Deficient leukemia inhibitory factor signaling in muscle precursor cells from patients with type 2 diabetes

The cytokine leukemia-inhibitory factor (LIF) is expressed by skeletal muscle and induces proliferation of muscle precursor cells, an important feature of skeletal muscle maintenance and repair. We hypothesized that muscle precursor cells from patients with type 2 diabetes had a deficient response to LIF. The mRNA and protein expressions of LIF and its receptor (LIFR) were measured in skeletal muscle biopsies from healthy individuals and patients with type 2 diabetes by use of qPCR and Western blot. LIF signaling and response were studied following administration of recombinant LIF and siRNA knockdown of suppressor of cytokine signaling (SOCS)3 in myoblast cultures established from healthy individuals and patients with type 2 diabetes. Myoblast proliferation rate was assessed by bromodeoxyuridine incorporation. LIF and LIFR proteins were increased in both muscle tissue and cultured myoblasts from diabetic patients. Nonetheless, in the diabetic myoblasts, LIF-induced phosphorylation of signal transducer and activator of transcription (STAT)1 and STAT3 was impaired. The deficient response to LIF administration in the diabetic myoblasts was further emphasized by a lack of increase in LIF-stimulated cell proliferation and a decreased LIF-stimulated induction of the proliferation-promoting factors cyclin D1, JunB, and c-myc. SOCS3 protein was upregulated in diabetic myoblasts, and knockdown of SOCS3 rescued LIF-induced gene expression in diabetic myoblasts, whereas neither STAT1 or STAT3 signaling nor proliferation rate was affected. In conclusion, although LIF and LIFR proteins were increased in muscle tissue and myoblasts from diabetic patients, LIF signaling and LIF-stimulated cell proliferation were impaired in diabetic myoblasts, suggesting a novel mechanism by which muscle function is compromised in diabetes.

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Dysregulated autophagy in muscle precursor cells from humans with type 2 diabetes

Scientific Reports ◽

10.1038/s41598-019-44535-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

T. I. Henriksen ◽

L. V. Wigge ◽

J. Nielsen ◽

B. K. Pedersen ◽

M. Sandri ◽

...

Keyword(s):

Type 2 Diabetes ◽

Precursor Cells ◽

Muscle Precursor ◽

Muscle Precursor Cells

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Elabela levels in patients with type 2 diabetes: can it be a marker for diabetic nephropathy?

African Health Sciences ◽

10.4314/ahs.v20i2.37 ◽

2020 ◽

Vol 20 (2) ◽

pp. 833-840

Author(s):

Erhan Onalan ◽

Yusuf Doğan ◽

Ebru Onalan ◽

Nevzat Gozel ◽

Ilay Buran ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Nephropathy ◽

High Serum ◽

Control Group ◽

Diabetic Patients ◽

Healthy Individuals ◽

Urine Albumin ◽

Healthy Control ◽

Group 2

Backround: Elabela (ELA) is a hormone that is secreted at high levels in the kidneys of a healthy adult. This study aims to investigate whether serum ELA levels of patients with Type 2 Diabetes vary with the severity of renal damage. Methods: Our study included 50 healthy control subjects and 100 diabetic patients, who were categorized into groups based on urine albumin/creatinine ratios (ACR). Patients included in the study were assigned to four groups: Group 1 (healthy control), Group 2 (ACR<29mg/g), Group 3 (ACR=30-299 mg/g), and Group 4 (ACR>300 mg/g normal or high serum creatinine). Physical examination findings, demographic characteristics of the study group were recorded, and serum ELA levels and other laboratory parameters were assessed using appropriate methods. Results: The results of the study indicated that ELA levels determined in healthy individuals gradually decreased through stages of normal albuminuria, microalbuminuria, and macroalbuminuria. Moreover, ELA had a significant negative corre- lation with LDL-C (r=-0.201, p=0.014), glucose (r=-0.437, P<0.001), retinopathy (r=-0.222, P=0.006), serum BUN (r=- 0.161, P=0.049), and a positive correlation with eGFR (r=0.250, P=0.002). Conclusions: The fact that ELA levels are higher in healthy individuals compared to diabetic patients without microalbu- minuria, and higher in diabetic patients without microalbuminuria compared to patients with advanced albuminuria and kidney damage, suggests that the ELA level can be an important clinical prognostic variable and even a promising agent for the treatment of diabetic nephropathy patients. Keywords: Elabela, diabetes, diabetic kidney disease, albuminuria.

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Intermuscular Fat Content in Young Chinese Men With Newly Diagnosed Type 2 Diabetes: Based on MR mDIXON-Quant Quantitative Technique

Frontiers in Endocrinology ◽

10.3389/fendo.2021.536018 ◽

2021 ◽

Vol 12 ◽

Author(s):

Fuyao Yu ◽

Bing He ◽

Li Chen ◽

Fengzhe Wang ◽

Haidong Zhu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Fat Content ◽

Control Group ◽

Diabetic Patients ◽

Diabetes Group ◽

Control Subjects ◽

Intermuscular Fat ◽

And Control

ObjectiveSkeletal muscle fat content is one of the important contributors to insulin resistance (IR), but its diagnostic value remains unknown, especially in the Chinese population. Therefore, we aimed to analyze differences in skeletal muscle fat content and various functional MRI parameters between diabetic patients and control subjects to evaluate the early indicators of diabetes. In addition, we aimed to investigate the associations among skeletal muscle fat content, magnetic resonance parameters of skeletal muscle function and IR in type 2 diabetic patients and control subjects.MethodsWe enrolled 12 patients (age:29-38 years, BMI: 25-28 kg/m2) who were newly diagnosed with type 2 diabetes (intravenous plasma glucose concentration≥11.1mmol/l or fasting blood glucose concentration≥7.0mmol/l) together with 12 control subjects as the control group (age: 26-33 years, BMI: 21-28 kg/m2). Fasting blood samples were collected for the measurement of glucose, insulin, 2-hour postprandial blood glucose (PBG2h), and glycated hemoglobin (HbAlc). The magnetic resonance scan of the lower extremity and abdomen was performed, which can evaluate visceral fat content as well as skeletal muscle metabolism and function through transverse relaxation times (T2), fraction anisotropy (FA) and apparent diffusion coefficient (ADC) values.ResultsWe found a significant difference in intermuscular fat (IMAT) between the diabetes group and the control group (p<0.05), the ratio of IMAT in thigh muscles of diabetes group was higher than that of control group. In the entire cohort, IMAT was positively correlated with HOMA-IR, HbAlc, T2, and FA, and the T2 value was correlated with HOMA-IR, PBG2h and HbAlc (p<0.05). There were also significant differences in T2 and FA values between the diabetes group and the control group (p<0.05). According to the ROC, assuming 8.85% of IMAT as the cutoff value, the sensitivity and specificity of IMAT were 100% and 83.3%, respectively. Assuming 39.25ms as the cutoff value, the sensitivity and specificity of T2 value were 66.7% and 91.7%, respectively. All the statistical analyses were adjusted for age, BMI and visceral fat content.ConclusionDeposition of IMAT in skeletal muscles seems to be an important determinant for IR in type 2 diabetes. The skeletal muscle IMAT value greater than 8.85% and the T2 value greater than 39.25ms are suggestive of IR.

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The Association of Food Insecurity, Inflammation, and Several Socioeconomic Factors with Type 2 Diabetes: A Case-Control Study

Journal of Nutrition and Food Security ◽

10.18502/jnfs.v5i1.2317 ◽

2020 ◽

Author(s):

Hamideh Janzadeh ◽

Hassan Mozaffari-Khosravi ◽

Maryam Javadi

Keyword(s):

Type 2 Diabetes ◽

Food Insecurity ◽

Case Control Study ◽

Economic Status ◽

Case Control ◽

Diabetic Patients ◽

Healthy Individuals ◽

Household Food ◽

Control Study

Background: Considering that food insecurity can be a precursor to health and nutrition problems, determining its associated factors seems necessary in any society. The purpose of this case-control study was to determine the food insecurity, c-reactive protein (CRP), and some socio-economic factors in type 2 diabetic patients. Methods: The present study was conducted on 200 people with type 2 diabetes mellitus (T2DM) and 200 healthy individuals within the age range of 30 to 59 years. Food security was assessed using the US Department of Agriculture Household Food Security questionnaire. Anthropometric index, physical activity, and biochemical factors were measured by questionnaire and blood test. Results: The prevalence of food insecurity was 71% within the diabetic patients, of which, 65.5% had food insecurity without hunger, 3.5% had food insecurity with moderate hunger, and 2% had food insecurity with severe hunger. In addition, 24.9% of the participants were healthy. The level of fasting blood glucose and inflammatory factors (CRP, WBC) were significantly higher in food insecure participants compared to the healthy individuals (P < 0.05). Multivariate logistic analysis showed that food insecurity, BMI > 25, occupational status, economic status, and education level were significantly correlated with T2DM (P < 0.001). Conclusion: As a result, health care providers should take measures to reduce the food insecurity in the community, specifically within T2DM patients. To this end, the individuals' economic status should be improved and the household food patterns should be modified.

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Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial?

Frontiers in Medicine ◽

10.3389/fmed.2021.712671 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dan Xu ◽

Owain Chandler ◽

Cleo Wee ◽

Chau Ho ◽

Jacquita S. Affandi ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Clinical Trial ◽

Diabetic Patients ◽

Atherosclerotic Cardiovascular Disease ◽

Healthy Individuals ◽

Type 2 Diabetic Patients ◽

Sodium Glucose Cotransporter ◽

Type 2 Diabetic

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a relatively novel class of drug for treating type 2 diabetes mellitus (T2DM) that inhibits glucose reabsorption in the renal proximal tubule to promote glycosuria and reduce blood glucose levels. SGLT2i has been clinically indicated for treating T2DM, with numerous recent publications focussing on both primary and secondary prevention of cardiovascular and renal events in Type 2 diabetic patients. The most recent clinical trials showed that SGLT2i have moderately significant beneficial effects on atherosclerotic major adverse cardiovascular events (MACE) in patients with histories of atherosclerotic cardiovascular disease. In this review and analysis, SGLT2i have however demonstrated clinically significant benefits in reducing hospitalisation for heart failure and worsening of chronic kidney disease (CKD) irrespective of pre-existing atherosclerotic cardiovascular disease or previous heart failure history. A meta-analysis suggests that all SGLT2 inhibitors demonstrated the therapeutic benefit on all-cause and cardiovascular mortality, as shown in EMPAREG OUTCOME study with a significant decrease in myocardial infarction, without increased stroke risk. All the above clinical trial recruited type 2 diabetic patients. This article aims to postulate and review the possible primary prevention role of SGLT2i in healthy individuals by reviewing the current literature and provide a prospective overview. The emphasis will include primary prevention of Type 2 Diabetes, Heart Failure, CKD, Hypertension, Obesity and Dyslipidaemia in healthy individuals, whom are defined as healthy, low or intermediate risks patients.

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Dipeptidyl-Peptidase-IV Inhibition Augments Postprandial Lipid Mobilization and Oxidation in Type 2 Diabetic Patients

Endocrinology ◽

10.1210/endo.150.2.9997 ◽

2009 ◽

Vol 150 (2) ◽

pp. 1069-1069

Author(s):

Michael Boschmann ◽

Stefan Engeli ◽

Kerstin Dobberstein ◽

Petra Budziarek ◽

Anke Strauss ◽

...

Keyword(s):

Type 2 Diabetes ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Standardized Test ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Diabetic Patients ◽

Lipid Mobilization ◽

Postprandial Lipid

Abstract Context: Dipeptidyl-peptidase-IV (DPP-4) inhibition increases endogenous GLP-1 activity resulting in improved glycemic control in patients with type 2 diabetes mellitus. The metabolic response may be explained in part by extra-pancreatic mechanisms. Objective: We tested the hypothesis that DPP-4 inhibition with vildagliptin elicits changes in adipose tissue and skeletal muscle metabolism. Design: Randomized, double blind, crossover study. Setting: Academic clinical research center. Patients: Twenty patients with type 2 diabetes, body mass index between 28 and 40 kg/m2. Intervention: Seven days treatment with the selective DPP-4 inhibitor vildagliptin or placebo. Standardized test meal on day seven. Main Outcome Measures: Venous DPP-4 activity, catecholamines, free fatty acids, glycerol, glucose, (pro)insulin; dialysate glucose, lactate, pyruvate, glycerol. Results: Fasting and postprandial venous insulin, glucose, glycerol, triglycerides and free fatty acid concentrations were not different with vildagliptin and with placebo. Vildagliptin augmented the postprandial increase in plasma norepinephrine. Furthermore, vildagliptine increased dialysate glycerol and lactate concentrations in adipose tissue while suppressing dialysate lactate and pyruvate concentration in skeletal muscle. The respiratory quotient increased with meal ingestion but was consistently lower with vildagliptin. Conclusions: Our study is the first to suggest that DPP-4 inhibition augments postprandial lipid mobilization and oxidation. The response may be explained by sympathetic activation rather than a direct effect on metabolic status.

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