scholarly journals Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection

2020 ◽  
Vol 21 (2) ◽  
pp. 645
Author(s):  
Selma B. Souto ◽  
Joana R. Campos ◽  
Joana F. Fangueiro ◽  
Amélia M. Silva ◽  
Nicola Cicero ◽  
...  

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal–regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Lina T. Al Kury

Diabetes mellitus (DM) is a chronic metabolic disorder commonly characterized by high blood glucose levels, resulting from defects in insulin production or insulin resistance, or both. DM is a leading cause of mortality and morbidity worldwide, with diabetic cardiomyopathy as one of its main complications. It is well established that cardiovascular complications are common in both types of diabetes. Electrical and mechanical problems, resulting in cardiac contractile dysfunction, are considered as the major complications present in diabetic hearts. Inevitably, disturbances in the mechanism(s) of Ca2+ signaling in diabetes have implications for cardiac myocyte contraction. Over the last decade, significant progress has been made in outlining the mechanisms responsible for the diminished cardiac contractile function in diabetes using different animal models of type I diabetes mellitus (TIDM) and type II diabetes mellitus (TIIDM). The aim of this review is to evaluate our current understanding of the disturbances of Ca2+ transport and the role of main cardiac proteins involved in Ca2+ homeostasis in the diabetic rat ventricular cardiomyocytes. Exploring the molecular mechanism(s) of altered Ca2+ signaling in diabetes will provide an insight for the identification of novel therapeutic approaches to improve the heart function in diabetic patients.


2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
T. Forst ◽  
T. Kunt ◽  
B. Wilhelm ◽  
M. M. Weber ◽  
A. Pfützner

During the recent years, the role of C-peptide, released from the pancreatic beta cell, in regulating microvascular blood flow, has received increasing attention. In type 1 diabetic patients, intravenous application of C-peptide in physiological concentrations was shown to increase microvascular blood flow, and to improve microvascular endothelial function and the endothelial release of NO. C-peptide was shown to impact microvascular blood flow by several interactive pathways, like stimulatingNa+K+ATPase or the endothelial release of NO. There is increasing evidence, that in patients with declining beta cell function, the lack of C-peptide secretion might play a putative role in the development of microvascular blood flow abnormalities, which go beyond the effects of declining insulin secretion or increased blood glucose levels.


2019 ◽  
Vol 12 (1) ◽  
pp. 1
Author(s):  
Nur Qadri Rasyid ◽  
Muawanah Usman

Diabetes mellitus is a metabolic disorder / disease characterized by high blood glucose levels (hyperglycemia) with changes in carbohydrate, lipid, and protein metabolism in the body due to disruption in insulin action, insulin secretion or both. These metabolic changes affect the concentration of electrolytes. Electrolytes contained in the body play an important role in many body processes, such as controlling fluid levels, acid base balance (pH), nerve conduction, blood clotting and muscle contraction. Sodium, potassium and chloride are the most common macroelectrolytes and correlate with diabetes mellitus. In this study, we examined the prevalence of diabetes and its relationship to electrolyte concentrations in 28 subjects, divided into two groups: group A consisted of 14 diabetic patients in Labuang Baji Hospital and group B consisting of 14 non-diabetic subjects. The results of the research conducted showed that serum electrolyte levels (Na +, K +, Cl-) for the control were all in the normal range. In contrast, serum electrolyte (Na +, Cl-) levels have two patients who have Na + electrolyte levels below the normal range.  


Author(s):  
Ifeoma Priscilla Ezeugwunne ◽  
◽  

Type 2 diabetes mellitus is the most common type of diabetes, having high blood glucose, reduced insulin secretion and / or inadequate glucagon secretion. The study is to assess the activities of pancreatic enzymes and anthropometric indices. 81 participants comprised 38 diabetic and 43 control were randomly recruited. Informed, oral and written consent was obtained from the participants. Ethical approval was obtained.6mls of fasting blood samples were collected. Plasma glucose; amylase and lipase activities were analyzed using standard laboratory methods. Body mass index (BMI) of participant was determined from height and weight. The results showed significantly increased plasma glucose level in the diabetic participants than in control at p=0.000 and in male diabetics than in female diabetics at p=0.048 in each case. But the activities of lipase, amylase, the mean age and BMI level were the same in both diabetic and control groups at p>0.05 respectively. BMI level, lipase and amylase activities were the same in both genders (p>0.05). Stronger positive correlation exist between Weight Vs BMI (r=0.834; p=0.000), followed by Lipase Vs Amylase (r=0.767; p=0.000), least between Age Vs BMI (r=0.353; p=0.022) but weaker negative associations exist between Height Vs BMI (r=-0.490; p=0.001) and Weight Vs FBS (r=-0.325; p=0.036) in the diabetic subjects. The significant higher level of blood glucose; stronger positive correlation between Lipase and Amylase; Weight and BMI may likely revealed pancreatic exocrine function abnormality in diabetes mellitus type 2.


2019 ◽  
Author(s):  
Samuel Dagogo-Jack

The long-term complications of diabetes mellitus include those attributable to hyperglycemia-mediated small vessel (microvascular)and neuropathic complications and syndromes resulting from multifactorial large vessel disease (macrovascular complications). Diabetic patients with evidence of chronic complications are best managed in consultation with appropriate specialists. The microvascular and neuropathic complications, which are specifically related to hyperglycemia, include retinopathy, nephropathy, and diabetic neuropathy. This review contains 8 figures, 9 tables, and 83 references. Key Words: Hyperglycemia, hypoglycemia, macrovascular, microvascular, neuropathic


1997 ◽  
Vol 18 (9) ◽  
pp. 575-577 ◽  
Author(s):  
Richard T. Laughlin ◽  
Fredrick Reeve ◽  
Douglas G. Wright ◽  
Jon T. Mader ◽  
Jason H. Calhoun

Plantar puncture wounds to the foot are a common injury. A small number (1.8%) of these puncture wounds become infected and progress to osteomyelitis. The purpose of this article is to report the cases of six patients who developed osteomyelitis of the calcaneus after a puncture wound to the heel caused by a nail. The characteristics of the patients, the pathogenic organism, and the outcome were studied. Patients who were healthy and had no systemic illness (N = 4) had only one pathogenic organism cultured, whereas patients who had systemic illness (diabetes mellitus, N = 2) had more than one pathogenic organism cultured. The only amputation in this group occurred in a patient with diabetes mellitus. It was concluded that diabetic patients who develop calcaneal osteomyelitis from a nail puncture wound are more likely to have multiple pathogens cultured. Furthermore, if a diabetic neuropathy is also present, the nail puncture wound may be the initial injury leading to a chronic ulceration, increasing the risk of amputation.


2004 ◽  
Vol 5 (1) ◽  
pp. 51-64 ◽  
Author(s):  
T. Forst ◽  
T. Kunt

Beside functional and structural changes in vascular biology, alterations in the rheologic properties of blood cells mainly determines to an impaired microvascular blood flow in patients suffering from diabetes mellitus. Recent investigations provide increasing evidence that impaired C-peptide secretion in type 1 diabetic patients might contribute to the development of microvascular complications. C-peptide has been shown to stimulate endothelial NO secretion by activation of theCa2+calmodolin regulated enzyme eNOS. NO himself has the potency to increase cGMP levels in smooth muscle cells and to activateNa+K+ATPase activity and therefore evolves numerous effects in microvascular regulation. In type 1 diabetic patients, supplementation of C-peptide was shown to improve endothelium dependent vasodilatation in an NO-dependent pathway in different vascular compartments. In addition, it could be shown that C-peptide administration in type 1 diabetic patients, results in a redistribution of skin blood flow by increasing nutritive capillary blood flow in favour to subpapillary blood flow. ImpairedNa+K+ATPase in another feature of diabetes mellitus in many cell types and is believed to be a pivotal regulator of various cell functions. C-peptide supplementation has been shown to restoreNa+K+ATPase activity in different cell types during in vitro and in vivo investigations. In type 1 diabetic patients, C-peptide supplementation was shown to increase erythrocyteNa+K+ATPase activity by about 100%. There was found a linear relationship between plasma C-peptide levels and erythrocyteNa+K+ATPase activity. In small capillaries, microvascular blood flow is increasingly determined by the rheologic properties of erythrocytes. Using laser-diffractoscopie a huge improvement in erythrocyte deformability could be observed after C-peptide administration in erythrocytes of type 1 diabetic patients. Inhibition of theNa+K+ATPase by Obain completely abolished the effect of C-peptide on erythrocyte deformability. In conclusion, C-peptide improves microvascular function and blood flow in type 1 diabetic patients by interfering with vascular and rheological components of microvascular blood flow.


2015 ◽  
Vol 23 (6) ◽  
pp. 707-714 ◽  
Author(s):  
Kazuyoshi Nakanishi ◽  
Nobuhiro Tanaka ◽  
Naosuke Kamei ◽  
Takeshi Hiramatsu ◽  
Satoshi Ujigo ◽  
...  

OBJECT The occurrence of compressive cervical myelopathy (CCM) increases in adults over 50 years of age. In addition, diabetes mellitus (DM) is a frequent comorbidity for people of this age and may impact the severity of CCM. The authors assessed motor pathway function in diabetic patients with CCM to investigate the correlation between electrophysiological parameters and clinical symptoms. METHODS Motor evoked potentials (MEPs) were measured from the abductor digiti minimi muscle (ADM) and the abductor hallucis muscle (AH) following transcranial magnetic stimulation, as were M- and F-waves following electrical stimulation of the ulnar and tibial nerves, in 22 patients with CCM and diabetes mellitus (DM) who had not experienced symptomatic diabetic neuropathy (CCM-DM group), in 92 patients with CCM alone (CCM group), and in 24 healthy adults (control group). The peripheral conduction time (PCT; measured from the ADM and AH) was calculated as follows: (M-wave latency + F-wave latency −1)/2. The central motor conduction time (CMCT; measured from the ADM and AH) was calculated by subtracting the PCT from the onset latency of the MEPs. The Japanese Orthopaedic Association (JOA) score for cervical myelopathy was obtained before and 1 year after surgery as a clinical outcome measure. RESULTS MEP, PCT, and CMCT parameters in the CCM-DM and CCM groups were significantly longer than those in the control group (p = 0.000−0.007). The PCTs in the CCM-DM group were significantly longer than those in the CCM group (p = 0.001−0.003). No significant differences were detected in the MEP and CMCT parameters between the CCM-DM and CCM groups (p = 0.080–1.000). The JOA score before surgery in the CCM-DM group was 10.7 ± 2.0 points and was significantly lower than that in the CCM group (12.2 ± 2.5 points, p = 0.015). In the CCM-DM group, JOA scores before surgery correlated with MEP-AH (r = −0.610, p = 0.012) and PCT-AH (r = −0.676, p = 0.004) values, but not with CMCT values, while the JOA scores were related to both MEP and CMCT parameters in the CCM group. The JOA scores improved to 13.8 ± 2.2 points after surgery (p = 0.001) and correlated with MEP-AH (r = −0.667, p = 0.005) and PCT-AH (r = −0.611, p = 0.012) in the CCM-DM group. CONCLUSIONS The results suggest that MEP, PCT, and CMCT parameters each reveal abnormalities in the upper and lower motor neurons even in patients with DM. The results also show a prolonged PCT in CCM-DM patients, despite having no history of diabetic neuropathy. Corticospinal tract impairments are similar between CCM and CCM-DM patients, while the JOA score of the CCM-DM patients is lower than that in the CCM patients. The JOA score in CCM-DM patients may be influenced by additional impairments in peripheral nerves or other diabetic complications. These electrophysiological studies may be useful for screening motor pathway function for CCM in patients with DM.


2019 ◽  
pp. 8-12
Author(s):  
N.V. Hudiakova ◽  
N.V. Ivanov ◽  
I. Yu. Pchelin ◽  
A.N. Shishkin ◽  
N.V. Vorokhobina ◽  
...  

The present review summarizes the results of global studies and assesses contribution of hyperglycemia towards formation of neurologic complications in diabetic patients. Hyperglycemia is believed to play a leading role in the formation of neurological complications in diabetes mellitus. However, the achievement of normalization of glycemia level does not ensure the cessation of their development and progression, which indicates a lack of knowledge about the pathogenetic relationships in diabetic neuropathy. Limited understanding of these issues entails the absence of treatment options that effectively affect the course of this complication. Based on the analysis of experimental and clinical studies of recent years, data on the molecular-biological relationships of hyperglycemia with the formation of neurological complications in diabetes mellitus are summarized. The influence of the oxidative and nitrosative stress, advanced glycation end products, the activation of the polyol and hexosamine pathways on the state of the nerve fiber is analyzed. The data on molecular mechanisms of development of diabetic neuropathy are contradictory. On the basis of recent experimental and clinical data we review possibilities for pathogenetic therapy. The problem of oppositely directed effects of treatment is discussed. Clinical rationale is given for declared direction of further studies.


2021 ◽  
Vol 17 ◽  
Author(s):  
Moyad Shahwan ◽  
Nageeb Hassan ◽  
Rima Ahd Shaheen ◽  
Ahmed Gaili ◽  
Ammar Jairoun ◽  
...  

Abstract:: Diabetes mellitus (DM) which is defined as high blood glucose level is a major public health worldwide. While discussing DM, the knowledge in this field is unlimited hence a syndrome that populations are living with for more than a decade is always an important matter to keep searching for updates on it. Challenges are always present in different means as comorbidities, poorly controlled DM especially type 2 Diabetes mellitus(T2DM) is considered as a risk factor for a lot of different diseases including but not limited to chronic kidney Disease (CKD). Complications might appear through time, as the aging process changes the body functions, while a significant number of antidiabetic medications are cleared eventually by the kidney; this increase the burden on kidney function placing the diabetic patients at risk. The significant high number of patients with uncontrolled diabetes resulting with kidney disease mirror the importance of this condition on patient’s quality of life. This review presents an overview, pathophysiology, etiology and prevalence of Chronic Kidney Disease (CKD) and abnormal renal parameters correlated with poorly controlled T2DM, with emphasis on and clinical studies involving the association between vitamin D Insufficiency/Deficiency and chronic kidney disease among patients with T2DM.


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