and higher number of autoantibodies, which may be related to a more aggressive autoimmune process. Patients with LADA developed more frequently microvascular complications for the same disease duration, namely diabetic nephropathy, and had more often metabolic syndrome.


2010 ◽  
Vol 31 (5) ◽  
pp. 389-397 ◽  
Author(s):  
Claire E. Hills ◽  
Nigel J. Brunskill ◽  
Paul E. Squires

2009 ◽  
Vol 6 (3) ◽  
pp. 203-210 ◽  
Author(s):  
Lina Nordquist ◽  
John Wahren

2020 ◽  
Author(s):  
Lúcia Fadiga ◽  
Joana Saraiva ◽  
Diana Catarino ◽  
João Frade ◽  
Miguel Melo ◽  
...  

Abstract Introduction: Adult-onset autoimmune diabetes (AID) has two different phenotypes: classic type 1 diabetes mellitus (T1DM), with insulin requirement just after diagnosis, and latent autoimmune diabetes in adults (LADA). The purpose of this study is to characterize patients with AID followed on a tertiary centre, comparing classic T1DM and LADA.Methods: We collected data from patients with diabetes and positive islet autoantibodies, aged 30 years old and over at diagnosis. Patients who started insulin in the first 6 months were classified as T1DM and patients with no insulin requirements in the first 6 months were classified as LADA. Data regarding clinical presentation, autoantibodies, A1C and C-peptide at diagnosis, pharmacologic treatment and complications were analysed. Results: We included 92 patients, 46 with classic T1DM and 46 with LADA. The percentage of females was 50% in T1DM group and 52.1% in LADA group. The median age at diagnosis was 38 years (IQR – 15) for T1DM and 42 years (IQR – 15) for LADA (p=0.057). The median time between diagnosis of diabetes and diagnosis of autoimmune aetiology was 0 months in T1DM group and 60 months in LADA group (p<0.001). The mean BMI at diagnosis was 24.1Kg/m2 in T1DM group and 26.1Kg/m2 in LADA group (p=0.042). In T1DM group, 67.4% of the patients had more than one positive autoantibody, comparing to 41.3% of LADA patients (p=0.012). There was no statistical difference in what concerns to title of GAD autoantibodies, A1C and C-peptide at diagnosis of autoimmune aetiology. The presence of symptoms at diagnosis was associated with T1DM group (p<0.001). The median daily insulin dose was 40IU for T1DM (0.58IU/Kg) and 33.5IU for LADA (0.57IU/Kg), with no statistical difference. LADA patients were more often under non-insulin antidiabetic drugs (p=0.001). At 10 years follow up, 21.1% of T1DM patients and 63.3% of LADA patients had microvascular complications (p=0.004). Diabetic nephropathy was present in 23.5% of T1DM patients and 53.3% of LADA patients (p=0.047). At the last evaluation, 55.6% of T1DM and 82.6% of LADA patients had metabolic syndrome (p=0.005). Conclusion: Patients with classic T1DM presented more often with symptoms, lower BMI and higher number of autoantibodies, which may be related to a more aggressive autoimmune process. Patients with LADA developed more frequently microvascular complications for the same disease duration, namely diabetic nephropathy, and had more often metabolic syndrome.


2001 ◽  
Vol 1 (3) ◽  
pp. 261-266 ◽  
Author(s):  
John Wahren ◽  
Karin Ekberg ◽  
Björn Samnegård ◽  
Bo-Lennart Johansson

Life Sciences ◽  
2019 ◽  
Vol 237 ◽  
pp. 116950 ◽  
Author(s):  
Habib Yaribeygi ◽  
Mina Maleki ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar

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