Spontaneous obesity and weight loss: insulin binding and lipogenesis in the dormouse

1983 ◽  
Vol 245 (3) ◽  
pp. R403-R407
Author(s):  
R. B. Melnyk ◽  
N. Mrosovsky ◽  
J. M. Martin
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Glucose Utilization ◽  
Binding Capacity ◽  
Insulin Binding ◽  
Glis Glis ◽  
Severe Insulin Resistance ◽  
Impaired Insulin ◽  
Receptor Concentration ◽  
Isolated Adipocytes

Obese dormice (Glis glis) become anorexic during the weight loss phase of the 2-mo (infradian) body weight cycle. We have shown previously that this phase is characterized by severe insulin resistance, manifested by impaired insulin-stimulated glucose utilization in isolated adipocytes. Contrary to other obesity models, the insulin resistance was not accompanied by hyperinsulinism. In the present study, impaired lipogenesis was associated with decreased maximal insulin-binding capacity (due to a reduction in receptor concentration) and a postreceptor defect, which were exacerbated rather than attenuated during weight loss.

Characterization of the insulin resistance of glucose utilization in adipocytes from patients with hyper- and hypothyroidism

1988 ◽  
Vol 119 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Oluf Pedersen ◽  
Bjørn Richelsen ◽  
Jens Bak ◽  
Jon Arnfred ◽  
Jørgen Weeke ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Transport ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Insulin Binding ◽  
Oxidation Rates ◽  
Impaired Insulin ◽  
Insulin Responsiveness ◽  
Hypothyroid Patients

Abstract. Insulin action on glucose utilization was characterized in adipocytes from 10 thyrotoxic patients, 6 hypothyroid patients and 10 age- and sex-matched control subjects. In thyrotoxic patients insulin binding at low insulin concentrations was reduced (P < 0.05) and accompanied by impaired insulin sensitivity of glucose transport (P < 0.02), glucose oxidation (P < 0.05) and lipogenesis (P < 0.05). Glucose transport and glucose oxidation rates also exhibited depressed maximal insulin responsiveness (P < 0.05). In hypothyroid patients insulin binding was reduced, too, (P < 0.05) and associated with impaired sensitivity to insulin of glucose transport (P < 0.05). Both glucose transport and lipogenesis rates showed decreased maximal insulin responsiveness (P < 0.05). In conclusion: In man, both hyper- and hypothyroidism are characterized by insulin resistance of adipocyte glucose utilization localized to insulin binding as well as to insulin-stimulated glucose transport and metabolism.

Insulin and central regulation of spontaneous fattening and weight loss

1985 ◽  
Vol 249 (2) ◽  
pp. R203-R208
Author(s):  
R. B. Melnyk ◽  
J. M. Martin
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Weight Gain ◽  
Energy Balance ◽  
Binding Capacity ◽  
Insulin Receptors ◽  
Insulin Binding ◽  
Strong Positive Correlation ◽  
Central Regulation ◽  
Isolated Pancreatic Islets

Insulin binding to receptors in a partially purified hypothalamic membrane preparation is altered by prolonged starvation. To define further the relationship between hypothalamic insulin binding and energy balance, we studied the Richardson's ground squirrel, a hibernator that exhibits spontaneous 6- to 8-mo body weight cycles when kept in constant conditions. Isolated pancreatic islets from squirrels killed during the weight gain phase had greater glucose-stimulated insulin secretion than those from weight loss phase animals, and adipocytes showed significantly greater glucose incorporation into total lipid in response to insulin. Differences in lipogenesis were not attributable to changes in insulin-binding capacity. Hypothalamic tissue from weight gain phase animals bound more insulin than that from weight loss phase animals. Maximal binding was correlated with pancreatic islet responsiveness and maximal insulin-stimulated lipogenesis. The strong positive correlation between peripheral metabolic events associated with spontaneous alterations in energy balance and the binding kinetics of hypothalamic insulin receptors suggests that insulin may play an important role in the central regulation of body weight.

scholarly journals Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss

2007 ◽  
Vol 157 (4) ◽  
pp. 465-471 ◽  
Author(s):  
Jens M Bruun ◽  
Bente Stallknecht ◽  
Jørn W Helge ◽  
Bjørn Richelsen
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Rt Pcr ◽  
Reduced Body ◽  
Daily Exercise ◽  
Life Style Intervention ◽  
Obese Subjects ◽  
Isolated Adipocytes

Objective: Interleukin (IL)-18 is associated with obesity, insulin resistance, and cardiovascular disease. The present study compared 1) IL-18 in adipocytes versus stromal vascular (SV) cells, 2) IL-18 in plasma and adipose tissue (AT) in obese versus lean subjects, and 3) IL-18 in plasma, AT, and skeletal muscle (SM) in obese subjects after weight loss. Subjects and methods: At baseline, plasma and AT IL-18 in 23 obese subjects were compared with that in 12 lean subjects. The obese subjects were submitted to a 15-week life-style intervention (hypocaloric diet and daily exercise) after which plasma samples, AT, and SM biopsies were obtained. Analyses were performed by ELISA and RT-PCR respectively. Results: IL-18 expression in isolated adipocytes was ~2% of that in SV cells. Plasma IL-18 was higher in obese subjects (P < 0.001) and associated with insulin resistance (HOMA; P < 0.001). AT expression of IL-18, CD14, and CD68 was higher in obese (P < 0.01). The intervention reduced body weight (P < 0.001), plasma IL-18 (P < 0.001), and increased insulin sensitivity (HOMA; P < 0.05). AT and SM expression of IL-18 remained unchanged after the intervention. Changes in plasma IL-18 were associated with changes in insulin sensitivity (P < 0.05) but not with BMI or AT expression of IL-18. Conclusion: Plasma IL-18 is associated with changes in insulin resistance and reduced after weight loss. AT expression of IL-18 is increased in obesity but not affected by weight loss, indicating that changes in plasma IL-18 are related to insulin resistance rather than changes in obesity per se.

scholarly journals Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance

2009 ◽  
Vol 94 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Vanita Aroda ◽  
Sunder Mudaliar ◽  
R. Jeffrey Chang ◽  
Robert R. Henry
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Glucose Disposal ◽  
Signaling Proteins ◽  
Impaired Insulin ◽  
Isolated Adipocytes ◽  
Insulin Responsiveness

Abstract Objective: The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS). Research Design and Methods: Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins. Results: Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P &lt; 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P &lt; 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes. Conclusions: Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.

Leptin inhibits insulin binding in isolated rat adipocytes

1997 ◽  
Vol 155 (3) ◽  
pp. R5-R7 ◽  
Author(s):  
K Walder ◽  
A Filippis ◽  
S Clark ◽  
P Zimmet ◽  
GR Collier
Keyword(s):  
Insulin Resistance ◽  
Body Fat ◽  
Insulin Binding ◽  
The Body ◽  
Displacement Curve ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Binding Data ◽  
Isolated Adipocytes ◽  
Dose Dependent

Leptin is secreted from adipose tissue, and is thought to act as a 'lipostat', signalling the body fat levels to the hypothalamus resulting in adjustments to food intake and energy expenditure to maintain body weight homeostasis. In addition, plasma leptin concentrations have been shown to be related to insulin sensitivity independent of body fat content, suggesting that the hyperleptinemia found in obesity could contribute to the insulin resistance. We investigated the effects of leptin on insulin binding by isolated adipocytes. Adipocytes isolated from Sprague-Dawley rats exhibited a dose-dependent reduction in the uptake of 125I-labelled insulin when incubated with various concentrations of exogenous leptin. For example, addition of 50 nM leptin reduced total insulin binding in isolated adipocytes by 19% (P < 0.05). Analysis of displacement curve binding data suggested that leptin reduced maximal insulin binding in a dose-dependent manner, but had no significant effect on the affinity of insulin for its binding site. We conclude that leptin directly inhibited insulin binding by adipocytes, and the role of leptin in the development of insulin resistance in obese individuals requires further investigation.

Metformin ameliorates extreme insulin resistance in a patient with anti-insulin receptor antibodies: description of insulin receptor and postreceptor effects in vivo and in vitro

1992 ◽  
Vol 126 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Salvatore Di Paolo
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Glucose Transport ◽  
Insulin Binding ◽  
Severe Insulin Resistance ◽  
Binding Data ◽  
Extreme Insulin Resistance ◽  
Receptor Antibodies

The effect of metformin on insulin binding and insulin action in the presence of anti-insulin receptor antibodies was investigated in a case of type B extreme insulin resistance. Oral administration of metformin (1 500 mg/d) for 10 days significantly decreased plasma blood glucose and insulin levels and enhanced the hypoglycemic response to exogenous insulin. In vitro preincubation of normal erythrocytes with insulin receptor antibody from the patient plus 4× 10−5 mol/l metformin markedly enhanced insulin binding to receptors, compared to cells incubated with antibody alone. This effect was apparent after 2 h, was maximal after 4 h and did not change up to 24 h. Closely similar results were found when human adipocytes were studied. Analysis of binding data confirmed the increase in both receptor number and affinity. One hour exposure of control adipocytes to metformin enhanced basal lipogenesis by more than 30%. Acute exposure of fat cells to the patient's receptor antibodies resulted in a stimulation of glucose transport and a state of severe insulin resistance. The addition of metformin to antibody in preincubation buffer strongly enhanced basal glucose incorporation into lipids, but did not prevent insulin unresponsiveness. It is suggested that metformin increases, possibly through a change in the spatial conformation of insulin receptor within the plasma membrane, the availability of preexisting receptors to insulin binding and/or decreases the availability of specific epitopes to antibody anchoring. Further, in the model of insulin resistance described here, metformin enhanced the basal rate of glucose transport through a direct insulin-mimicking activity and/or a potentiation of the sensitivity of glucose transport to the antibody.

Autophosphorylation and kinase activity of insulin receptor in diabetic rats

1986 ◽  
Vol 251 (5) ◽  
pp. E542-E550
Author(s):  
M. Okamoto ◽  
M. F. White ◽  
R. Maron ◽  
C. R. Kahn
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Insulin Treatment ◽  
Kinase Activity ◽  
Binding Capacity ◽  
Insulin Binding ◽  
Diabetic Rats ◽  
Beta Subunit ◽  
Bb Rat ◽  
Diabetic State

Insulin resistance is observed in insulin-deficient diabetic states in spite of an increase in insulin binding to its target cells. To characterize this type of insulin resistance, autophosphorylation and kinase activity of the insulin receptor on liver was studied with streptozotocin (STZ)-induced and BB diabetic rats. Insulin binding capacity was increased in proportion to the severity of the diabetic state in the STZ rat. In the diabetic BB rat, the insulin binding capacity was also increased, and this was partially normalized by insulin treatment. By contrast, insulin-stimulated autophosphorylation of the beta-subunit of the insulin receptor was decreased in proportion to the severity of the diabetic state in the STZ rat. Peptide mapping by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. Kinase activity of the insulin receptor to exogenous substrates was also decreased in proportion to the diabetic state. In the BB rat, autophosphorylation and kinase activity of the insulin receptor were both decreased in the diabetic state and partially normalized by insulin treatment. In addition to the beta-subunit of insulin receptor, a 170 kdalton phosphotyrosine-containing protein was also identified in the glycoprotein fraction of liver. Although the phosphorylation of this protein was not insulin dependent, it was decreased markedly in the diabetic state. This protein is immunologically distinct from the insulin receptor, but is rich in phosphotyrosine. Based on its size and phosphotyrosine content, this protein may be the epidermal growth factor receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

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