scholarly journals DR3 stimulation of adipose resident ILC2s ameliorates type 2 diabetes mellitus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Pedram Shafiei-Jahani ◽  
Benjamin P. Hurrell ◽  
Lauriane Galle-Treger ◽  
Doumet Georges Helou ◽  
Emily Howard ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Death Receptor ◽  
Lymphoid Cells ◽  
Low Grade ◽  
Group 2

Abstract Disturbances in glucose homeostasis and low-grade chronic inflammation culminate into metabolic syndrome that increase the risk for the development of type 2 diabetes mellitus (T2DM). The recently discovered group 2 innate lymphoid cells (ILC2s) are capable of secreting copious amounts of type 2 cytokines to modulate metabolic homeostasis in adipose tissue. In this study, we have established that expression of Death Receptor 3 (DR3), a member of the TNF superfamily, on visceral adipose tissue (VAT)-derived murine and peripheral blood human ILC2s is inducible by IL-33. We demonstrate that DR3 engages the canonical and/or non-canonical NF-κB pathways, and thus stimulates naïve and co-stimulates IL-33-activated ILC2s. Importantly, DR3 engagement on ILC2s significantly ameliorates glucose tolerance, protects against insulin-resistance onset and remarkably reverses already established insulin-resistance. Taken together, these results convey the potent role of DR3 as an ILC2 regulator and introduce DR3 agonistic treatment as a novel therapeutic avenue for treating T2DM.

scholarly journals Effects of exercise training on inflammasome-related mediators and their associations to glucometabolic variables in patients with combined coronary artery disease and type 2 diabetes mellitus: Sub-study of a randomized control trial

2019 ◽  
Vol 16 (4) ◽  
pp. 360-368
Author(s):  
Hani Zaidi ◽  
Rune Byrkjeland ◽  
Ida U Njerve ◽  
Sissel Åkra ◽  
Svein Solheim ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Coronary Artery Disease ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Exercise Training ◽  
Artery Disease

Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.

scholarly journals Influence of metabolic disorders on phenotypic modulation of vascular endothelium in type 2 diabetes mellitus

2017 ◽  
Vol 70 (11-12) ◽  
pp. 437-443
Author(s):  
Romana Mijovic ◽  
Branislava Ilincic ◽  
Suncica Kojic-Damjanov ◽  
Biljana Vuckovic ◽  
Radmila Zeravica ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Adhesion Molecules ◽  
Vascular Endothelium ◽  
Low Grade ◽  
Phenotypic Modulation

Introduction. Endothelium is a dynamic, strategically positioned defensive regulator of vascular homeostasis. Physiology and Pathophysiology of Vascular Endothelium. Endothelial phenotypic modulation involves five basic characteristics: the expression of leukocyte adhesion molecules, the production of cytokines, change in the shape and the permeability of the endothelium, prothrombotic changes and upregulation of autoantigens. Obesity, Metabolic Inflammation and Vascular Endothelium One of the most important pathophysiological manifestations of adiposopathy may be the phenotypic conversion of vascular endothelium. Insulin Resistance and Vascular Endothelium. Under the conditions of insulin resistance and consequent hyperinsulinemia, there is imbalance between the production of endothelial vasoconstrictors and vasodilators, increased expression of adhesion molecules, and platelet hyperreactivity. Hyperglycemia and Vascular Endothelium. Hyperglycemia causes endothelial dysfunction by various mechanisms that involve activation of polyol pathway and production of sorbitol, increased formation of advanced glycation end products, activation of various isoforms of protein kinase C and activation of hexosamine pathway. Dyslipidemia and vascular endothelium. Dyslipidemia takes an important role in a cascade of pathophysiological processes that result in endothelial activation and chronic dysfunction. Conclusion. Hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, visceral obesity and low-grade inflammation are the main factors responsible for development of endothelial dysfunction in type 2 diabetes mellitus.

scholarly journals Association of Serum Adipokines Levels with Glycemic Control and Metabolic Dyslipidemia in Sudanese Patients with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Halima Babiikir Eltahir ◽  
Elmahadi Mohamed Ali ◽  
Abdelrahim Osman Mohamed
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Glycemic Control ◽  
Total Cholesterol ◽  
Pearson Correlation ◽  
P Value

Abstract Background:The pathogenesis of type 2 diabetes mellitus is due to two major abnormalities including insulin resistance and dysfunction, which lead to the inability to regulate blood glucose level. Adiponectin is a hormone secreted by the adipose tissue and it takes part in glucose metabolism with insulin-sensitising properties. Low levels of adiponectin leads to reduction of fatty acid oxidation decreased glucose uptake in skeletal muscle cells and increased level of free fatty acids leading to insulin resistance. Leptin is another adipokine produced by adipose tissue involved in the control of food intake via its action on the hypothalamus, suppressing appetite and stimulating energy expenditure. Leptin plays a critical role in pathophysiology of type 2 diabetes mellitus.The aim of the study was to investigate the association of serum adipokines levels with glycemic control and metabolic dyslipidemia in Sudanese patients with type 2 diabetes mellitus.Methods: This was a case control study. 202 patients with type 2 diabetes and 102 non-diabetic controls participated after signing written consent. Weight (kg) and height (m) were measured thenthe body mass index (kg/m2) was determined. Blood samples were collected after an overnight fasting. FBG, HbA1c and lipid profiles were measured using enzymatic methods. Adiponectin and leptin were measured using sandwich ELISA.Results: Adiponectin concentrations was significantly lower in patients with type 2 diabetes compared with the controls (p<0.001) and it was inversely correlated with HbA1c (Pearson Correlation -.160, P value = 0.005), total cholesterol and LDL levels (P = 0.05) and direct correlated HDL levels (P = 0.05). Leptin concentrations was significantly higher in patients with type 2 diabetes compared with the controls (p<0.002) and it was positively correlated with HbA1c (Pearson Correlation .155, P value = 0.02), total cholesterol and LDL levels (P = 0.05), there were no correlation with HDL and TG levels. Patients had significantly higher fasting blood glucose, HbA1c levels, total cholesterol and LDL levels compared with the controls. Conclusion: Patients with type 2 diabetes mellitus had decreased levels of serum adiponectin, high levels of serum leptin. There were significant correlations found between adiponectin and leptin levels with glycemic control and metabolic dyslipidemia

scholarly journals Fatty acid metabolism in obesity and type 2 diabetes mellitus

2003 ◽  
Vol 62 (3) ◽  
pp. 753-760 ◽  
Author(s):  
E. E. Blaak
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Acid Oxidation ◽  
Acid Uptake

Disturbances in pathways of lipolysis and fatty acid handling are of importance in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that a lowered catecholamine-mediated lipolytic response may play a role in the development and maintenance of increased adipose tissue stores. Increased adipose tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high lipolytic rate may increase circulating NEFA concentrations, which may promote insulin resistance and cardiovascular complications. In addition, a disturbance of NEFA uptake by adipose tissue postprandially is also a critical determinant of plasma NEFA concentration. Furthermore, evidence is increasing that insulin-resistant muscle is characterised by a lowered ability to oxidise fatty acids. A dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a factor promoting accumulation of lipid intermediates and triacylglycerols within skeletal muscle, which is strongly associated with skeletal muscle insulin resistance. The present review describes the reported disturbances in pathways of lipolysis and skeletal muscle fatty acid handling, and discusses underlying mechanisms and metabolic consequences of these disturbances.

scholarly journals The joint effect of congenital hypothyroidism and hypercaloric diet consumption as triggers of type 2 diabetes mellitus

2022 ◽  
Vol 11 (1) ◽  
Author(s):  
Jorge Alberto Tapia-Martínez ◽  
Margarita Franco-Colín ◽  
Vanessa Blas-Valdivia ◽  
Edgar Cano-Europa
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Cardiovascular Risk ◽  
Glucose Tolerance ◽  
Congenital Hypothyroidism ◽  
Hypercaloric Diet

Introduction Congenital hypothyroidism affects metabolic and thyroid programming, having a deleterious effect on bodyweight regulation promoting metabolic diseases. This work aimed to demonstrate the development of type 2 diabetes mellitus (T2D) in animals with congenital hypothyroidism, only by the consumption of a mild hypercaloric diet in the extrauterine stage. Methods Two groups of female Wistar rats (n  = 9): euthyroid and hypothyroid were used. Hypothyroidism was induced by a thyroidectomy with parathyroid reimplantation. Male offsprings post-weaning were divided into four groups (n  = 10): euthyroid, hypothyroid, euthyroid + hypercaloric diet, and hypothyroid + hypercaloric diet. The hypercaloric diet consisted of ground commercial feed plus 20% lard and was administered until postnatal week 40. Bodyweight and energy intake were monitored weekly. Also, metabolic and hormonal markers related to cardiovascular risk, insulin resistance, and glucose tolerance were analyzed at week 40. Then, animals were sacrificed to perform the morphometric analysis of the pancreas and adipose tissue. Results T2D was developed in animals fed a hypercaloric diet denoted by the presence of central obesity, hyperphagia, hyperglycemia, dyslipidemia, glucose tolerance, insulin resistance and hypertension, as well as changes in the cytoarchitecture of the pancreas and adipose tissue related to T2D. The results show that congenital hypothyroid animals had an increase in metabolic markers and an elevated cardiovascular risk. Conclusions Congenital hypothyroid animals develop T2D, having the highest metabolic disturbances and a worsened clinical prognosis than euthyroid animals.

scholarly journals The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chainn-3 PUFA

2010 ◽  
Vol 69 (2) ◽  
pp. 232-243 ◽  
Author(s):  
Elizabeth Oliver ◽  
Fiona McGillicuddy ◽  
Catherine Phillips ◽  
Sinead Toomey ◽  
Helen M. Roche
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Receptor ◽  
Insulin Signalling ◽  
Serine Phosphorylation ◽  
Therapeutic Effects ◽  
Low Grade

The WHO estimate that >1×106deaths in Europe annually can be attributed to diseases related to excess body weight, and with the rising global obesity levels this death rate is set to drastically increase. Obesity plays a central role in the metabolic syndrome, a state of insulin resistance that predisposes patients to the development of CVD and type 2 diabetes mellitus. Obesity is associated with low-grade chronic inflammation characterised by inflamed adipose tissue with increased macrophage infiltration. This inflammation is now widely believed to be the key link between obesity and development of insulin resistance. In recent years it has been established that activation of pro-inflammatory pathways can cross talk with insulin signalling pathways via a number of mechanisms including (a) down-regulation of insulin signalling pathway proteins (e.g. GLUT4 and insulin receptor substrate (IRS)-1), (b) serine phosphorylation of IRS-1 blocking its tyrosine phosphorylation in response to insulin and (c) induction of cytokine signalling molecules that sterically hinder insulin signalling by blocking coupling of the insulin receptor to IRS-1. Long-chain (LC)n-3 PUFA regulate gene expression (a) through transcription factors such as PPAR and NF-κB and (b) via eicosanoid production, reducing pro-inflammatory cytokine production from many different cells including the macrophage. LCn-3 PUFA may therefore offer a useful anti-inflammatory strategy to decrease obesity-induced insulin resistance, which will be examined in the present review.

scholarly journals Association of Serum Adipokines Levels with Glycemic Control and Metabolic Dyslipidemia in Sudanese Patients with Type 2 Diabetes Mellitus

2020 ◽  
Author(s):  
Halima Babiikir Eltahir ◽  
Elmahdi Mohamed Ali ◽  
Abdelrahim Osman Mohamed
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Glycemic Control ◽  
Total Cholesterol ◽  
Pearson Correlation ◽  
P Value

Abstract Background: The pathogenesis of type 2 diabetes mellitus is due to two major abnormalities including insulin resistance and dysfunction, which lead to the inability to regulate blood glucose level. Adiponectin is a hormone secreted by the adipose tissue and it takes part in glucose metabolism with insulin-sensitising properties. Low levels of adiponectin leads to reduction of fatty acid oxidation decreased glucose uptake in skeletal muscle cells and increased level of free fatty acids leading to insulin resistance. Leptin is another adipokine produced by adipose tissue involved in the control of food intake via its action on the hypothalamus, suppressing appetite and stimulating energy expenditure. Leptin plays a critical role in pathophysiology of type 2 diabetes mellitus.The aim of the study was to investigate the association of serum adipokines levels with glycemic control and metabolic dyslipidemia in Sudanese patients with type 2 diabetes mellitus.Methods: This was a case control study. 202 patients with type 2 diabetes and 102 non-diabetic controls participated after signing written consent. Weight (kg) and height (m) were measured then the body mass index (kg/m2) was determined. Blood samples were collected after an overnight fasting. FBG, HbA1c and lipid profiles were measured using enzymatic methods. Adiponectin and leptin were measured using sandwich ELISA.Results: Adiponectin concentrations was significantly lower in patients with type 2 diabetes compared with the controls (p<0.001) and it was inversely correlated with HbA1c (Pearson Correlation -.160, P value = 0.005), total cholesterol and LDL levels (P = 0.05) and direct correlated HDL levels (P = 0.05). Leptin concentrations was significantly higher in patients with type 2 diabetes compared with the controls (p<0.002) and it was positively correlated with HbA1c (Pearson Correlation .155, P value = 0.02), total cholesterol and LDL levels (P = 0.05), there were no correlation with HDL and TG levels. Patients had significantly higher fasting blood glucose, HbA1c levels, total cholesterol and LDL levels compared with the controls.Conclusion: Patients with type 2 diabetes mellitus had decreased levels of serum adiponectin, high levels of serum leptin. There were significant correlations found between adiponectin and leptin levels with glycemic control and metabolic dyslipidemia .

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