Glucose Metabolism In Type 2 Diabetes Mellitus Research Articles

The regulatory role of erythropoietin in diabetes mellitus: a focus on oxidative and glycemic statuses

Background and objectives. One of the leading causes of disability and death among the population is type 2 diabetes mellitus (T2DM), which is characterized by persistent hyperglycemia. The disease is associated with disorders including oxidative stress and resistance to insulin action, which are involved in the progression of other diabetic complications. Such complications strongly rationalize the need for advanced treatment strategies. Considering the antioxidant, and anti-inflammatory in addition to cytoprotective properties of erythropoietin (EPO), it may offer a new potential strategy for the management of these disorders in diabetic patients. This review aims to explore the effects of EPO on oxidative stress and insulin resistance and its impact on glucose metabolism to guide healthcare professionals to a novel approach for controlling diabetes complications. Materials and methods. This review was conducted by analyzing studies involved with oxidative stress, resistance to insulin, and glucose metabolism in T2DM published in Cochran Library, PubMed, and Google Scholar until February 2024. Results. EPO shows promising beneficial effects in the management of these diabetes-associated disorders. Conclusion. With this beneficial effect of EPO, it is considered a strong candidate and area of development for the creation of new choices in the management of diabetes.

Ginsenoside Rb1 ameliorates the abnormal hepatic glucose metabolism by activating STAT3 in T2DM mice

Ginsenoside Rb1, a major bioactive component of Panax ginseng C. A. Mey., exerts beneficial effects on type 2 diabetes mellitus (T2DM), but its underlying mechanism is unclear. STAT3 is a key factor regulating energy metabolism. Herein, we tested whether Rb1 regulates STAT3-controlled hepatic glucose metabolism to ameliorate T2DM. Rb1 ameliorated abnormal hepatic glucose metabolism, insulin resistance, and liver steatosis in T2DM mice. Hepatic STAT3 phosphorylation was decreased in T2DM and increased after Rb1 treatment. Moreover, Rb1 reversed the decreased expressions of glycolytic enzymes and the increased expressions of gluconeogenic enzymes in T2DM. STAT3 activation increased the expressions of glycolytic enzymes and decreased the expressions of gluconeogenic enzymes in vitro, and vice versa. Further, STAT3 inhibition reversed the changes of these enzymes induced by Rb1 in insulin-resistant cells. Taken together, Rb1 ameliorated abnormal hepatic glucose metabolism in T2DM in a STAT3-dependent manner, which provides experimental bases for Rb1 in treating T2DM.

Lactobacillus casei LC89 exerts antidiabetic effects through regulating hepatic glucagon response and gut microbiota in type 2 diabetic mice.

Previous study suggests that Lactobacillus casei exhibits antihyperglycemic activity, however, the molecular mechanism of this has yet to be elucidated. Here, the anti-diabetic effects and underlying mechanisms of Lactobacillus casei LC89 are investigated in type 2 diabetes mellitus (T2DM) mice, which was induced by a high-fat diet (HFD) with streptozotocin (100 mg per kg BW). The results show that LC89 at a dose of 109 CFU day-1 decreases fasting blood glucose (FBG) and insulin levels by 35.12% and 28.37%, respectively, compared to the diabetes control (DC) group. Moreover, LC89 treatment improved the insulin resistance index (HOMA-IR), serum lipid profiles and inflammation cytokines. The real-time polymerase chain reaction indicated that LC89 markedly downregulates the mRNA expression of hepatic glucagon (GCG), glucagon receptor (GCGR), phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). Meanwhile, LC89 significantly decreases the abundance of Odoribacter, but increases the Alloprevotella, Bacteroides, Parabacteroides and Ruminococcus content. Therefore, LC89 plays a positive role in alleviating T2DM by regulating gut microbiota and glucagon signal pathway-related genes, and it may be a beneficial dietary supplement to regulate glucose metabolism in T2DM.

Elevated serum lipocalin 2 levels are associated with indexes of both glucose and bone metabolism in type 2 diabetes mellitus.

The role of lipocalin 2 (LCN2) in type 2 diabetes mellitus (T2DM) needs to be fully elucidated. Moreover, bone has been demonstrated to modulate glucose metabolism via LCN2. We thus performed this study to investigate the associations of LCN2 with indexes of glucose metabolism in T2DM. The associations of LCN2 with bone metabolism were examined concurrently. Total 288 Chinese Han subjects entered in this study including 146 patients with T2DM and 142 subjects with normal glucose tolerance. Insulin resistance was assessed by HOMA-IR and.

Duodenum Exclusion Alone Is Sufficient to Improve Glucose Metabolism in STZ-Induced Diabetes Rats.

Several studies have found that metabolic surgery can significantly improve glucose homeostasis; however, the intrinsic mechanisms remain unclear. Accumulating evidence suggests that duodenal bypass plays a crucial role in the treatment of type 2 diabetes mellitus (T2DM). Here, we aimed to evaluate the effect of duodenal reflux on glucose metabolism in T2DM. A high-fat diet and low-dose streptozotocin (STZ) administration were used to induce T2DM in male rats, which were assigned to three experimental groups: sham operation (SO; n = 10), new duodenal-jejunal bypass (NDJB; n = 10), and new duodenal-jejunal bypass with a tube (NDJBT; n = 10). Weight, food intake, oral glucose tolerance test (OGTT) results, glucagon-like peptide 1 (GLP-1) levels, and histopathology were assessed before or after surgery. Plain abdominal radiography was performed 1week after the operation. Plain abdominal radiography indicated the occurrence of contrast agent reflux into the duodenum. The body weight and food intake in all three groups did not significantly differ before and after surgery. The NDJB and particularly the NDJBT groups exhibited better glucose tolerance, lower fasting blood glucose (FBG) levels, lower area under the curves for OGTT (AUCOGTT) values, and higher GLP-1 levels, as compared with the sham group postoperatively. The villus height and crypt depth were both shorter in the biliopancreatic limb after NDJBT, as compared with those after SO and NDJB. Thus, exclusion of the duodenum alone and tube placement can effectively prevent duodenal reflux and improve glucose homeostasis, which further suggests that the duodenum plays an important role in T2DM.

β-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling

Type 2 diabetes mellitus (T2DM) is a common metabolic disease worldwide. It has been reported that irisin play regulatory role in glucose metabolism in T2DM. However, the underlying mechanism involved in that is not completely known. Herein, we determined the novel role of β-arrestin-2 in irisin-induced glucose utilization in diabetes. Effects of irisin and β-arrestin-2 on glucose utilization were investigated in a rat model of diabetes and in diabetic C2C12 cells in vitro. Results showed that irisin had positive role in glucose metabolism via regulating glucose tolerance as well as uptake in cardiac and skeletal muscle tissues, as evidenced by IPGTT, 2-deoxyglucose uptake and plasma membrane GLUT-4 assay. β-arrestin-2 also improved glucose utilization in diabetes by increasing the glucose uptake and insulin sensitivity, as shown in mice overexpressing β-arrestin-2. In diabetic C2C12 myocytes, irisin-induced GLUT4 and glucose uptake were restrained by β-arrestin-2 inhibition, but was enhanced by β-arrestin-2 overexpression. Additionally, irisin and β-arrestin-2 increased the activation of p38 MAPK in diabetic C2C12 cells, and the repression of p38 MAPK activation decreased the glucose uptake and plasma membrane GLUT-4 was enhanced by irisin and β-arrestin-2 overexpression in diabetic C2C12 cells. In conclusion, we demonstrated that β-arrestin-2 has a crucial role in irisin induced glucose metabolism in T2DM by regulating the p38 MAPK signaling. This might present a novel therapeutic target of treatment for human diabetes.

Dyslipidaemia in type 2 diabetes mellitus: bad for the heart.

Type 2 diabetes mellitus (T2DM) is associated with increased coronary heart disease (CHD) morbidity and mortality. These patients are also more prone to heart failure, arrhythmias and sudden cardiac death. Furthermore, coronary interventions performed in such high-risk patients have worse outcomes. In this narrative review, we discuss the role of diabetic dyslipidaemia on the risk of CHD in patients with T2DM. The effects of hypolipidaemic, antihypertensive and antidiabetic drugs on lipid and glucose metabolism in T2DM are also considered. Among CHD risk factors, diabetic dyslipidaemia characterized by moderately elevated low-density lipoprotein (LDL) cholesterol, increased triglycerides and small, dense LDL particles as well as decreased high-density lipoprotein cholesterol levels may contribute to the increased CHD risk associated with T2DM. Hypolipidaemic, antihypertensive and antidiabetic drugs can affect lipid and glucose parameters thus potentially influencing CHD risk. Such drugs may improve not only the quantity, but also the quality of LDL as well as postprandial lipaemia. Current data highlight the importance of treating diabetic dyslipidaemia in order to minimize CHD risk. Both fasting and postprandial lipids are influenced by drugs in patients with T2DM; physicians should take this into consideration in clinical decision making.

The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus

A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (n = 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m(2), HbA(1c) = 7.7 ± 0.3%) and normal glucose-tolerant (NGT) subjects (n = 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m(2), HbA(1c) = 5.6 ± 0.1%) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function [disposition index (DI)] was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine [TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin] values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8; p < 0.001). IS positively correlated with fasting plasma glucose (r = 0.638, p < 0.001), 1-h plasma glucose (r = 0.483, p = 0.005), 2-h plasma glucose (r = 0.611, p < 0.001) and HbA1c (r = 0.469, p = 0.007). IS was inversely correlated with insulin sensitivity (r = -0.478, p = 0.006) and DI (r = -0.523, p = 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (M/I < 4). A state of subclinical inflammation defined and quantifiable by inflammatory score including TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin is associated with both hyperglycemia and whole-body insulin resistance in T2DM.

The Relationship between Type 2 Diabetes Mellitus and Related Thyroid Diseases

Type 2 diabetes mellitus (T2DM) has an intersecting underlying pathology with thyroid dysfunction. The literature is punctuated with evidence indicating a contribution of abnormalities of thyroid hormones to type 2 DM. The most probable mechanism leading to T2DM in thyroid dysfunction could be attributed to perturbed genetic expression of a constellation of genes along with physiological aberrations leading to impaired glucose utilization and disposal in muscles, overproduction of hepatic glucose output, and enhanced absorption of splanchnic glucose. These factors contribute to insulin resistance. Insulin resistance is also associated with thyroid dysfunction. Hyper- and hypothyroidism have been associated with insulin resistance which has been reported to be the major cause of impaired glucose metabolism in T2DM. The state-of-art evidence suggests a pivotal role of insulin resistance in underlining the relation between T2DM and thyroid dysfunction. A plethora of preclinical, molecular, and clinical studies have evidenced an undeniable role of thyroid malfunctioning as a comorbid disorder of T2DM. It has been investigated that specifically designed thyroid hormone analogues can be looked upon as the potential therapeutic strategies to alleviate diabetes, obesity, and atherosclerosis. These molecules are in final stages of preclinical and clinical evaluation and may pave the way to unveil a distinct class of drugs to treat metabolic disorders.

A pilot study of the effects of pioglitazone and rosiglitazone on de novo lipogenesis in type 2 diabetes

Treatment of type 2 diabetes mellitus (T2DM) patients with pioglitazone results in a more favorable lipid profile, and perhaps more favorable cardiac outcomes, than treatment with rosiglitazone. Pioglitazone treatment increases VLDL-triacylglycerol clearance, but the role of de novo lipogenesis (DNL) has not been explored, and no direct comparison has been made between the thiazolidinediones (TZDs). Twelve subjects with T2DM and hypertriacylglyceridemia were randomized to either rosiglitazone or pioglitazone treatment. Stable isotope infusion studies were performed at baseline and after 20 weeks of treatment. Both treatments reduced glucose and HbA(1c) concentrations equally. Pioglitazone treatment resulted in a 40% reduction in hepatic DNL (P < 0.01) and in a 25% reduction in hepatic glucose production (P < 0.05), while rosiglitazone did not significantly change either parameter, although comparisons of changes between treatments were not significantly different. These pilot results indicate that pioglitazone reduces hepatic DNL while rosiglitazone does not. Larger follow-up studies are required to confirm differential effects of these agents definitively. The reduction in DNL may underlie altered assembly or atherogenicity of lipoprotein particles and may reflect PPARalpha or other non-PPARgamma actions on the liver by pioglitazone. These differences might help explain previously reported differences in lipid profiles and cardiovascular disease outcomes for rosiglitazone and pioglitazone.