Insulin and the cellular death

2015 ◽  
Vol 9 (2) ◽  
pp. 0-0 ◽  
Author(s):  
Макишева ◽  
R. Makisheva
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Receptors ◽  
Β Cells ◽  
Energy Deficiency ◽  
Protein Energy ◽  
Rapid Flow ◽  
Protection Mechanisms ◽  
Living Organisms ◽  
Main Regulator ◽  
Insulin Overdose

In the review of their own work and the literature it discussed accumulated contradictions of the effect of diabetes mellitus on cell death. The author proposes the concept of the damaging effects of excess insulin on cells with different degrees of sensitivity. The basis for reasoning adopted the following axioms. Insulin is needed by all cells of all living organisms. Insulin is the main regulator of pinocytosis into the cells. Energy and plastic tissue needs increase the number and sensitivity of insulin receptors. Excess insulin occurs when taking stimulants, secretion, degradation of β-cells, insulin overdose. Excess insulin promotes the rapid flow of sub-stances into the cell, then swelling and necrosis. Protection mechanisms against excess hormone are increased binding of insulin, fat cells, insulin resistance and increased growth factors. This leads to reduced apoptosis, ac-celerated angiogenesis, and reduction of the barrier functions of tissues. In diabetes, all the cells are exposed to elevated concentrations of insulin, but most of the cells are damaged endothelium in connection with their regu-lar division. Apoptosis of tissue cells in diabetes mellitus is caused by protein-energy deficiency. Apoptosis of β-cells is necessary to reduce excess insulin.

Therapeutic Approaches to Alzheimer’s Type of Dementia: A Focus on FGF21 Mediated Neuroprotection

2019 ◽  
Vol 25 (23) ◽  
pp. 2555-2568 ◽  
Author(s):  
Rajeev Taliyan ◽  
Sarathlal K. Chandran ◽  
Violina Kakoty
Keyword(s):  
Diabetes Mellitus ◽  
Protein Trafficking ◽  
Metabolic Stress ◽  
Insulin Receptors ◽  
Metabolic Dysfunction ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Endocrine Hormone ◽  
Metabolic Conditions ◽  
The Brain

Neurodegenerative disorders are the most devastating disorder of the nervous system. The pathological basis of neurodegeneration is linked with dysfunctional protein trafficking, mitochondrial stress, environmental factors and aging. With the identification of insulin and insulin receptors in some parts of the brain, it has become evident that certain metabolic conditions associated with insulin dysfunction like Type 2 diabetes mellitus (T2DM), dyslipidemia, obesity etc., are also known to contribute to neurodegeneration mainly Alzheimer’s Disease (AD). Recently, a member of the fibroblast growth factor (FGF) superfamily, FGF21 has proved tremendous efficacy in diseases like diabetes mellitus, obesity and insulin resistance (IR). Increased levels of FGF21 have been reported to exert multiple beneficial effects in metabolic syndrome. FGF21 receptors are present in certain areas of the brain involved in learning and memory. However, despite extensive research, its function as a neuroprotectant in AD remains elusive. FGF21 is a circulating endocrine hormone which is mainly secreted by the liver primarily in fasting conditions. FGF21 exerts its effects after binding to FGFR1 and co-receptor, β-klotho (KLB). It is involved in regulating energy via glucose and lipid metabolism. It is believed that aberrant FGF21 signalling might account for various anomalies like neurodegeneration, cancer, metabolic dysfunction etc. Hence, this review will majorly focus on FGF21 role as a neuroprotectant and potential metabolic regulator. Moreover, we will also review its potential as an emerging candidate for combating metabolic stress induced neurodegenerative abnormalities.

scholarly journals Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (3) ◽  
pp. 1059
Author(s):  
Bodo C. Melnik
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dopaminergic Neurons ◽  
Vagal Nerve ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
The Brain

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.

Erythrocyte Insulin Receptors in Non-insulin-dependent Diabetes Mellitus

Diabetes ◽  
1980 ◽  
Vol 29 (2) ◽  
pp. 96-99 ◽  
Author(s):  
R. DePirro ◽  
A. Fusco ◽  
R. Lauro ◽  
I. Testa ◽  
F. Ferreti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Receptors ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent

A Tale of Two Diseases: Exploring Mechanisms Linking Diabetes Mellitus with Alzheimer’s Disease

2021 ◽  
pp. 1-17
Author(s):  
Jessica Lynn ◽  
Mingi Park ◽  
Christiana Ogunwale ◽  
George K. Acquaah-Mensah
Keyword(s):  
Diabetes Mellitus ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Insulin Receptors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Main Component ◽  
The Impact

Dementias, including the type associated with Alzheimer’s disease (AD), are on the rise worldwide. Similarly, type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic diseases globally. Although mechanisms and treatments are well-established for T2DM, there remains much to be discovered. Recent research efforts have further investigated factors involved in the etiology of AD. Previously perceived to be unrelated diseases, commonalities between T2DM and AD have more recently been observed. As a result, AD has been labeled as “type 3 diabetes”. In this review, we detail the shared processes that contribute to these two diseases. Insulin resistance, the main component of the pathogenesis of T2DM, is also present in AD, causing impaired brain glucose metabolism, neurodegeneration, and cognitive impairment. Dysregulation of insulin receptors and components of the insulin signaling pathway, including protein kinase B, glycogen synthase kinase 3β, and mammalian target of rapamycin are reported in both diseases. T2DM and AD also show evidence of inflammation, oxidative stress, mitochondrial dysfunction, advanced glycation end products, and amyloid deposition. The impact that changes in neurovascular structure and genetics have on the development of these conditions is also being examined. With the discovery of factors contributing to AD, innovative treatment approaches are being explored. Investigators are evaluating the efficacy of various T2DM medications for possible use in AD, including but not limited to glucagon-like peptide-1 receptor agonists, and peroxisome proliferator-activated receptor-gamma agonists. Furthermore, there are 136 active trials involving 121 therapeutic agents targeting novel AD biomarkers. With these efforts, we are one step closer to alleviating the ravaging impact of AD on our communities.

Insulin action and resistance in obesity and noninsulin-dependent type II diabetes mellitus

1982 ◽  
Vol 243 (1) ◽  
pp. E15-E30 ◽  
Author(s):  
J. M. Olefsky ◽  
O. G. Kolterman ◽  
J. A. Scarlett
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Action ◽  
Insulin Receptors ◽  
Tissue Level ◽  
Dependent Diabetes Mellitus ◽  
Target Tissue ◽  
Severe Insulin Resistance ◽  
Glucose Clamp Technique

Resistance to the action of insulin can result from a variety of causes, including the formation of abnormal insulin or proinsulin molecules, the presence of circulating antagonists to insulin or the insulin receptor, or defects in insulin action at the target tissue level. Defects of the latter type are characteristic of obesity and of noninsulin-dependent diabetes mellitus. Analysis of the nature of the insulin resistance in those disorders has been investigated in intact subjects with the use of the euglycemic glucose clamp technique, and both insulin receptors and insulin-mediated glucose metabolism have been studied in adipocytes and monocytes from affected individuals. In both conditions, the cause of insulin resistance is heterogeneous. In some, insulin resistance appears to be due to a defect in the insulin receptor, whereas others have a defect both in the receptor and at the postreceptor level. In both groups, more severe insulin resistance is due to the postreceptor lesion and is correctable with appropriate therapy.

scholarly journals Lack of association between UBE2E2 gene polymorphism (rs7612463) and type 2 diabetes mellitus in a Saudi population.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Khalid Khalaf Alharbi ◽  
Imran Ali Khan ◽  
Yazeed A Al-Sheikh ◽  
Fawiziah Khalaf Alharbi ◽  
Fahad Khalaf Alharbi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Case Control Study ◽  
Saudi Population ◽  
Β Cells ◽  
Pcr Rflp ◽  
Ubiquitin Conjugating Enzyme ◽  
Control Study

The ubiquitin-conjugating enzyme E2E 2 (UBE2E2) gene plays an important role in insulin synthe-sis and secretion under conditions in which stress to the endoplasmic reticu-lum is increased in β-cells. In this case-control study, we have selected rs7612462 polymorphism within UBE2E2 gene to identify in a Saudi population the type 2 diabetes mellitus (T2DM) subjects. In total, 376 subjects with T2DM and 380 controls were enrolled in this study. We have collected 5 mL of peripheral blood from each participant for biochemical and molecular analyses. PCR-RFLP was used to generate genotypes at rs7612462 in all of the study subjects. Clinical data and anthropometric measurements of the patients were significantly different from those of the controls (p

scholarly journals Teucrium polium: Potential Drug Source for Type 2 Diabetes Mellitus

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 128
Author(s):  
Yaser Albadr ◽  
Andrew Crowe ◽  
Rima Caccetta
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Teucrium Polium

The prevalence of type 2 diabetes mellitus is rising globally and this disease is proposed to be the next pandemic after COVID-19. Although the cause of type 2 diabetes mellitus is unknown, it is believed to involve a complex array of genetic defects that affect metabolic pathways which eventually lead to hyperglycaemia. This hyperglycaemia arises from an inability of the insulin-sensitive cells to sufficiently respond to the secreted insulin, which eventually results in the inadequate secretion of insulin from pancreatic β-cells. Several treatments, utilising a variety of mechanisms, are available for type 2 diabetes mellitus. However, more medications are needed to assist with the optimal management of the different stages of the disease in patients of varying ages with the diverse combinations of other medications co-administered. Throughout modern history, some lead constituents from ancient medicinal plants have been investigated extensively and helped in developing synthetic antidiabetic drugs, such as metformin. Teucrium polium L. (Tp) is a herb that has a folk reputation for its antidiabetic potential. Previous studies indicate that Tp extracts significantly decrease blood glucose levels r and induce insulin secretion from pancreatic β-cells in vitro. Nonetheless, the constituent/s responsible for this action have not yet been elucidated. The effects appear to be, at least in part, attributable to the presence of selected flavonoids (apigenin, quercetin, and rutin). This review aims to examine the reported glucose-lowering effect of the herb, with a keen focus on insulin secretion, specifically related to type 2 diabetes mellitus. An analysis of the contribution of the key constituent flavonoids of Tp extracts will also be discussed.

scholarly journals Analysis of the formation of dysglycemia in the substantiation of early pathogenetic therapy of diabetes mellitus

2021 ◽  
pp. 33-44
Author(s):  
L. A. Ruyatkina ◽  
D. S. Ruyatkin ◽  
I. S. Iskhakova
Keyword(s):  
Diabetes Mellitus ◽  
Postmenopausal Women ◽  
Metabolic Memory ◽  
Β Cells ◽  
Insulin Sensitizer ◽  
Dipeptidyl Peptidase 4 ◽  
Group 2 ◽  
Glucose Lowering Therapy ◽  
Secretory Capacity ◽  
Hba1c Levels

Introduction. To control carbohydrate metabolism disorders (CMD), which are closely related to the effect on the prognosis of cardiovascular diseases (CVD), their early, pathogenetically substantiated and prognosis-oriented therapy is required with a view to positive metabolic memory. The choice of drugs is based on the analysis of the formation of pre-nosological CMD - variants of prediabetes. The indices of the homeostatic model HOMA and the TyG family are most often used to assess the main links in the pathogenesis of CMD, IR and the secretory capacity of β-cells.Objective: to assess the basic pathogenetic links in prenosological CMD in comparison with type 2 diabetes mellitus (DM2) using a cohort of postmenopausal women: parameters of IR and secretory capacity of β-cells according to the TyG and HOMA-2 indices. Materials and methods. The examined 94 postmenopausal women 58.0 (53.0; 63.0) years old were divided into groups by history and HbA1c levels (%). Group 1 consisted of patients with T2DM (7.20: 6.60; 7.98) with a duration of 4.0 (2.0; 7.0) years; women with two-fold fasting normoglycemia without a history of CMD were classified according to their HbA1c levels into group 2 (prediabetes) and 3 (without CMD) twice: according to WHO criteria - 6.15 (6.03; 6.30) and 5.45 (5.20; 5.80); and ADA - 6.00 (5.80; 6.23) and 5.35 (5.05; 5.40), respectively. The indices TyG, HOMA2-IR, HOMA2-%S, and HOMA2-%B were determined (based on C-peptide calculations).Results and discussion. The performed analysis confirms the contribution of IR/insulin sensitivity to the progression of CMD with the participation of the phenomenon of lipoglucotoxicity at the prenosological stage of their formation, starting with HbA1c ≥ 5.7% levels. The inadequate secretory response of β-cells reflects an early decline in their functional abilities even at the stage of prediabetes. This limits the effectiveness of the classical stepwise scheme for intensifying glucose-lowering therapy with a T2DM duration of less than 10 years.Conclusions. Along with the timely diagnosis of dysglycemia, to control the cardiometabolic risk, it is advisable to use drug combinations early in terms of their effect on the key links in the pathogenesis of CMD: insulin resistance and β-cell dysfunction. Pioglitazone has been substantiated as an insulin sensitizer, which has a proven effect on the regression of early CMD and a decrease in the risk of cardiovascular events. In order to eliminate incretin dysfunction, which is closely related to the adequacy of the secretory capabilities of β-cells to the needs of impaired glucose homeostasis, a rational combination with an inhibitor of dipeptidyl peptidase-4.

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