Does hyperinsulinemia in ob/ob mice cause an insulin-stimulated adipose tissue?

1976 ◽  
Vol 230 (3) ◽  
pp. 602-607 ◽  
Author(s):  
EG Loten ◽  
Y Le Marchand ◽  
F Assimacopoulos-Jeannet ◽  
RM Denton ◽  
B Jeanrenaud

After a 1-h preincubation to remove endogenous insulin, adipose tissue of obese mice (C57BL/L4 ob/ob) had a lower rate of glucose metabolism than tissue which was not preincubated. In contrast, preincubation did not change the metabolism of adipose tissue from lean mice (C57B1/6J +/+). The preincubation effect was abolished in obese mice which had had their serum insulin levels lowered toward normal by streptozotocin treatment. Injection of anti-insulin serum to obese mice caused adipose tissue removed 15 min after the injection to display a rate of glucose metabolsim lower than that of tissue removed before the injection. No such effect was seen in lean mice. These data are consistent with the hypothesis that hyperinsulinemia in the obese mice causes a chronic state of insulin stimulation of their adipose tissue, possibly contributing to their high rates of lipogenesis and their obesity. Several lipogenic enzymes were measured in adipose tissue of both lean and obese mice, and no single enzymatic abnormality was detected which might explain the hyperlipogenesis. Pyruvate dehydrogenase and acetyl-CoA carboxylase were both insulin-sensitive enzymes in lean and obese mice.

1990 ◽  
Vol 265 (2) ◽  
pp. 511-517 ◽  
Author(s):  
A F Burnol ◽  
S Ebner ◽  
J Kandé ◽  
J Girard

The mechanism responsible for the insulin resistance described in vivo in brown adipose tissue (BAT) of lactating rats was investigated. The effect of insulin on glucose metabolism was studied on isolated brown adipocytes of non-lactating and lactating rats. Insulin stimulation of total glucose metabolism is 50% less in brown adipocytes from lactating than from non-lactating rats. This reflects a decreased effect of insulin on glucose oxidation and lipogenesis. However, the effect of noradrenaline (8 microM) on glucose metabolism was preserved in brown adipocytes from lactating rats as compared with non-lactating rats. The number of insulin receptors is similar in BAT of lactating and non-lactating rats. The insulin-receptor tyrosine kinase activity is not altered during lactation, for receptor autophosphorylation as well as tyrosine kinase activity towards the synthetic peptide poly(Glu4-Tyr1). The defect in the action of insulin is thus localized at a post-receptor level. The insulin stimulation of pyruvate dehydrogenase activity during euglycaemic/hyperinsulinaemic clamps is 2-fold lower in BAT from lactating than from non-lactating rats. However, the percentage of active form of pyruvate dehydrogenase is similar in non-lactating and lactating rats (8.6% versus 8.9% in the basal state, and 37.0% versus 32.3% during the clamp). A decrease in the amount of pyruvate dehydrogenase is likely to be involved in the insulin resistance described in BAT during lactation.


1964 ◽  
Vol 28 (2) ◽  
pp. 163-172 ◽  
Author(s):  
J. G. T. SNEYD

SUMMARY The insulin content of the pancreas and the insulin-like activity of the blood serum are considerably higher in mice of the New Zealand obese strain than in normal controls. The rate of glucose uptake by adipose tissue and hemi-diaphragms incubated in the absence of added insulin did not differ significantly in tissues from obese and normal mice and the stimulation of glucose uptake caused by addition of insulin was similar in tissues from the two strains. Insulin extracted from the pancreas of New Zealand obese mice stimulated glucose uptake by adipose tissue and muscle from obese mice to the same extent as an equivalent amount of porcine insulin.


1988 ◽  
Vol 255 (4) ◽  
pp. E567-E571 ◽  
Author(s):  
S. B. Waters ◽  
J. A. Rillema

Prolactin (PRL) stimulates an increased rate of incorporation of [14C]acetate and [3H]glucose into lipids in cultured mammary gland explants from 10- to 14-day-pregnant mice. This response is biphasic with an early increase occurring from 6 through 12 h, and an additional increase from 16 through 24 h. Enzymes likely to be rate limiting to this process include acetyl CoA carboxylase, fatty acid synthetase, acetyl CoA synthetase, and/or pyruvate dehydrogenase. Of these enzymes only pyruvate dehydrogenase activity was elevated at 6 h, suggesting that this enzymatic activity is important in stimulating early increases in lipogenesis after PRL treatment. In addition, the PRL stimulation of pyruvate dehydrogenase may also indirectly stimulate acetyl CoA carboxylase through the generation of citrate; this may explain the early (6-12 h) effect of PRL on [14C]acetate incorporation. After 16 h of PRL treatment, the activities of all the lipogenic enzymes were enhanced. The second phase of PRLs stimulation of lipogenesis thus likely involves the enhanced activities of more than one of the lipogenic enzymes.


2003 ◽  
Vol 369 (2) ◽  
pp. 351-356 ◽  
Author(s):  
Sam A. JOHNSON ◽  
Richard M. DENTON

In isolated rat adipocytes, the insulin stimulation of pyruvate dehydrogenase can be partially inhibited by inhibitors of PI3K (phosphoinositide 3-kinase) and MEK1/2 (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase). In combination, U0126 and wortmannin completely block the insulin stimulation of pyruvate dehydrogenase. It is concluded that the effect of insulin on pyruvate dehydrogenase in rat adipocytes involves two distinct signalling pathways: one is sensitive to wortmannin and the other to U0126. The synthetic phosphoinositolglycan PIG41 can activate pyruvate dehydrogenase but the activation is only approx. 30% of the maximal effect of insulin. This modest activation can be completely blocked by wortmannin alone, suggesting that PIG41 acts through only one of the pathways leading to the activation of pyruvate dehydrogenase.


Author(s):  
C. Loriette ◽  
M. Launay ◽  
D. Lapous ◽  
J. Raulin

ABSTRACT:The present experiment was carried out using the following diets:FF, fat-free, andLPthe same diet with 0.7% sunflower oil - given to the progeny of females kept on theFFdiet since the mating. After 10 mM Mg2+ activation of the PDH phosphatase, the rate of [1-14C] pyruvate decarboxylation into acetyl-CoA ester units was determined in the liver, brain and adipose-tissue of the pair-fed developing rats.Results: In the male progeny, pyruvate dehydrogenase (PDH) activity was higher (61%) in theLPgroup livers than in theFFgroup livers, at the end of the 13 week experiment. Such a difference was not observed in the two group brains up to the 91 days postweaning, but was even larger (94%) between adipose-tissues of theLPandFFgroups. In the female progeny kept 12 weeks on the diets, PDH activity in theLPgroup tissues was also higher than in theFFgroup tissues: 63% in the liver, 43% in adipose-tissues, and less than 10% in the brain. Therefore, a minute amount of lipids high in linoleic acid appeared to increase PDH activity, and especially in the liver and adipose-tissues of animals kept on a strictly fat-free diet. This stimulation of the PDH activity seems closely related to the phospholipid rehabilitation in the tissues (decrease in the trienoic: tetraenoic acid ratio values).


1983 ◽  
Vol 210 (3) ◽  
pp. 677-683 ◽  
Author(s):  
J P Robertson ◽  
A Faulkner ◽  
R G Vernon

1. The following were measured in pieces of perirenal adipose tissue obtained from foetal lambs at about 120 days of gestation or within 3 days of term, and 9-month-old sheep: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2 and the proportions contributed by the pentose phosphate cycle, pyruvate dehydrogenase and the tricarboxylic acid cycle; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase. 2. The total rate of glucose utilization was lower in pieces of adipose tissue from near-term lambs than 120-day foetal lambs and the pattern of glucose metabolism differed, with, for example, a much smaller proportion of glucose carbon being used for fatty acid synthesis, whereas a greater proportion of glucose oxidation occurred via the tricarboxylic acid cycle in the near-term lambs. In general, these differences in glucose metabolism were not associated with differences in the activities of the various enzymes listed above. 3. The rates of glucose utilization per fat-cell by 120-day foetal lambs and 9-month-old sheep were very similar but, again, the proportions metabolized to the various products differed. In particular, there was a smaller proportion of glucose oxidized via the pentose phosphate cycle and a greater proportion oxidized via pyruvate dehydrogenase and the tricarboxylic acid cycle in adipose tissue from foetal lambs. These differences were matched by a lower activity of glucose 6-phosphate dehydrogenase and a higher pyruvate dehydrogenase activity in fat-cells from the foetal lambs.


Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 1998-2007 ◽  
Author(s):  
Matthew C. Ernst ◽  
Mark Issa ◽  
Kerry B. Goralski ◽  
Christopher J. Sinal

Obesity, characterized by an excess of adipose tissue, is an established risk factor for cardiovascular disease and type 2 diabetes. Different mechanisms linking obesity with these comorbidities have been postulated but remain poorly understood. Adipose tissue secretes a number of hormone-like compounds, termed adipokines, that are important for the maintenance of normal glucose metabolism. Alterations in the secretion of adipokines with obesity are believed to contribute to the undesirable changes in glucose metabolism that ultimately result in the development of type 2 diabetes. In the present study, we have shown that serum levels of the novel adipokine chemerin are significantly elevated in mouse models of obesity/diabetes. The expression of chemerin and its receptors, chemokine-like receptor 1, chemokine (C-C motif) receptor-like 2, and G protein-coupled receptor 1 are altered in white adipose, skeletal muscle, and liver tissue of obese/diabetic mice. Administration of exogenous chemerin exacerbates glucose intolerance, lowers serum insulin levels, and decreases tissue glucose uptake in obese/diabetic but not normoglycemic mice. Collectively, these data indicate that chemerin influences glucose homeostasis and may contribute to the metabolic derangements characteristic of obesity and type 2 diabetes.


2020 ◽  
Vol 29 (8) ◽  
pp. 488-497 ◽  
Author(s):  
Masayoshi Ishida ◽  
Kohei Tatsumi ◽  
Katsumi Okumoto ◽  
Hiroshi Kaji

1997 ◽  
Vol 77 (1) ◽  
pp. 173-175 ◽  
Author(s):  
E. K. Okine ◽  
P. F. Arthur

The effects of feeding isoenergetic barley grain or alfalfa pellets on in vitro lipogenesis, palmitate esterification, and lipogenic enzymes activities in biopsy samples of subcutaneous adipose tissue in 10 ewes were studied. Acetyl CoA carboxylase and FAS activities and rate of esterification were 52, 38, and 88%, respectively, higher (P < 0.05) in subcutaneous adipose of ewes fed the concentrate versus those fed the roughage diet. Key words: Isoenergetic, adipose tissue, acetyl CoA carboxylase


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