Reduced insulin-stimulated glucose transport in denervated muscle is associated with impaired Akt-α activation

2000 ◽  
Vol 279 (4) ◽  
pp. E912-E919 ◽  
Author(s):  
Jason J. Wilkes ◽  
Arend Bonen

Insulin signaling was examined in muscle made insulin resistant by short-term (24-h) denervation. Insulin-stimulated glucose transport in vitro was reduced by 28% ( P < 0.05) in denervated muscle (DEN). In control muscle (SHAM), insulin increased levels of surface-detectable GLUT-4 (i.e., translocated GLUT-4) 1.8-fold ( P < 0.05), whereas DEN surface GLUT-4 was not increased by insulin ( P > 0.05). Insulin treatment in vivo induced a rapid appearance of phospho[Ser473]Akt-α in SHAM 3 min after insulin injection. In DEN, phospho[Ser473]Akt-α also appeared at 3 min, but Ser473-phosphorylated Akt-α was 36% lower than in SHAM ( P < 0.05). In addition, total Akt-α protein in DEN was 37% lower than in SHAM ( P < 0.05). Akt-α kinase activity was lower in DEN at two insulin levels tested: 0.1 U insulin/rat (−22%, P < 0.05) and 1 U insulin/rat (−26%, P < 0.01). These data indicate that short-term (24-h) denervation, which lowers insulin-stimulated glucose transport, is associated with decreased Akt-α activation and impaired insulin-stimulated GLUT-4 appearance at the muscle surface.

1991 ◽  
Vol 260 (3) ◽  
pp. E459-E463 ◽  
Author(s):  
G. L. Dohm ◽  
C. W. Elton ◽  
J. E. Friedman ◽  
P. F. Pilch ◽  
W. J. Pories ◽  
...  

We have observed that in vitro incubated human muscle fiber strips from obese patients with or without non-insulin-dependent diabetes mellitus (NIDDM) have reduced insulin-stimulated glucose transport rates compared with nonobese control patients. To investigate if the decrease in glucose transport is associated with a depletion of glucose transport protein, we performed Western blot analysis of muscle samples from nonobese control, obese nondiabetic, and obese NIDDM patients to measure the levels of the muscle-adipose tissue glucose transporter (GLUT-4) protein. Glucose transporter protein was depressed by 23% in the obese nondiabetic and 18% in the obese NIDDM group. The results were essentially the same in the rectus abdominus and vastus lateralis muscles. These data suggest that the decreased glucose transport rate observed in muscle of these obese patients with or without NIDDM may be due, at least in part, to a decreased expression of the "insulin-sensitive" (GLUT-4) glucose transporter. This alteration may play a role in the insulin resistance seen in obesity and diabetes.


Author(s):  
Daniel L. Villeneuve ◽  
Brett R. Blackwell ◽  
Jenna E. Cavallin ◽  
Wan‐Yun Cheng ◽  
David J. Feifarek ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 987
Author(s):  
Eric J. O’Neill ◽  
Deborah Termini ◽  
Alexandria Albano ◽  
Evangelia Tsiani

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.


1969 ◽  
Vol 49 (2) ◽  
pp. 135-141 ◽  
Author(s):  
L. P. Milligan ◽  
A. R. Robblee ◽  
J. C. Wood ◽  
W. C. Kay ◽  
S. K. Chakrabartty

The preparation of a polymer of urea and furfural containing 23.2% nitrogen is described. This product was converted by rumen microorganisms in vitro to ammonia at a rate approximately one-seventh that of conversion of urea to ammonia. Use of the polymer as a dietary supplement in a feeding trial with lambs improved nitrogen retention over that of unsupplemented controls by 3.45 g of nitrogen retained per day, while an isonitrogenous quantity of supplemental urea improved nitrogen retention by 0.51 g of nitrogen retained per day. The blood urea pattern, throughout the day, of lambs adapted to control, urea-supplemented and urea–furfural polymer-supplemented rations indicated a slow, prolonged production of ammonia from the latter supplement and very rapid, short-term degradation of urea in vivo.


Development ◽  
1966 ◽  
Vol 15 (2) ◽  
pp. 133-141
Author(s):  
T. N. Chapekar ◽  
G. V. Nayak ◽  
Kamal J. Ranadive

Short-term maintenance of mouse and rat ovary in organotypic culture system is no longer a problem (Martinovitch, 1938; Gaillard, 1953; Trowell, 1959). Gaillard (1953) cultivated ovaries from 7- to 8-day-old and 21-day-old mice for a week on the plasma clot. Trowell (1959) maintained ovaries of 8-day-old mice on a synthetic medium in an O2-CO2 atmosphere for 9 days. He observed no histological differentiation in the tissues of the ovary. What needs confirmation and further investigation is the possibility of maintenance of functional activity of the ovary under culture conditions. A study was therefore undertaken to investigate if an ovary, cultivated in vitro for some time, shows hormonal activity when transplanted in vivo. In the present work cultured ovaries were grafted in the anterior eye-chamber of spayed female mice and the development of secondary sex organs such as mammary glands and uterus was studied.


2014 ◽  
Vol 50 (2) ◽  
pp. 251-256
Author(s):  
Igor Vivian de Almeida ◽  
Giovana Domingues ◽  
Lilian Capelari Soares ◽  
Elisângela Düsman ◽  
Veronica Elisa Pimenta Vicentini

Flunitrazepam (FNZ) is a sedative benzodiazepine prescribed for the short-term treatment of insomnia. However, there are concerns regarding possible carcinogenic or genotoxic effects of this medicine. Thus, the aim of this study was to evaluate the cytotoxic, clastogenic and aneugenic effects of FNZ in hepatoma cells from Rattus norvegicus (HTC) in vitro and in bone marrow cells of Wistar rats in vivo. These effects were examined in vitro following treatment with 0.2, 1.0, 5.0 or 10 μg/mL FNZ using a micronucleus test with a cytokinesis block or in vivo using a chromosomal aberration test following treatment with 7, 15 or 30 μg/mL/kg body weight. The results showed that the benzodiazepine concentrations tested were not cytotoxic, aneugenic or clastogenic. However, considering the adverse effects of using this benzodiazepine, more studies are required.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Cheng-Chih Tsai ◽  
Sew-Fen Leu ◽  
Quan-Rong Huang ◽  
Lan-Chun Chou ◽  
Chun-Chih Huang

Three lactic acid bacterial strains,Lactobacillus plantarum, HK006, and HK109, andPediococcus pentosaceusPP31 exhibit probiotic potential as antiallergy agents, both in vitro and in vivo. However, the safety of these new strains requires evaluation when isolated from infant faeces or pickled cabbage. Multiple strains (HK006, HK109, and PP31) were subject to a bacterial reverse mutation assay and a short-term oral toxicity study. The powder product exhibited mutagenic potential inSalmonellaTyphimurium strains TA98 and TA1535 (with or without metabolic activation). In the short-term oral toxicity study, rats received a normal dosage of 390 mg/kg/d (approximately9×109 CFU/kg/d) or a high dosage of 1950 mg/kg/d (approximately4.5×1010 CFU/kg/d) for 28 d. No adverse effects were observed regarding the general condition, behaviour, growth, feed and water consumption, haematology, clinical chemistry indices, organ weights, or histopathologic analysis of the rats. These studies have demonstrated that the consumption of multiple bacterial strains is not associated with any signs of mutagenicity ofS.Typhimurium or toxicity in Wistar rats, even after consuming large quantities of bacteria.


1998 ◽  
Vol 85 (6) ◽  
pp. 2106-2111 ◽  
Author(s):  
Cynthia M. Ferrara ◽  
Thomas H. Reynolds ◽  
Mary Jane Zarnowski ◽  
Joseph T. Brozinick ◽  
Samuel W. Cushman

This investigation examined the effects of short-term exercise training on insulin-stimulated GLUT-4 glucose transporter translocation and glucose transport activity in rat adipose cells. Male Wistar rats were randomly assigned to a sedentary (Sed) or swim training group (Sw, 4 days; final 3 days: 2 × 3 h/day). Adipose cell size decreased significantly but minimally (∼20%), whereas total GLUT-4 increased by 30% in Sw vs. Sed rats. Basal 3- O-methyl-d-[14C]glucose transport was reduced by 62%, whereas maximally insulin-stimulated (MIS) glucose transport was increased by 36% in Sw vs. Sed rats. MIS cell surface GLUT-4 photolabeling was 44% higher in the Sw vs. Sed animals, similar to the increases observed in MIS glucose transport activity and total GLUT-4. These results suggest that increases in total GLUT-4 and GLUT-4 translocation to the cell surface contribute to the increase in MIS glucose transport with short-term exercise training. In addition, the results suggest that the exercise training-induced adaptations in glucose transport occur more rapidly than previously thought and with minimal changes in adipose cell size.


2009 ◽  
Vol 160 (5) ◽  
pp. 785-790 ◽  
Author(s):  
Eirini Maratou ◽  
Dimitrios J Hadjidakis ◽  
Anastasios Kollias ◽  
Katerina Tsegka ◽  
Melpomeni Peppa ◽  
...  

ObjectiveAlthough clinical hypothyroidism (HO) is associated with insulin resistance, there is no information on insulin action in subclinical hypothyroidism (SHO).Design and methodsTo investigate this, we assessed the sensitivity of glucose metabolism to insulin both in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes with flow cytometry) in 21 euthyroid subjects (EU), 12 patients with HO, and 13 patients with SHO.ResultsAll three groups had comparable plasma glucose levels, with the HO and SHO having higher plasma insulin than the EU (P<0.05). Homeostasis model assessment index was increased in HO (1.97±0.22) and SHO (1.99±0.13) versus EU (1.27±0.16, P<0.05), while Matsuda index was decreased in HO (3.89±0.36) and SHO (4.26±0.48) versus EU (7.76±0.87, P<0.001), suggesting insulin resistance in both fasting and post-glucose state. At 100 μU/ml insulin: i) GLUT4 levels on the monocyte plasma membrane were decreased in both HO (215±19 mean fluorescence intensity, MFI) and SHO (218±24 MFI) versus EU (270±25 MFI, P=0.03 and 0.04 respectively), and ii) glucose transport rates in monocytes from HO (481±30 MFI) and SHO (462±19 MFI) were decreased versus EU (571±15 MFI, P=0.04 and 0.004 respectively).ConclusionsIn patients with HO and SHO: i) insulin resistance was comparable; ii) insulin-stimulated rates of glucose transport in isolated monocytes were decreased due to impaired translocation of GLUT4 glucose transporters on the plasma membrane; iii) these findings could justify the increased risk for insulin resistance-associated disorders, such as cardiovascular disease, observed in patients with HO or SHO.


Sign in / Sign up

Export Citation Format

Share Document