scholarly journals C-peptide corrects endoneurial blood flow but not oxidative stress in type 1 BB/Wor rats

2004 ◽  
Vol 287 (3) ◽  
pp. E497-E505 ◽  
Author(s):  
Martin J. Stevens ◽  
Weixian Zhang ◽  
Fei Li ◽  
Anders A. F. Sima

Oxidative stress and neurovascular dysfunction have emerged as contributing factors to the development of experimental diabetic neuropathy (EDN) in streptozotocin-diabetic rodents. Additionally, depletion of C-peptide has been implicated in the pathogenesis of EDN, but the mechanisms of these effects have not been fully characterized. The aims of this study were therefore to explore the effects of diabetes on neurovascular dysfunction and indexes of nerve oxidative stress in type 1 bio-breeding Worcester (BB/Wor) rats and type 2 BB Zucker-derived (ZDR)/Wor rats and to determine the effects of C-peptide replacement in the former. Motor and sensory nerve conduction velocities (NCVs), hindlimb thermal thresholds, endoneurial blood flow, and indicators of oxidative stress were evaluated in nondiabetic control rats, BB/Wor rats, BB/Wor rats with rat II C-peptide replacement (75 nmol C-peptide·kg body wt−1·day−1) for 2 mo, and diabetes duration-matched BBZDR/Wor rats. Endoneurial perfusion was decreased and oxidative stress increased in type 1 BB/Wor rats. C-peptide prevented NCV and neurovascular deficits and attenuated thermal hyperalgesia. Inhibition of nitric oxide (NO) synthase, but not cyclooxygenase, reversed the C-peptide-mediated effects on NCV and nerve blood flow. Indexes of oxidative stress were unaffected by C-peptide. In type 2 BBZDR/Wor rats, neurovascular deficits and increased oxidative stress were unaccompanied by sensory NCV slowing or hyperalgesia. Therefore, nerve oxidative stress is increased and endoneurial perfusion decreased in type 1 BB/Wor and type 2 BBZDR/Wor rats. NO and neurovascular mechanisms, but not oxidative stress, appear to contribute to the effects of C-peptide in type 1 EDN. Sensory nerve deficits are not an inevitable consequence of increased oxidative stress and decreased nerve perfusion in a type 2 diabetic rodent model.

Diabetes Care ◽  
2006 ◽  
Vol 30 (1) ◽  
pp. 71-76 ◽  
Author(s):  
K. Ekberg ◽  
T. Brismar ◽  
B.-L. Johansson ◽  
P. Lindstrom ◽  
L. Juntti-Berggren ◽  
...  

2021 ◽  
Author(s):  
Arshpal Gill ◽  
Ra’ed Nassar ◽  
Ruby Sangha ◽  
Mohammed Abureesh ◽  
Dhineshreddy Gurala ◽  
...  

Hepatorenal Syndrome (HRS) is an important condition for clinicians to be aware of in the presence of cirrhosis. In simple terms, HRS is defined as a relative rise in creatinine and relative drop in serum glomerular filtration rate (GFR) alongside renal plasma flow (RPF) in the absence of other competing etiologies of acute kidney injury (AKI) in patients with hepatic cirrhosis. It represents the end stage complication of decompensated cirrhosis in the presence of severe portal hypertension, in the absence of prerenal azotemia, acute tubular necrosis or others. It is a diagnosis of exclusion. The recognition of HRS is of paramount importance for clinicians as it carries a high mortality rate and is an indication for transplantation. Recent advances in understanding the pathophysiology of the disease improved treatment approaches, but the overall prognosis remains poor, with Type I HRS having an average survival under 2 weeks. Generally speaking, AKI and renal failure in cirrhotic patients carry a very high mortality rate, with up to 60% mortality rate for patients with renal failure and cirrhosis and 86.6% of overall mortality rates of patients admitted to the intensive care unit. Of the various etiologies of renal failure in cirrhosis, HRS carries a poor prognosis among cirrhotic patients with acute kidney injury. HRS continues to pose a diagnostic challenge. AKI can be either pre-renal, intrarenal or postrenal. Prerenal causes include hypovolemia, infection, use of vasodilators and functional due to decreased blood flow to the kidney, intra-renal such as glomerulopathy, acute tubular necrosis and post-renal such as obstruction. Patients with cirrhosis are susceptible to developing renal impairment. HRS may be classified as Type 1 or rapidly progressive disease, and Type 2 or slowly progressive disease. There are other types of HRS, but this chapter will focus on Type 1 HRS and Type 2 HRS. HRS is considered a functional etiology of acute kidney injury as there is an apparent lack of nephrological parenchymal damage. It is one several possibilities for acute kidney injury in patients with both acute and chronic liver disease. Acute kidney injury (AKI) is one of the most severe complications that could occur with cirrhosis. Up to 50% of hospitalized patients with cirrhosis can suffer from acute kidney injury, and as mentioned earlier an AKI in the presence of cirrhosis in a hospitalized patient has been associated with nearly a 3.5-fold increase in mortality. The definition of HRS will be discussed in this chapter, but it is characterized specifically as a form of acute kidney injury that occurs in patients with advanced liver cirrhosis which results in a reduction in renal blood flow, unresponsive to fluids this occurs in the setting of portal hypertension and splanchnic vasodilation. This chapter will discuss the incidence of HRS, recognizing HRS, focusing mainly on HRS Type I and Type II, recognizing competing etiologies of renal impairment in cirrhotic patients, and the management HRS.


2005 ◽  
Vol 11 (3) ◽  
pp. 177-180 ◽  
Author(s):  
L. A. Lohankova ◽  
Yu. V. Kotovskaya ◽  
A. S. Milto ◽  
Zh. D. Kobalava

The structural and functional features of the microcirculatory heel (MCB) were studied in patients with arterial hypertension (AH) in relation to the presence or absence of type 1 diabetes mellitus (DM). Two hundred and twelve patients were examined. These included 110 patients with grades 1 and 2 arterial hypertension (AH) and type 2 DM, 82 patients with AH without type 2 DM, and 20 apparently healthy individuals. Laser Doppler flowmetry (LDF) was used to estimate basal blood flow, the loading test parameters characterizing the structural and functional status of MCB, and the incidence of hemodynamic types of microcirculation. Patients with AH concurrent with type 1 DM were found to have the following microcirculatory features: an increase in perfusion blood flow (microcirculation index, 8,8±1,8 perf. units versus 4,9±0,8 perf, units in patients with AH without DM and 6,7±0,9 perf. units in the control group), a drastic reduction in myogenic activity to 13,2±5,7 % versus 16,7±6,8 and 25,2±6,4 %, respectively, a decrease in vascular resistance, impairment of autoregulation, and low reserve capacities (reserve capillary blood flow was 197,8±31,6 % versus 429,9±82,01 % in the group of AH without DM and 302,8±50,1 % in the control group), a predominance of the hyperemic hemodynamic type (58,8 % in patients with AH and DM, 20,9 % in those with AH without DM, and 20,0 % in the controls). The specific features of the altered microcirculatory bed in patients with AH concurrent with type 2 DM were ascertained. These included the predominance of hyperemic microcirculation, impaired autoregulation. diminished microvascular resistance, and the low reserve capacities of the microcirculatory bed.


2007 ◽  
Vol 48 (6) ◽  
pp. 628-634 ◽  
Author(s):  
M. Loy ◽  
E. Perra ◽  
A. Melis ◽  
M. E. Cianchetti ◽  
M. Piga ◽  
...  

Background: Amiodarone-induced thyrotoxicosis (AIT) may be caused by excessive thyroidal hormone synthesis and release (type 1) or by a destructive process (type 2). This differentiation is considered essential for therapeutic choice. Purpose: To evaluate the utility of color-flow Doppler sonography (CFDS) in the differential diagnosis and management of AIT. Material and Methods: The clinical and laboratory data, thyroid sonography (grayscale sonography [GSS], CFDS), thyroid radioiodine uptake (RAIU) and thyroid scintigraphy, treatment, and clinical outcome were retrospectively reviewed in 21 AIT patients. The CFDS pattern of thyroid nodules was separately described from that of the perinodular parenchyma, and AIT was classified as type 1 (increased blood flow) or type 2 (low/no blood flow). Type 1 AIT patients were treated with methimazole (alone or associated with potassium perchlorate), while type 2 patients were treated with prednisone or amiodarone withdrawal alone. Results: Eleven patients with increased blood flow were considered as type 1, and 10 with low/no blood flow as type 2. Ten of the 11 patients in the first group showed a hypervascular nodular pattern, while one showed a hypervascular parenchymal pattern. Clinical diagnoses were toxic nodular goiter and Graves' disease, respectively. Of the 10 patients with low/no blood flow, six had normal thyroid volume, three small diffuse goiter, and one small multinodular goiter. The clinical outcome showed that 20 of the 21 patients were treatment responsive. Conclusion: CFDS is a useful tool in the differential diagnosis of AIT. This differentiation appeared to be of clinical relevance as regards therapeutic choice. Separate evaluation of parenchymal blood flow from that of nodules may prove beneficial in the diagnosis of underlying thyroid diseases in patients with type 1 AIT.


2019 ◽  
Vol 20 (21) ◽  
pp. 5423 ◽  
Author(s):  
Mirza Muhammad Fahd Qadir ◽  
Dagmar Klein ◽  
Silvia Álvarez-Cubela ◽  
Juan Domínguez-Bendala ◽  
Ricardo Luis Pastori

Cellular stress, combined with dysfunctional, inadequate mitochondrial phosphorylation, produces an excessive amount of reactive oxygen species (ROS) and an increased level of ROS in cells, which leads to oxidation and subsequent cellular damage. Because of its cell damaging action, an association between anomalous ROS production and disease such as Type 1 (T1D) and Type 2 (T2D) diabetes, as well as their complications, has been well established. However, there is a lack of understanding about genome-driven responses to ROS-mediated cellular stress. Over the last decade, multiple studies have suggested a link between oxidative stress and microRNAs (miRNAs). The miRNAs are small non-coding RNAs that mostly suppress expression of the target gene by interaction with its 3’untranslated region (3′UTR). In this paper, we review the recent progress in the field, focusing on the association between miRNAs and oxidative stress during the progression of diabetes.


2020 ◽  
Vol 179 (7) ◽  
pp. 1115-1120
Author(s):  
Wafaa Elzahar ◽  
Ahmed Arafa ◽  
Amira Youssef ◽  
Adel Erfan ◽  
Doaa El Amrousy

Diabetes ◽  
2002 ◽  
Vol 51 (10) ◽  
pp. 3077-3082 ◽  
Author(s):  
A. Hansen ◽  
B.-L. Johansson ◽  
J. Wahren ◽  
H. von Bibra

Diabetes Care ◽  
2006 ◽  
Vol 29 (9) ◽  
pp. 2034-2038 ◽  
Author(s):  
E. Polska ◽  
J. Kolodjaschna ◽  
F. Berisha ◽  
M. M. Malec ◽  
C. Simader ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3690-3690
Author(s):  
Antonio A. Carrasco-Yalán ◽  
Roberto Fernandez-Vina ◽  
Jorge Castillo-Aguirre ◽  
Hugo Rios ◽  
L. More ◽  
...  

Abstract Background: Recent reports have shown that bone marrow-derived stem cell may contribute to islet regeneration. The goal of our study was to evaluate the safety and efficacy of ABMMC transplantation for patients with IDM. Methods: From June 2005 to January 2007, 28 consecutive patients: 8 Type 1 IDM (T1DM) and 20 Type 2 IDM (T2IDM); who were receiving maximal medical therapy including insulin treatment for 5 years before enrollment. Median time of disease for T2IDM patients was 13 years, without pancreatic islet auto-antibodies. After IRB approval and signed informed consent, bone marrow was harvested and ABMMC were isolated and infused directly into the pancreas via splenic artery using endovascular catheters. Glucose, glycosylated HbA1c and C peptide were measure before and after transplantation. HOMA2 Calculator v2.2 was used to calculated IR and % B (*if Glucose: 3.0 to 25.0 mmol/L and C peptide: 0.2 to 3.5 nmol/L). Results: There were no study related complications. At 1 year follow-up, mean daily insulin requirement was the same in group T1DM and significantly reduced in group T2IDM, from 42.5 to 4.5 U/d (t=7.94, p<0.001). Ten of the twenty (50%) T2IDM established complete insulin independence. Data in table 1. Table 1: Median values PRE POST t p T2IDM (n=20) Fasting Glucose (mmol/L) 10.8 6.6 3.98 0.01 Glycosylated HbA1c (%) 9.6 8.1 3.98 0.01 C peptide (nmol/L) 0.5 0.84 5.11 < 0.01 HOMA 2 IR (n=17)* 2.2 2.26 0.94 0.92 HOMA 2 %B (n=17)* 42.4 130.2 4.9 < 0.01 T1DM (n=8) Fasting Glucose (mmol/L) 10.1 11.1 1.382 0.21 Glycosylated HbA1c (%) 8.7 8.7 0.45 0.66 C peptide (nmol/L) 0.17 0.16 1.00 0.35 Conclusions: The use of ABMMC transplantation for T1DM and T2IDM is safe. In this pilot study, only T2IDM patients have significant improvement in pancreatic function demostrated by better glycemic and HbA1c control, and are associated with a significant independence of the insulin. This has formed for a randomized multi-center study which is currently in progress.


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