דו״ח מאומת

Most human cells utilize glucose as the primary substrate, cellular uptake requiring insulin. Insulin signaling is therefore critical for these tissues. However, decrease in insulin sensitivity due to the disruption of various molecular pathways causes insulin resistance (IR). IR underpins many metabolic disorders such as type 2 diabetes and metabolic syndrome, impairments in insulin signaling disrupting entry of glucose into the adipocytes, and skeletal muscle cells. Although the exact underlying cause of IR has not been fully elucidated, a number of major mechanisms, including oxidative stress, inflammation, insulin receptor mutations, endoplasmic reticulum stress, and mitochondrial dysfunction have been suggested. In this review, we consider the role these cellular mechanisms play in the development of IR.…

PMID: 30317615

The skeletal muscle is the largest organ in the body, by mass. It is also the regulator of glucose homeostasis, responsible for 80% of postprandial glucose uptake from the circulation. Skeletal muscle is essential for metabolism, both for its role in glucose uptake and its importance in exercise and metabolic disease. In this article, we give an overview of the importance of skeletal muscle in metabolism, describing its role in glucose uptake and the diseases that are associated with skeletal muscle metabolic dysregulation. We focus on the role of skeletal muscle in peripheral insulin resistance and the potential for skeletal muscle-targeted therapeutics to combat insulin resistance and diabetes, as well as other metabolic diseases like aging and obesity. In particular, we outline the possibilities and pitfalls of the quest for exercise mimetics, which are intended to target the molecular mechanisms underlying the beneficial effects of exercise on metabolic disease. We also provide a description of the molecular mechanisms that regulate skeletal muscle glucose uptake, including a focus on the SNARE proteins, which are essential regulators of glucose transport into the skeletal muscle. © 2020 American Physiological Society. Compr Physiol 10:785-809, 2020.…

PMID: 32940941

Skeletal muscle is essential for movement and maintaining energy homeostasis and is the primary tissue for insulin-stimulated glucose uptake. Skeletal muscle is composed of various cell types that help to govern the delivery, transport, and metabolism of nutrients to and within the tissue. Dysregulation of these processes can result in impaired insulin-stimulated glucose uptake and dysglycemia-insulin resistance and type 2 diabetes. Acute exercise and chronic exercise training provide a robust stimulus to improve nutrient delivery, nutrient transport into a cell, and subsequent storage and oxidation to help improve insulin sensitivity. This review details the molecular mechanisms of skeletal muscle insulin resistance and how exercise counteracts these defects, highlighting the key role of exercise in muscle health and disease.…

PMID: 40608853

Muscle insulin resistance is characterized by the inability of a normal insulin concentration to produce a favorable rate of glucose uptake. The muscle of the obese Zucker rat is highly insulin resistant. The purpose of this review is to discuss the cellular defects associated with the muscle insulin resistance of the obese Zucker rat, as well as the mechanisms by which exercise training alleviates or compensates for these defects. Emphasis will be given to the importance of an increased GLUT4 expression on alleviating muscle insulin resistance. A review of the relative research from my laboratory and the scientific literature was performed to obtain information on the muscle insulin resistance of the obese Zucker rat and its response to exercise training. The insulin resistance of the obese Zucker rat results from defects in the insulin signaling cascade, which limits translocation of the glucose transporter GLUT4 to the plasma membrane upon insulin binding to its receptor. Exercise training improves the muscle insulin resistance of obese Zucker rat but does not correct the defects in insulin signaling or GLUT4 translocation. The improvement in insulin resistance, i.e., glucose transport, is correlated with an increased expression of GLUT4 protein. Preventing GLUT4 overexpression during exercise training will inhibit the improvement in insulin-stimulated glucose transport. Exercise training does not correct but compensates for the defects in muscle insulin resistance by increasing expression of GLUT4. This increase in GLUT4 protein is essential for the improvement in muscle insulin resistance.…

PMID: 15235327

Physical exercise can be an important adjunct in the treatment of both non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non-insulin-dependent diabetes mellitus.…

PMID: 9509261

This study aimed to compare the effect of different physical training on the mechanism of ceramidedependent insulin resistance in the flexor hallucis longus (FHL) muscle of diabetic rats. In this experimental study, 7 healthy as a healthy control (HC) group, and 21 diabetics (55 mg/ kg Streptozotocin) Wistar rats (200-220 g; 8-10 weeks old) divided into the diabetic control (DC), moderate continuous training (MCT), and moderate intensity interval training (MIIT) groups. Both MCT (55-70% of maximal oxygen uptake (VO Blood glucose, triglyceride (TG) and ceramide synthase-1 (CS1) expression levels in the MCT group decreased in comparison with the DC group. FHL protein expression of GLUT4 in the MCT group was higher than the DC group. FHL expression of GLUT4, pAKT, AKT/pAKT, PKC, CS1 and total ceramide in the MIIT group were higher than the DC group. Cholesterol, low-density lipoprotein (LDL), TG, and TNF-α protein expression in the MIIT group were lower than the DC group. GLUT4, PKC, pAKT, AKT/pAKT in the MIIT group were higher, and total ceramide and TNF-α were lower in the MIIT group than the MCT group. It seems that both training plan MIIT and MCT have favorable effects on the metabolism of glucose, insulin, lipids, and the decrease of TNFα level in the diabetes, but in connection with the improvement of the ceramides mechanism, it seems that the MIIT training plan is more optimal than MCT training plan.…

PMID: 37543859

Physical exercise can be an important adjunct in the treatment of both non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus. Over the past several years, considerable progress has been made in understanding the molecular basis for these clinically important effects of physical exercise. Similarly to insulin, a single bout of exercise increases the rate of glucose uptake into the contracting skeletal muscles, a process that is regulated by the translocation of GLUT4 glucose transporters to the plasma membrane and transverse tubules. Exercise and insulin utilize different signaling pathways, both of which lead to the activation of glucose transport, which perhaps explains why humans with insulin resistance can increase muscle glucose transport in response to an acute bout of exercise. Exercise training in humans results in numerous beneficial adaptations in skeletal muscles, including an increase in GLUT4 expression. The increase in muscle GLUT4 in trained individuals contributes to an increase in the responsiveness of muscle glucose uptake to insulin, although not all studies show that exercise training in patients with diabetes improves overall glucose control. However, there is now extensive epidemiological evidence demonstrating that long-term regular physical exercise can significantly reduce the risk of developing non-insulin-dependent diabetes mellitus.…

PMID: 9509261

(1) Background: The increased risk of developing hypoglycemia and worsening of glycemic stability during exercise is a major cause of concern for patients with type 1 diabetes mellitus (T1DM). (2) Aim: This pilot study aimed to assess glycemic stability and hypoglycemic episodes during and after aerobic versus resistance exercises using a flash glucose monitoring system in patients with T1DM. (3) Participants and Methods: We conducted a randomized crossover prospective study including 14 adult patients with T1DM. Patients were randomized according to the type of exercise (aerobic vs. resistance) with a recovery period of three days between a change of groups. Glucose stability and hypoglycemic episodes were evaluated during and 24 h after the exercise. Growth hormone (GH), cortisol, and lactate levels were determined at rest, 0, 30, and 60 min post-exercise period. (4) Results: The median age of patients was 53 years, with a median HbA1c of 7.1% and a duration of diabetes of 30 years. During both training sessions, there was a drop in glucose levels immediately after the exercise (0'), followed by an increase at 30' and 60', although the difference was not statistically significant. However, glucose levels significantly decreased from 60' to 24 h in the post-exercise period (…

PMID: 36981876

There is a need for updated practice recommendations on exercise in the management of overweight and obesity in adults. We summarize the evidence provided by a series of seven systematic literature reviews performed by a group of experts from across Europe. The following recommendations with highest strength (Grade A) were derived. For loss in body weight, total fat, visceral fat, intra-hepatic fat, and for improvement in blood pressure, an exercise training program based on aerobic exercise at moderate intensity is preferentially advised. Expected weight loss is however on average not more than 2 to 3 kg. For preservation of lean mass during weight loss, an exercise training program based on resistance training at moderate-to-high intensity is advised. For improvement in insulin sensitivity and for increasing cardiorespiratory fitness, any type of exercise training (aerobic, resistance, and combined aerobic or resistance) or high-intensity interval training (after thorough assessment of cardiovascular risk and under supervision) can be advised. For increasing muscular fitness, an exercise training program based preferentially on resistance training alone or combined with aerobic training is advised. Other recommendations deal with the beneficial effects of exercise training programs on energy intake and appetite control, bariatric surgery outcomes, and quality of life and psychological outcomes in management of overweight and obesity.…

PMID: 34076949

An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [(18)F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) μmol·kg body wt(-1)·min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt(-1)·min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training.…

PMID: 26744506

Age-dependent changes in insulin action and body fat distribution are risk factors for the development of type 2 diabetes. To examine whether the accumulation of visceral fat (VF) could play a direct role in the pathophysiology of insulin resistance and type 2 diabetes, we monitored insulin action, glucose tolerance, and the expression of adipo-derived peptides after surgical removal of VF in aging (20-month-old) F344/Brown Norway (FBN) and in Zucker Diabetic Fatty (ZDF) rats. As expected, peripheral and hepatic insulin action were markedly impaired in aging FBN rats, and extraction of VF (accounting for approximately 18% of their total body fat) was sufficient to restore peripheral and hepatic insulin action to the levels of young rats. When examined at the mechanistic level, removal of VF in ZDF rats prevented the progressive decrease in insulin action and delayed the onset of diabetes, but VF extraction did not alter plasma free fatty acid levels. However, the expression of tumor necrosis factor-alpha and leptin in subcutaneous (SC) adipose tissue were markedly decreased after VF removal (by approximately three- and twofold, respectively). Finally, extracted VF retained approximately 15-fold higher resistin mRNA compared with SC fat. Our data suggest that insulin resistance and the development of diabetes can be significantly reduced in aging rats by preventing the age-dependent accumulation of VF. This study documents a cause-and-effect relationship between VF and major components of the metabolic syndrome.…

PMID: 12351432