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 Basic disturbances in skeletal muscle fatty acid metabolism in obesity and type 2 diabetes mellitus

2004 ◽  
Vol 63 (2) ◽  
pp. 323-330 ◽  
Author(s):  
E. E. Blaak
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Fatty Acid ◽  
Fat Oxidation ◽  
Adrenergic Stimulation ◽  
Skeletal Muscle Insulin Resistance

The present article addresses the hypothesis that disturbances in skeletal muscle fatty acid handling in abdominal obesity and type 2 diabetes mellitus may play a role in the aetiology of increased adipose tissue stores, increased triacylglycerol storage in skeletal muscle and skeletal muscle insulin resistance. The uptake and/or oxidation of fatty acids have been shown to be impaired during post-absorptive conditions in abdominally-obese subjects and/or subjects with type 2 diabetes. Also, human studies have shown that muscle of subjects that are (abdominally) obese and/or have type 2 diabetes is characterized by an inability to increase fatty acid uptake and/or fatty acid oxidation during β-adrenergic stimulation and exercise. This disturbance in fat oxidation may promote, on one hand, the development of increased adipose tissue stores and obesity. On the other hand, fatty acids that are taken up by muscle and not oxidized may increase triacylglycerol storage in muscle, which has been associated with skeletal-muscle insulin resistance. Disturbances in the capacity to increase fat oxidation during post-absorptive conditions, β-adrenergic stimulation and exercise in subjects who are obese and/or have type 2 diabetes persist after weight reduction, indicating that the diminished fat oxidation may be a primary factor leading to the obese and/or insulin-resistant state rather than an adaptational response. Clearly, the precise sequence of events leading to an increased adiposity and insulin resistance in obesity and type 2 diabetes mellitus is not yet fully understood.

Serum Myostatin is Upregulated in Obesity and Correlates with Insulin Resistance in Humans

2018 ◽  
Vol 127 (08) ◽  
pp. 550-556 ◽  
Author(s):  
Melina Amor ◽  
Bianca K. Itariu ◽  
Veronica Moreno-Viedma ◽  
Magdalena Keindl ◽  
Alexander Jürets ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Obese Group ◽  
Sensitivity Indices

AbstractObesity and type 2 diabetes mellitus have reached an epidemic level, thus novel treatment concepts need to be identified. Myostatin, a myokine known for restraining skeletal muscle growth, has been associated with the development of insulin resistance and type 2 diabetes mellitus. Yet, little is known about the regulation of myostatin in human obesity and insulin resistance. We aimed to investigate the regulation of myostatin in obesity and uncover potential associations between myostatin, metabolic markers and insulin resistance/sensitivity indices. Circulating active myostatin concentration was measured in the serum of twenty-eight severely obese non-diabetic patients compared to a sex and age matched lean and overweight control group (n=22). Insulin resistance/sensitivity was assessed in the obese group. Skeletal muscle and adipose tissue specimens from the obese group were collected during elective bariatric surgery. Adipose tissue samples from lean and overweight subjects were collected during elective abdominal surgery. Myostatin concentration was increased in obese compared to lean individuals, while myostatin adipose tissue expression did not differ. Muscle myostatin gene expression strongly correlated with expression of metabolic genes such as IRS1, PGC1α, SREBF1. Circulating myostatin concentration correlated positively with insulin resistance indices and negatively with insulin sensitivity indices. The best correlation was obtained for the oral glucose insulin sensitivity index. Our results point to an interesting correlation between myostatin and insulin resistance/sensitivity in humans, and emphasize its need for further evaluation as a pharmacological target in the prevention and treatment of obesity-associated metabolic complications.

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 Changes in microvascular density differentiate metabolic health outcomes in monkeys with prior radiation exposure and subsequent skeletal muscle ECM remodeling

2017 ◽  
Vol 313 (3) ◽  
pp. R290-R297 ◽  
Author(s):  
K. M. Fanning ◽  
B. Pfisterer ◽  
A. T. Davis ◽  
T. D. Presley ◽  
I. M. Williams ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Radiation Exposure ◽  
Microvascular Density ◽  
Whole Body ◽  
Ecm Remodeling

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5–9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques ( Macaca mulatta, n = 7–8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-β1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.

scholarly journals Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background: Globally, 1 in 11 adults have diabetes mellitus and 90% of the cases are type 2 diabetes mellitus. Asia is the epicenter of this global type 2 diabetes mellitus epidemic. Type 2 diabetes mellitus and its complications have contributed significantly to the burden of mortality and disability worldwide. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus more effective methods are required to improve insulin resistance. Methods: In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection and skeletal muscle injection. Body weight, fasting blood glucose and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results: The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation; regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions: These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

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 Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Guang Chen ◽  
Xiao-yan Fan ◽  
Xiao-peng Zheng ◽  
Yue-lei Jin ◽  
Ying Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Stem Cells ◽  
Type 2 Diabetes Mellitus ◽  
Human Umbilical Cord ◽  
Tail Vein Injection ◽  
Ameliorate Insulin Resistance

Abstract Background Globally, 1 in 11 adults have diabetes mellitus, and 90% of the cases are type 2 diabetes mellitus. Insulin resistance is a central defect in type 2 diabetes mellitus, and although multiple drugs have been developed to ameliorate insulin resistance, the limitations and accompanying side effects cannot be ignored. Thus, more effective methods are required to improve insulin resistance. Methods In the current study, db/m and db/db mice were injected with human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) via tail vein injection, intraperitoneal injection, and skeletal muscle injection. Body weight, fasting blood glucose, and the survival rates were monitored. Furthermore, the anti-insulin resistance effects and potential mechanisms of transplanted HUC-MSCs were investigated in db/db mice in vivo. Results The results showed that HUC-MSC transplantation by skeletal muscle injection was safer compared with tail vein injection and intraperitoneal injection, and the survival rate reached 100% in the skeletal muscle injection transplanted mice. HUC-MSCs can stabilize localization and differentiation in skeletal muscle tissue and significantly ameliorate insulin resistance. Potential regulatory mechanisms are associated with downregulation of inflammation, regulating the balance between PI3K/Akt and ERK/MAPK signaling pathway via PTEN, but was not associated with the IGF-1/IGF-1R signaling pathway. Conclusions These results suggest HUC-MSC transplantation may be a novel therapeutic direction to prevent insulin resistance and increase insulin sensitivity, and skeletal muscle injection was the safest and most effective way.

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