Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas

Emerald, Bright Starling; Mohsin, Sahar; D’Souza, Crystal; John, Annie; Elhasasna, Hussain; Ojha, Shreesh; Raza, Haider; al-Ramadi, Basel K.; Adeghate, Ernest

doi:10.3390/ijms23094974

Cited by 5 publications

(3 citation statements)

References 69 publications

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“…Asparaginase is also not expressed in the pancreas (https://www.proteinatlas.org/ENSG00000166183-ASPG). Several arginine metabolism pathways are not functional in healthy pancreas (e.g., enzymes arginine decarboxylase, arginase, and NO synthase), except for creatine synthesis pathway with proven expression of arginine:glycine amidinotransferase and guanidinoacetate N-methyltransferase (Emerald et al 2022;da Silva et al 2014). However, this pathway does not directly lead to mitochondrial oxidation.…”

Section: Discussionmentioning

confidence: 99%

Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini

Zub,

Manko,

Manko

2024

Pancreas

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Objectives Amino acids play an essential role in protein synthesis, metabolism and survival of pancreatic acini. Adequate nutritional support is important for acute pancreatitis treatment. However, high concentrations of arginine and lysine may induce acute pancreatitis. The study aimed to identify the most suitable L-amino acids as safe energy sources for pancreatic acinar cells. Methods Pancreatic acini were isolated from male Wistar rats. Effects of amino acids (0.1-20 mM) on uncoupled respiration of isolated acini were studied with a Clark electrode. Cell death was evaluated with fluorescent microscopy and DNA gel electrophoresis. Results Among the tested amino acids, glutamate, glutamine, alanine, lysine and aspartate were able to stimulate the uncoupled respiration rate of isolated pancreatic acini, while arginine, histidine and asparagine were not. Lysine, arginine and glutamine (20 mM) caused complete loss of plasma membrane integrity of acinar cells after 24 h of incubation. Glutamine also caused early (2–4 h) cell swelling and blebbing. Aspartate, asparagine and glutamate only moderately decreased the number of viable cells, while alanine and histidine were not toxic. DNA fragmentation assay and microscopic analysis of nuclei showed no evidence of apoptosis in cells treated with amino acids. Conclusions Alanine and glutamate are safe and effective energy sources for mitochondria of pancreatic acinar cells.

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Section: Discussionmentioning

confidence: 99%

Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini

Zub,

Manko,

Manko

2024

Pancreas

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“…Other pathological conditions included an increased severity of obesity-related impaired glucose homeostasis, lipid metabolism disorder and reduced endothelial nitric oxide synthase phosphorylation, as reported in earlier studies. Nitric oxide synthase is an important molecule regulating endothelial function including blood flow and vascular integrity [ 114 , 115 ].…”

Section: Characteristics Of Adropin Knockout Micementioning

confidence: 99%

Adropin’s Role in Energy Homeostasis and Metabolic Disorders

Ali

D’Souza

Singh

et al. 2022

IJMS

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Adropin is a novel 76-amino acid-peptide that is expressed in different tissues and cells including the liver, pancreas, heart and vascular tissues, kidney, milk, serum, plasma and many parts of the brain. Adropin, encoded by the Enho gene, plays a crucial role in energy homeostasis. The literature review indicates that adropin alleviates the degree of insulin resistance by reducing endogenous hepatic glucose production. Adropin improves glucose metabolism by enhancing glucose utilization in mice, including the sensitization of insulin signaling pathways such as Akt phosphorylation and the activation of the glucose transporter 4 receptor. Several studies have also demonstrated that adropin improves cardiac function, cardiac efficiency and coronary blood flow in mice. Adropin can also reduce the levels of serum triglycerides, total cholesterol and low-density lipoprotein cholesterol. In contrast, it increases the level of high-density lipoprotein cholesterol, often referred to as the beneficial cholesterol. Adropin inhibits inflammation by reducing the tissue level of pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin-6. The protective effect of adropin on the vascular endothelium is through an increase in the expression of endothelial nitric oxide synthase. This article provides an overview of the existing literature about the role of adropin in different pathological conditions.

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“…An interesting study on neuronal nitric oxide synthase (nNOS) expression in pancreatic islets was performed on a rat model. It revealed that nNOS levels in beta cells disappeared after 12 h from the onset of DM [ 52 ].…”

Section: Large Vessel Atherosclerotic Lesion In Dmmentioning

confidence: 99%

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

Mieczkowski

Mrozikiewicz-Rakowska

Kowara

et al. 2022

IJMS

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Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).

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Diabetes Mellitus Alters the Immuno-Expression of Neuronal Nitric Oxide Synthase in the Rat Pancreas

Cited by 5 publications

References 69 publications

Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini

Screening of Amino Acids as a Safe Energy Source for Isolated Rat Pancreatic Acini

Adropin’s Role in Energy Homeostasis and Metabolic Disorders

The Problem of Wound Healing in Diabetes—From Molecular Pathways to the Design of an Animal Model

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