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Current Diabetes Reports Aug 2017Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR... (Review)
Review
PURPOSE OF REVIEW
Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model.
RECENT FINDINGS
Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. DR results in vascular changes and dysfunction of the neural, glial, and pancreatic β cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.
Topics: Animals; Cytokines; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Disease Models, Animal; Humans; Hypoxia; Models, Genetic
PubMed: 28836097
DOI: 10.1007/s11892-017-0913-0 -
Laboratory Animal Research Aug 2021Diabetes mellitus, a very common and multifaceted metabolic disorder is considered as one of the fastest growing public health problems in the world. It is characterized... (Review)
Review
Diabetes mellitus, a very common and multifaceted metabolic disorder is considered as one of the fastest growing public health problems in the world. It is characterized by hyperglycemia, a condition with high glucose level in the blood plasma resulting from defects in insulin secretion or its action and in some cases both the impairment in secretion and also action of insulin coexist. Historically, animal models have played a critical role in exploring and describing malady pathophysiology and recognizable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we reviewed the experimental models employed for diabetes and for its related complications. This paper reviews briefly the broad chemical induction of alloxan and streptozotocin and its mechanisms associated with type 1 and type 2 diabetes. Also we highlighted the different models in other species and other animals.
PubMed: 34429169
DOI: 10.1186/s42826-021-00101-4 -
Journal of Medicine and Life Mar 2022This study aimed to evaluate metformin as a widely used oral hypoglycemic agent and identify the effects on biochemical and antioxidant body systems of rabbits. Four...
This study aimed to evaluate metformin as a widely used oral hypoglycemic agent and identify the effects on biochemical and antioxidant body systems of rabbits. Four groups of rabbits were randomly allocated as the control, the alloxan-induced diabetic, metformin-treated, and alloxan treated with metformin. The results revealed that alloxan leads to significant elevation in glucose (Glc) levels, malondialdehyde (MDA), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), triglycerides (TGs), and total cholesterol (TCH), and a significant decline in high-density lipoprotein (HDL) and glutathione (GSH) as compared with the control group. Metformin alone caused a significant decline in Glc and HDL with significant elevation in LDL and MDA without significant changes in TCH, TGs, VLDL, and GSH. When metformin was offered as a treatment for alloxan-induced diabetic animals, it caused a significant decline in Glc, TCH, TGs, LDL, and VLDL levels with significant elevation in GSH and without a significant change in HDL and MDA. Metformin causes a decline in glucose levels due to its ability to decrease the use of substances hepatic cells use to create glucose and its ability to induce the enzymes participating in glucose oxidation.
Topics: Animals; Rabbits; Alloxan; Diabetes Mellitus, Experimental; Glutathione; Hypoglycemic Agents; Metformin
PubMed: 35450001
DOI: 10.25122/jml-2021-0417 -
Pharmaceutical Biology Dec 2021Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.
CONTEXT
Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation.
OBJECTIVE
The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of .
MATERIALS AND METHODS
Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats ( = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay.
RESULTS
Methanol extracts of leaves and bark, and the aqueous extract of leaves of , caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively.
DISCUSSION AND CONCLUSIONS
The methanol bark extract of showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.
Topics: Alloxan; Animals; Antioxidants; Bangladesh; Blood Glucose; Diabetes Mellitus, Experimental; Glyburide; Hypoglycemic Agents; Models, Animal; Moraceae; Plant Bark; Plant Extracts; Rats; Rats, Wistar
PubMed: 34365913
DOI: 10.1080/13880209.2021.1954668 -
Ancient Science of Life 2017Over the last century, human life style and food habits have drastically changed which lead to various chronic diseases. Diabetes mellitus is one such disease which is... (Review)
Review
BACKGROUND
Over the last century, human life style and food habits have drastically changed which lead to various chronic diseases. Diabetes mellitus is one such disease which is causing serious problems to human health. Allopathic drugs are not much effective in handling the disease and its complications. Hence focus has been turned towards the traditional system of medicine. Medicinal plants play an important role in the management of diabetes mellitus.
METHODS
Experimental studies conducted on species of Artemisia on diabetic animal models and human published since the year 2000 until April, 2017 were reviewed. Each article was critically appraised by two independent reviewers for their methodological quality using the JBIMAStARI tool.
RESULT
A total of 14 studies were included in this review and the blood glucose data obtained from these critically reviewed studies clearly showed that both the aqueous and alcoholic extracts of species of Artemisia produced significant hypoglycemic effects in alloxan, Streptozotocin and high fat diet induced diabetic animals and diabetic humans with different mechanisms of action as compared to standard antidiabetic medications.
DISCUSSION AND CONCLUSION
The antidiabetic effect of single or multiple doses of aqueous and alcoholic extracts of Artemisia species was due to the active compounds of these plants and they all are effective in lessening the blood glucose level in all of those experimental studies. Despite the presence of known antidiabetic medicines in the pharmaceutical market, therapeutic remedies from these medicinal plants have been utilized with success to treat this disorder and its complications with a relatively less side effects.
PubMed: 29269967
DOI: 10.4103/asl.ASL_87_17 -
Frontiers in Endocrinology 2023Various animal and cell culture models of diabetes mellitus (DM) have been established and utilized to study diabetic peripheral neuropathy (DPN). The divergence of... (Review)
Review
Various animal and cell culture models of diabetes mellitus (DM) have been established and utilized to study diabetic peripheral neuropathy (DPN). The divergence of metabolic abnormalities among these models makes their etiology complicated despite some similarities regarding the pathological and neurological features of DPN. Thus, this study aimed to review the omics approaches toward DPN, especially on the metabolic states in diabetic rats and mice induced by chemicals (streptozotocin and alloxan) as type 1 DM models and by genetic mutations (MKR, db/db and ob/ob) and high-fat diet as type 2 DM models. Omics approaches revealed that the pathways associated with lipid metabolism and inflammation in dorsal root ganglia and sciatic nerves were enriched and controlled in the levels of gene expression among these animal models. Additionally, these pathways were conserved in human DPN, indicating the pivotal pathogeneses of DPN. Omics approaches are beneficial tools to better understand the association of metabolic changes with morphological and functional abnormalities in DPN.
Topics: Humans; Mice; Rats; Animals; Diabetic Neuropathies; Diabetes Mellitus, Experimental; Sciatic Nerve; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1
PubMed: 38089620
DOI: 10.3389/fendo.2023.1208441 -
Lipids in Health and Disease Aug 2022Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α...
Syntaxin regulates pancreatic β cell mass and participates in insulin secretion by regulating insulin exocytosis. In addition, syntaxin 4 reduces IFNγ and TNF-α signaling via NF-ĸB in islet β-cells that facilitates plasma glucose sensing and appropriate insulin secretion. Arachidonic acid (AA) has potent anti-inflammatory actions and prevents the cytotoxic actions of alloxan and streptozotocin (STZ) against pancreatic β cells and thus, prevents the development of type 1 diabetes mellitus (induced by alloxan and STZ) and by virtue of its anti-inflammatory actions protects against the development of type 2 diabetes mellitus (DM) induced by STZ in experimental animals that are models of type 1 and type 2 DM in humans. AA has been shown to interact with syntaxin and thus, potentiate exocytosis. AA enhances cell membrane fluidity, increases the expression of GLUT and insulin receptors, and brings about its anti-inflammatory actions at least in part by enhancing the formation of its metabolite lipoxin A4 (LXA4). Prostaglandin E2 (PGE2), the pro-inflammatory metabolite of AA, activates ventromedial hypothalamus (VMH) neurons of the hypothalamus and inhibits insulin secretion leading to reduced glucose tolerance and decreases insulin sensitivity in the skeletal muscle and liver. This adverse action of PGE2 on insulin release and action can be attributed to its (PGE2) pro-inflammatory action and inhibitory action on vagal tone (vagus nerve and its principal neurotransmitter acetylcholine has potent anti-inflammatory actions). High fat diet fed animals have hypothalamic inflammation due to chronic elevation of PGE2. Patients with type 2 DM show low plasma concentrations of AA and LXA4 and elevated levels of PGE2. Administration of AA enhances LXA4 formation without altering or reducing PGE2 levels and thus, tilts the balance more towards anti-inflammatory events. These results suggest that administration of AA is useful in the prevention and management of DM by enhancing the action of syntaxin, increasing cell membrane fluidity, and reducing VMH inflammation. Docosahexaenoic acid (DHA) has actions like AA: it increases cell membrane fluidity; has anti-inflammatory actions by enhancing the formation of its anti-inflammatory metabolites resolvins, protectins and maresins; interacts with syntaxin and enhance exocytosis in general and of insulin. But the DHA content of cell membrane is lower compared to AA and its content in brain is significant. Hence, it is likely DHA is important in neurotransmitters secretion and regulating hypothalamic inflammation. It is likely that a combination of AA and DHA can prevent DM.
Topics: Alloxan; Animals; Anti-Inflammatory Agents; Arachidonic Acid; Diabetes Mellitus, Type 2; Dinoprostone; Docosahexaenoic Acids; Humans; Inflammation; Insulins; Qa-SNARE Proteins; Streptozocin
PubMed: 35982452
DOI: 10.1186/s12944-022-01681-3 -
ACS Omega Feb 2022Alloxan is a chemical generally administered to rats to induce diabetes mellitus, and pharmaceutical industries test the efficacy of their diabetic products on these...
Alloxan is a chemical generally administered to rats to induce diabetes mellitus, and pharmaceutical industries test the efficacy of their diabetic products on these rats. Alloxan is in a redox cycle with dialuric acid; hence, direct estimation of alloxan may not represent the actual concentration of the same in a given matrix. Also, in recent times, alloxan is added to food materials, especially to the all-purpose flour (maida) to bring softness and white color to the flour. Hence, consumption of food items made from such flour could induce diabetic mellitus in individuals, making it imperative to develop an accurate estimation of alloxan in food items. Herein, a voltammetric-based technique is developed to quantify the alloxan in refined wheat flour (maida) using an unmodified glassy carbon electrode (GCE). The electrochemical method offers rapid sensing while the use of an unmodified GCE surface offers repeatability and reproducibility between measurements. First, alloxan is converted to its stable adduct alloxazine by the reaction with -phenylenediamine. The alloxazine adduct is electrochemically active, and the concentration of alloxan is estimated as a function of alloxazine formed using the voltammetric technique. The common shortfall in alloxan detection mainly involves its short half-life (∼a minute) whereas the alloxazine adduct formed is stable over a period of time. Using the current approach, alloxan concentration ranging from 10 to 600 μM is detected with a sensitivity of 0.0116 μA/μM. A low limit of detection of 1.95 μM with a precision of 1.2% is achieved using the above method. Real sample analysis revealed the presence of alloxan in all-purpose flour (maida-refined wheat flour) and bread purchased from the local market to the values of 35.76 and 25.03 μM, respectively. The same is confirmed using the gold-standard colorimetric technique.
PubMed: 35224361
DOI: 10.1021/acsomega.1c06313 -
BioMed Research International 2022Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic -cell disruption and hyperglycemia. Therefore, it is necessary to...
Type 1 diabetes mellitus (T1DM) is a chronic disease represented by insulin-causing pancreatic -cell disruption and hyperglycemia. Therefore, it is necessary to establish a variety of animal models of diabetes to study the pathogenesis and pathophysiology of it. However, there are few reports on the use of beagle dogs to establish an animal model of type 1 diabetes. This study aimed to explore a simple and feasible modeling method to establish a long-term and stable type 1 diabetes model in beagle dogs. Forty adult beagle dogs were randomly divided into control group and model group. After 24 h of fasting, streptozotocin (20 mg/kg) and alloxan (20 mg/kg) were injected through the cephalic vein. The second intravenous injection was given on the 4th day after the first injection. Insulin release testing was performed on the 7th day after the last intravenous injection. Fasting blood glucose and body weight were recorded monthly. Four months after the last injection, the serum fructosamine content and the ratio of glycated hemoglobin were detected. Then, the pancreatic tissue was harvested for histopathological examination. The results showed that the level of fasting blood glucose of the 16 dogs in the model group was consistently higher than 11.1 mmol/L for 4 consecutive months. Moreover, compared with the control group, the insulin release curve of the model group was flat with no increase. The body weight of the model group was significantly reduced, and the ratios of blood glucose, fructosamine, and glycosylated hemoglobin were significantly higher than those in the control group. Meanwhile, histopathological examination of the pancreas showed that the islet beta cells appeared to have vacuoles or even necrosis. In the model group, pancreatic -cells were damaged and insulin release was reduced. These results suggest that the above modeling methods can induce long-term and stable type 1 diabetes models in beagle dogs.
Topics: Alloxan; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 1; Dogs; Fructosamine; Insulin; Streptozocin
PubMed: 35978645
DOI: 10.1155/2022/5422287 -
Cells Feb 2022Oxidative stress caused by the exposure of pancreatic ß-cells to high levels of fatty acids impairs insulin secretion. This lipotoxicity is thought to play an important...
Oxidative stress caused by the exposure of pancreatic ß-cells to high levels of fatty acids impairs insulin secretion. This lipotoxicity is thought to play an important role in ß-cell failure in type 2 diabetes and can be prevented by antioxidants. Gamma-hydroxybutyrate (GHB), an endogenous antioxidant and energy source, has previously been shown to protect mice from streptozotocin and alloxan-induced diabetes; both compounds are generators of oxidative stress and yield models of type-1 diabetes. We sought to determine whether GHB could protect mouse islets from lipotoxicity caused by palmitate, a model relevant to type 2 diabetes. We found that GHB prevented the generation of palmitate-induced reactive oxygen species and the associated lipotoxic inhibition of glucose-stimulated insulin secretion while increasing the NADPH/NADP+ ratio. GHB may owe its antioxidant and insulin secretory effects to the formation of NADPH.
Topics: Animals; Antioxidants; Diabetes Mellitus, Type 2; Islets of Langerhans; Mice; NADP; Palmitates; Sodium Oxybate
PubMed: 35159354
DOI: 10.3390/cells11030545