Recovery Of Insulin Sensitivity Research Articles

JAB1 promotes palmitate-induced insulin resistance via ERK pathway in hepatocytes.

Insulin resistance (IR) is the primary pathological mechanism underlying Type 2 diabetes mellitus (T2DM). Many researches have reported the relationship between chronic inflammation and IR, while the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway is rapidly activated in inflammatory conditions. However, the functional role of ERK1/2 in IR remains to be identified. We here reported that C-Jun activation domain-binding protein-1 (JAB1) was upregulated in IR. In addition, we showed that depletion of JAB1 led to recovery of insulin sensitivity. Given the fact that JAB1 played as an activator of ERK1/2, we assumed JAB1 was involved in IR through ERK pathway. So we assessed the effects of JAB1 knockdown in palmitate acid (PA) treated HepG2 cells. Importantly, JAB1 siRNA blocked the effect of PA-induced activation of ERK1/2. Furthermore, silencing of JAB1 could reduce the release of inflammatory factors, facilitate hepatic glucose uptake and improve lipid metabolism. All these data implicated that JAB1 knockdown might alleviate PA-induced IR through ERK pathway in hepatocytes.

Lipidomic Changes in Skeletal Muscle in Patients after Biliopancreatic Diversion.

The mechanisms behind the fast improvements of insulin sensitivity and release of the diabetic metabolic state after bariatric surgery are still not completely understood. To further elucidate the effects on the individual cellular level, we applied mass spectrometry to investigate the changes in the lipidomic profile of skeletal muscle cells before and after biliopancreatic diversion in six patients. We found a decrease in lipid storage species, mainly triacylglycerides (e. g., TAG 52:2 from 19.84 to 13.26 mol%; p=0.028), and an increase in structural and signaling lipids, including phosphatidylcholines [PC 36:2 (18:1/18:1) from 0.12 to 0.65 mol%; p=0.046], phosphatidylinositols (PI 36:2 from 0.008 to 0.039 mol%; p=0.046), and cardiolipins (CL 72:8 from 0.16 to 1.22 mol%; p=0.043). The proportional increase in structural lipids was directly and the decrease in TAGs was inversely correlated to improved post-operative insulin sensitivity, measured by euglycemic hyperinsulinemic clamp. Thus, short-term recovery of insulin sensitivity after biliopancreatic diversion may, beside gut hormonal adaptation, mechanical factors, shifts in the gut microbiome, and changes in bile acid and phospholipid metabolism, additionally be attributed to a metabolic recovery of skeletal muscle cells, reflected by normalization of the cellular lipidomic profile. Further studies are needed to investigate whether improved insulin sensitivity of skeletal muscle might be directly associated with the degradation of ectopic triglycerides, thereby reducing the reservoir of lipotoxic intermediates, which might interfere with insulin signaling and hamper mitochondrial metabolism.

Recovery of insulin sensitivity and optimal body composition after rapid weight loss in obese dogs fed a high-protein medium-carbohydrate diet.

This study investigated the effects of an experimental high-protein medium-carbohydrate diet (protein level, 46% metabolizable energy, ME). First, postprandial plasma glucose and insulin kinetics were determined in steady-state overweight/obese Beagle dogs (28%-41% excess body weight) for an experimental high-protein medium-carbohydrate diet (protein level, 46% ME) and a commercial high-carbohydrate medium-protein diet (protein level, 24%ME) in obese dogs. Secondly, all the dogs were included in a weight loss programme. They were fed the high-protein medium-carbohydrate diet, and the energy allocation was gradually reduced until they reached their optimal body weight. Insulin sensitivity and body composition were evaluated before and after weight loss using a euglycaemic-hyperinsulinaemic clamp and the deuterium oxide dilution technique respectively. For statistical analysis, linear mixed effect models were used with a significance level of 5%. Postprandial plasma glucose and insulin concentrations were substantially lower with the high-protein medium-carbohydrate diet than the high-carbohydrate medium-protein diet. These differences can be explained mainly by the difference in carbohydrate content between the two diets. Energy restriction (35% lower energy intake than in the obese state) resulted in a 2.23±0.05% loss in body weight/week, and the dogs reached their optimal body weight in 12-16weeks. Weight loss was associated with a significant increase in insulin sensitivity. The high-protein medium-carbohydrate dietallowed fat-free mass preservation despite a relatively high rate of weekly weight loss. The increase in insulin sensitivity indicated improved control of carbohydrate metabolism, possible due to weight loss and to the nature of the diet. Thus, a high-protein medium-carbohydrate diet is a good nutritional solution for managing the weight of overweight dogs. This diet may improve glycaemic control, which could be beneficial for preventing or managing impaired glucose tolerance in obese dogs and for safe and successful weight loss while preserving lean body mass.

Recovery of insulin sensitivity in mature horses after a 3 week course of dexamethasone therapy

Dexamethasone is an anti-inflammatory drug commonly used in equine medicine. Insulin sensitivity decreases with prolonged dexamethasone administration, but little information is available about the duration of this side effect after long-term treatment ends. To determine how long it takes for blood glucose, insulin and markers of insulin sensitivity to return to normal ranges after extended dexamethasone treatment has ceased. Experimental study. Eight healthy, mature, mixed-breed horses received 0.04 mg/kg bwt/day oral dexamethasone for 21 days. Blood samples were taken weekly during dexamethasone treatment (Days -21, -14 and -7). Following the final dose of dexamethasone on Day 0, blood samples were taken on Days 1-6, 8, 10, 12, 15 and 22. Day -21 represents baseline or normal blood predexamethasone. On Day 1, plasma glucose and insulin concentrations and the modified insulin-to-glucose ratio (a proxy for pancreatic β cell responsiveness) were higher and the reciprocal of the square root of insulin (a proxy for the estimate of insulin sensitivity) was lower, in comparison with Day -21 values. Blood glucose concentrations dropped and returned to Day -21 values by Day 2. Insulin concentrations remained elevated until Day 3. Values for the modified insulin-to-glucose ratio decreased and returned to Day -21 concentrations by Day 4. Values for the reciprocal of the square root of insulin did not return to Day -21 values until Day 15. These results indicate that, in contrast to blood glucose concentrations, which return to normal quickly (within 2 days after treatment ends), the pancreatic insulin-secreting response has a delayed recovery.

ADV36 adipogenic adenovirus in human liver disease.

Obesity and liver steatosis are usually described as related diseases. Obesity is regarded as exclusive consequence of an imbalance between food intake and physical exercise, modulated by endocrine and genetic factors. Non-alcoholic fatty liver disease (NAFLD), is a condition whose natural history is related to, but not completely explained by over-nutrition, obesity and insulin resistance. There is evidence that environmental infections, and notably adipogenic adenoviruses (ADV) infections in humans, are associated not only with obesity, which is sufficiently established, but also with allied conditions, such as fatty liver. In order to elucidate the role, if any, of previous ADV36 infection in humans, we investigated association of ADV36-ADV37 seropositivity with obesity and fatty liver in humans. Moreover, the possibility that lifestyle-nutritional intervention in patients with NAFLD and different ADV36 seropositive status, achieves different clinical outcomes on ultrasound bright liver imaging, insulin resistance and obesity was challenged. ADV36 seropositive patients have a more consistent decrease in insulin resistance, fatty liver severity and body weight in comparison with ADV36 seronegative patients, indicating a greater responsiveness to nutritional intervention. These effects were not dependent on a greater pre-interventional body weight and older age. These results imply that no obvious disadvantage - and, seemingly, that some benefit - is linked to ADV36 seropositivity, at least in NAFLD. ADV36 previous infection can boost weight loss and recovery of insulin sensitivity under interventional treatment.

Recovery of insulin sensitivity and Slc2a4 mRNA expression depend on T3 hormone during refeeding

ObjectiveGLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression. Materials/MethodsPlasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4h after spontaneous refeeding; ii) 2–4h after T3 injection, without refeeding; and iii) 0.5–2h after intravenous infusion of insulin, insulin+glucose and insulin+amino acids, without refeeding. ResultsRefeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~20%, P<0.05 vs. fasting), but T3 injection induced a ~2-fold increase in Slc2a4 mRNA, 2–4h later (P<0.001). Moreover, T3 increased glycemia and insulinemia to the 2h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding. ConclusionsRefeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance.

Fast track surgery accelerates the postoperative rehabilitation and recovery of insulin sensitivity in elective operation for colorectal carcinoma: a randomized controlled clinical trial

To investigate the effects of fast track surgery on postoperative insulin sensitivity on the basis of clinical benefits in patients undergoing elective open colorectal resection. During May 2008 to December 2008, Seventy patients with colorectal carcinoma requiring colorectal resection were randomized into two groups: a fast track group (35 cases) and a conventional care group (35 cases). All included patients received elective open colorectal resection with combined tracheal intubation and general anesthesia. Clinical parameters, stress markers and insulin sensitivity were evaluated in both groups. The 62 patients finally completed the study, 32 cases in the fast-track group and 30 cases in the conventional care group. The speed of recovery of postoperative insulin sensitivity on 7 days postoperative in the fast-track group (97% ± 9%) was significantly faster than the conventional care group (88.5% ± 9.0%, t = 2.552, P = 0.016). The hospitalization days in the fast-track group was 6 days (M(50)), and it was significantly shorter than the conventional care group ((11.7 ± 3.8) days, Z = 4.360, P = 0.000). The time of recovery of bowel function were faster in the fast-track group (time to pass flatus was 2 days (M(50))) than the conventional care group (4 days, Z = 3.976, P = 0.000). The Infectious complication rate in the fast-track group (2/32) is lower than the other group (8/30, P = 0.040). Fast track surgery accelerates recovery of postoperative insulin sensitivity in elective surgery for colorectal carcinoma with a lower rate of postoperative infectious complications and a shorter length of postoperative hospital stay.

Adenovirus-36 Seropositivity Enhances Effects of Nutritional Intervention on Obesity, Bright Liver, and Insulin Resistance

Obesity and liver steatosis are both currently attributed to inappropriate lifestyle and nutrition. Higher prevalence of human adenovirus Ad36 seropositivity (Ad36+) is reported only in obesity. To investigate whether a lifestyle-nutritional intervention achieves different outcomes in NAFLD patients, i.e., if is blunted or enhanced according to Ad36 seropositivity status. One-year nutritional intervention was planned and accomplished for 62 non-alcoholic fatty liver disease overweight-obese patients, studied by liver ultrasound, evaluating Bright Liver Score (BLS), by Homeostatic Model assessment of Insulin Resistance (HOMA), by body composition and Ad36+ assay. Lower salt/lower calories Mediterranean diet, physical activity increase, smoking withdrawal and lifestyle counseling, provided by a health psychologist, were given. Ad36 seropositive patients have baseline greater BMI with the same level of BLS. Different prevalence of post-interventional response, significantly greater among Ad36+ patients, is observed: greater decrease of obesity, assessed by BMI, greater reduction of insulin resistance, assessed by HOMA and higher prevalence of bright liver disappearance. A BMI-adjusted multiple linear regression model explains significantly 23.8% (p < 0.04) of the variance; significant predictive variables are Ad36 seropositivity (p < 0.012) and fat mass loss (p < 0.011) accounting for the variance of the occurrence of bright liver disappearance. Ad36 previous infection is significantly associated with enhanced weight loss, bright liver disappearance, and recovery of insulin sensitivity through the chosen tailored nutritional interventional treatment. Nonetheless, Ad36 seronegative NAFLD patients' fatty liver pattern improves, at a lower extent, also without significant weight loss: an effect of dietary changes profile, Mediterranean diet, not only of lowered food caloric intake, is conceivably operating.

Insulin Resistance Affects Early Virologic Response in HIV-Infected Subjects Treated for Hepatitis C Infection

Insulin Resistance Affects Early Virologic Response in HIV-Infected Subjects Treated for Hepatitis C Infection

Adenosine Triphosphate-dependent Inhibition of Insulin-stimulated Glucose Transport in Fat Cells: POSSIBLE ROLE OF MEMBRANE PHOSPHORYLATION

Abstract Addition of low concentrations of ATP, but not other nucleoside triphosphates, to fat cells inhibits insulin-stimulated glucose oxidation under conditions that measure glucose transport. Basal rates of glucose transport are not inhibited. The inhibition cannot be overcome by increasing the concentration of insulin, and the dose-response relationships indicate no gross alteration in the apparent affinity of the cells for the hormone. The binding of 125I-labeled insulin is not altered by ATP. Under the conditions used, ATP does not alter oxidation by affecting cytoplasmic metabolic processes. The effects of exogenous ATP on glucose transport were confirmed by direct measurements of 3H-labeled 3-O-methyl-d-glucose uptake in isolated fat cells. ATP inhibits the insulin-stimulated but not the basal rate of 3-O-methylglucose transport. The inhibition by ATP is relatively selective since it represents a fall in the apparent affinity for glucose of the insulin-activated component of the glucose transport system. The inhibition can be overcome by high glucose concentrations. The antilipolytic activity of insulin in ATP-treated cells is unaffected while insulin-stimulated transport is markedly depressed; these activities of insulin can thus be dissociated. ATP also inhibits the enhanced rates of glucose transport observed with concanavalin A, wheat germ agglutinin, spermine, spermidine, cysteine, and glutathione, substances that activate the same glucose transport system as insulin. The ouabain-stimulated glucose oxidation, which occurs by mechanisms different from those of insulin, is not affected by ATP. The ATP analog, α,β-methylene-adenosine 5'-triphosphate (Ap(CH2)pp), can mimic the effect of ATP. Another analog, β,γ-methylene-adenosine 5'-triphosphate (App(CH2)p), does not suppress insulin-stimulated transport but it can effectively inhibit the ATP effect; this phosphonic acid analog cannot donate its terminal phosphoryl moiety in phosphorylation reactions. Phloretin, a strong competitive inhibitor of d-glucose transport, can protect the cells from the ATP effect. Phlorizin, another competitive inhibitor, potentiates the effect of ATP. Fat cells exposed to low concentrations (5 to 50 µm) of ATP for a short time (5 min) at 24° continue to exhibit a diminished insulin response (glucose transport) after thorough washing to remove the ATP in the medium. The recovery of insulin sensitivity during subsequent incubation at 37° is slow, pointing to the protracted and relatively irreversible effect of such mild treatment with ATP. Brief treatment of cells with [γ-32P]ATP results in the selective phosphorylation of two plasma membrane components which are estimated to be of molecular weight 16,000 and 22,000 by sodium dodecyl sulfate gel electrophoresis. Phosphorylation of the latter is inhibited by phloretin, and phosphorylation of both is inhibited by App(CH2)p. The possibility is entertained that the procedures utilized may selectively label membrane components involved in insulin-mediated glucose transport (glucose carriers). Consideration is given to the possible physiological significance of such selective membrane phosphorylation in the control of insulin sensitivity in normal as well as insulin-resistant states.