Reported discrepancies in the effects of tumor necrosis factor (TNF)-␣ in modulating insulin sensitivity of cultured cells may relate both to cell types studied and to the time course of exposure to the cytokine. Additionally, the relationship of effects on glucose metabolism to changes in the insulin signaling pathway cannot be assumed. For in vitro study, the cell type most relevant to insulin resistance in humans is the cultured human muscle cell. In the present study, TNF brought about no change in the rate of glycogen synthesis in cultured human muscle cells unless present during differentiation. The presence of TNF (5 ng/ml) during the process of differentiation of myoblasts into mature myotubes diminished the response of glycogen synthesis to acute insulin stimulation. This finding was associated with an impairment of differentiation-dependent increases in total cellular glycogen synthase (GS) activity. Under the same conditions of TNF exposure, there was no effect on the response to acute insulin stimulation of the fractional activity of GS. Similarly, there was no effect on the insulin stimulation of protein kinase B (PKB) and inhibition of glycogen synthase kinase 3 (GSK-3). Acute insulin stimulation brought about a 4.08 ؎ 0.44 -fold stimulation of activity of PKB in the absence of TNF, with 4.81 ؎ 0.70 -fold stimulation in cells exposed to TNF. GSK-3 activity decreased to 74.0 ؎ 5.8% of basal after insulin stimulation without TNF and 78.3 ؎ 5.0% after TNF exposure. However, differentiation of myocytes, as defined by an increase in the acetylcholine receptor, myogenin, and mature creatine kinase isoform expression, was impaired in TNF-treated cells. These studies demonstrate that TNF, if present during differentiation, decreases insulin-stimulated rates of storage of glucose as glycogen and total GS activity but does not downregulate the insulin-signaling system to GS. More generally, TNF also inhibits differentiation of human muscle cells in culture.
SUMMARYPlantago major grows throughout Britain in a range of ozone climates. Because populations have been shown to difFer in ozone resistance, the aim ofthe experiment was to compare the reaction of populations from contrasting ozone climates to different types of ozone exposure. Three populations were grown under controlled conditions in five difFerent ozone treatments (including controls for 10 wk. Development, growth, stomata! conductance and seed production were recorded. Populations were from the south coast of England (Lulhngton), near a mountain summit (Great Dun Fell) and lowland Scotland (Bush)-Ozone treatments were: charcoal and Purafil filtered air (CF); 35 ni I'' for 24 h every day; 70 nl I"' h for 7 h every day; C¥ then three episodes each week oi 70 nJ )"' ior 7 h; and 35 nl 1"^ continuously plus three 7 h episodes each week of 70 nl i"'.The different ozone treatments resulted in different responses in each population. Ozone promoted senescence in the Cireat Dun Fell population hut not in the others; it reduced root growth more in the Lullington population than in the others but those from Lullington and Great Dun Fell maintained seed production to a much greater extent than the Bush population. The reproductive effort (number of seeds g"' of vegetative weight) actually increased in ozone in the Lullington and Great Dun Fell populations. It is suggested that this might be a general stress response rather than being specifically related to ozone. EfFects on stomatal conductance were similar to those previously reported and the converse of effects on seed production.The relative responses of the populations varied according to the ozone treatment. Continuous exposure to 35 nl r^ reduced leaf size only in the Great Dun Fell population, but seed output was reduced in the Bush population. In some cases, giving 3-d episodes of 70 nl l"^ had a greater effect than giving the dose every day but the effects varied with the population. This greater effect was considered to be a result of the time it takes for a plant to develop maximum anti-oxidant defence, which is lost when the ozone decreases after the episode. A plant exposed to episodes might have to re-induce defence with each exposure.Although it is reported frequently that ozone favours allocation of resources to the shoot over the root, it is concluded that this is an over-simpiification of the response. Even within a species there is a compJex suite of responses that varies with the population and with ozone exposure. Describing a population as resistant or sensitive is also an over-simplification.
Hypertension and non-insulin dependent diabetes mellitus (NIDDM) co-exist in the same population and it has been postulated that the insulin resistance might be a component not only of NIDDM but also hypertension. Some support for this possibility comes from animal models through the finding that the insulin sensitizer agents BRL 49653, troglitazone and pioglitazone attenuate hypertension in a number of models of obesity (1-31.A commonly used model of hypertension is the spontaneously hypertensive (SH) rat [4]. These animals demonstrate mild hypertension at 5 weeks of age and marked hypertension by the age of 18 weeks. Previous studies to examine whether this genetic strain is insulin resistant used the Wistar Kyoto (WK) rat as a control and have produced divergent results, with some finding decreased whole body insulin sensitivity [5] and others even enhanced glucose tolerance [ 6 ] . Resistance to insulin-mediated glucose disposal in skeletal muscle in vitro has not been reported in SH rats and insulin resistance in adipocytes has only been shown in 9 week old rats when hypertension is already well established [7].In the present study we measured insulin-mediated glucose disposal in isolated skeletal muscle and insulinmediated glucose uptake in adipocytes from 3 and 5 week old male SH rats which were normotensive and 18 week old male hypertensive SH rats. Wistar Kyoto and normal Wistar (WI) rats were used as the age/sex matched controls.Adipocytes were prepared by collagenase digestion [8] prior to the determination of insulin-stimulated glucose uptake and conversion into lipid [9]. Whole soleus muscles were obtained from 3 week old animals and strips of muscles were prepared from 5 and 18 week old animals. "C-glucose conversion to glycogen was measured [lo].The adipocytes from the 3 week old SH and WK rats were hyper-responsive to insulin relative to adipocytes from WI rats. Thus the maximal rates of insulin-stimulated glucose incorporation into lipid were: SH, 11245&1264*, WK, 9021f15** and WI, 5447f803 nmoles glucose incorporated /hr/106 cells (*p < 0.02, **p < 0.005).There was no difference in the basal rate of glycogen synthesis in soleus muscle in the 3 week old rats. Furthermore, glycogen synthesis rates at the maximum insulin concentration were also similar but at submaximal concentrations of insulin, glycogen synthesis was decreased by 40% in SH and WK rats relative to WI controls (Figure 1). In the 5 week old rats basal rates of glycogen synthesis were similar in the three groups but submaximal and maximal insulin-stimulated rates were Abbreviations used: NIDDM, non-insulin dependent diabetes mellitus; SH, spontaneously hypertensive; WK, Wistar Kyoto; WI, Wistar decreased in SH and WK rats compared to WI controls (Figure 2). At 18 weeks, glycogen synthesis was reduced in WK rats at submaximal concentrations of insulin (data not shown). Figure I : Glycogen synthesis in isoluted skeletal muscle of SH, WK and WI rafs at 3 weeks of age. (Duta show me^ +_ SEM; n=5.* p < 0.02) o.+J , ...,._ ...,.ll ...,._ ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.