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Biomedical subjects

A Wennlund

Publications and source records attributed to A Wennlund.

28 records · Page 2Linked to original sources
PubMed1982

Phosphodiesterase activity in human subcutaneous adipose tissue in hyper- and hypothyroidism.

Phosphodiesterase (PDE) activity was determined in sc adipose tissue from 12 patients with untreated hyperthyroidism, 8 patients with untreated hypothyroidism, and 10 healthy nonobese subjects. Eight of the hyperthyroid group were reexamined after treatment when they were euthyroid. The apparent Vmax of the low Km form of PDE was 25% lower in untreated hyperthyroidism (P less than 0.05) and 100% higher in untreated hypothyroidism (P less than 0.01) than in the controls; treatment of the hyperthyroidism resulted in normalization of the value. There was a positive correlation between the mean fat cell volume and the Vmax of the low Km PDE in all conditions (r = 0.64-0.85). As regards the high Km form of PDE, the Vmax values for both hyper- and hypothyroid patients did not differ from those for the control group. The results of this study suggest that in man, the apparent Vmax for the PDE with low Km is determined by the thyroid hormones.

Adipose Tissue↗
PubMed1981

Post receptor activation of lipolysis in starvation, diabetes mellitus and hyperthyroidism.

Activation of lipolysis by cyclic AMP in conditions with accelerated lipid mobilization was examined in subcutaneous adipose tissue incubated in vitro. In (a) 16 obese patients before and during therapeutic starvation, (b) 18 diabetics before and after antidiabetic treatment and (c) 11 hyperthyroid patients before and after anti-thyroid treatment, a positive correlation was found between stimulation of basal cyclic AMP accumulation and stimulation of basal glycerol release using either isopropyl noradrenaline or noradrenaline (r = 0.6-0.9). During antidiabetic treatment stimulation of lipolysis increased in relation to that of cyclic AMP accumulation (F = 10.1, p less than 0.01), whereas during antithyroid therapy there was a decrease (F = 95.2, p less than 0.01). Starvation did not alter the relationship between lipolysis and cyclic AMP in hypogastric adipose tissue whereas in femoral tissue stimulation of lipolysis decreased in relation to that of cyclic AMP accumulation (F = 9.6, p less than 0.01). It is concluded that the amount of cyclic AMP needed to promote lipolysis is increased during starvation and in diabetes mellitus but is decreased in hyperthyroidism. From the studies during starvation it appears that regional differences in the post-receptor activation of lipolysis exist in human adipose tissue.

Adult↗
PubMed1981

Influence of hyperthyroidism on splanchnic exchange of glucose and gluconeogenic precursors.

Arterial concentrations and splanchnic exchange of glucose, amino acids, lactate, pyruvate, and glycerol were determined in 14 hyperthyroid patients and 12 healthy controls. Seven of the patients were restudied after 5-12 mo of medical management at which time there was chemical and clinical evidence of a euthyroid state. The arterial level of glucose was slightly higher (+10%) in the patient group and the glycerol concentration was three times greater among the patients. The plasma levels of the glycogenic amino acids, alanine, glycine, and serine were decreased by 20-30%, while the concentrations of leucine, isoleucine, and tyrosine were increased by 20-80%. The levels of lactate and pyruvate were similar in patients and controls as were insulin and glucagon concentrations. Splanchnic glucose output in the patient group was 35% lower than in controls. However, total splanchnic uptake of glucogenic precursors was 100% higher than in controls and showed a direct linear correlation with serum triiodothyronine. Total precursor uptake could account for 75% of splanchnic glucose output in the patients, compared to 26% in controls. The increase in uptake of lactate, alanine, and other amino acids was due to a 35-80% rise in splanchnic fractional extraction plus a 20% rise in estimated hepatic blood flow. When the patients were restudied after medical treatment splanchnic exchange of glucose and glucose precursors had reverted to normal values. The present findings demonstrate that in hyperthyroidism (a) total splanchnic glucose output is reduced in relation to controls, (b) splanchnic uptake of gluconeogenic precursors is accelerated, largely due to a rise in fractional extraction of precursor substrates and to a smaller extent, as a result of an increase in hepatic blood flow, and (c) these changes revert to normal when a euthyroid state has been achieved.

Adult↗
PubMed1981

Changes in the effects of insulin on human adipose tissue metabolism in hyperthyroidism.

The in vitro effects of insulin on glycerol release and glucose incorporation into neutral lipids (lipogenesis) were studied in segments of sc adipose tissue obtained from 9 control subjects and 11 patients with hyperthyroidism; 6 patients were reinvestigated after treatment. In untreated hyperthyroidism, there was a decreased sensitivity to the antilipolytic effect of insulin, since the dose-response curve was shifted to the right; 250 microU/ml insulin were required for 50% of the maximal effect compared to 25 microU/ml in the controls. During antithyroid therapy, the dose-response curve normalized. Insulin caused a 25% increase in lipogenesis in the untreated hyperthyroid patients, but no consistent effect was seen in the control subject or in hyperthyroid patients during treatment.

Adipose Tissue↗
PubMed1981

Thyroid hormone regulation of the catecholamine effects in human adipose tissue.

The possibility of a relationship between the thyroid hormone level and the peripheral action of catecholamines was examined in 4 normal-weight and 19 obese euthyroid subjects as well as in 27 hyperthyroid subjects by comparing the serum thyroid hormone level and the in vitro effect of catecholamines on lipolysis and cyclic AMP accumulation in adipose tissue incubated with and without isopropyl noradrenaline (ISNA) or noradrenaline (NA). ISNA- and NA-induced rates of lipolysis and cyclic AMP production were significantly correlated with free thyroxine index (r = 0.63-0.74) and with the serum triiodothyronine level (r = 0.83-0.87). The thyroid hormone level was neither correlated with basal rate of lipolysis nor with basal cyclic AMP production (r < 0.2). These results suggest that the magnitude of catecholamine-induced cyclic AMP production by peripheral cells may be regulated by the level of circulating thyroid hormones. The effect of thyroid hormones on lipolysis appears to be specifically linked to the action of catecholamines.

Adipose Tissue↗
PubMed1981

Regulation of lipolysis in hyperthyroidism.

The investigation (Fig. 1) clearly shows that the ability of isoprenaline in particular and, to a less extent, of noradrenaline to increase the accumulation of cyclic AMP and thus also the rate of lipolysis is enhanced in hyperthyroidism. No evidence was found of changes in the sensitivity to either beta 1- or alpha -adrenergic agonists. Although further studies are needed, the findings supported the idea that the augmented cyclic AMP accumulation is due to changes below the receptor level. Second, a significant decrease was observed in the apparent Vmax of the PDE with apparent low Km. Third, metabolic disturbances closer to the lipolytic system may exist. Some indirect evidence for this hypothesis was the finding of relatively more rapid lipolysis in relation to the cyclic AMP level in hyperthyroidism. The investigations have raised a number of questions about the nature of the metabolic changes in hyperthyroidism. The findings suggest that there are multiple abnormalities, localized at different levels of mechanisms regulating lipid mobilization. Investigations of subcutaneous tissue fragments in man seem to offer good opportunities for exploring these abnormalities.

Adrenergic alpha-Agonists↗
PubMed1979

Regulation of lipolysis by human adipose tissue in hyperthyroidism.

The effects of noradrenaline (NA) and isopropyl-noradrenaline (ISNA) on glycerol release and cAMP levels in sc adipose tissue were studied in vitro in 27 patients with hyperthyroidism. In 11 patients, the studies were repeated after 6--12 months of treatment for hyperthyroidism. A third group comprised 21 euthyroid patients otherwise healthy except for morbid obesity. The lipolytic response to ISNA, observed in untreated thyrotoxic patients, was found to be reduced by 30% when the patients were reexamined after treatment for thyrotoxicosis. This reduction was attributable to a decrease in the cAMP level. This was observed whether adipose tissue was incubated in the presence or absence of a phosphodiesterase inhibitor, theophylline. Both NA and ISNA induced 50% more rapid glycerol release and 4 times higher cAMP levels in adipose tissue of the thyrotoxic subjects than in the obese euthyroid patients. A positive correlation between tissue cAMP and glycerol release, on one hand, and mean fat cell size, on the other hand, was observed in treated thyrotoxic patients and obese euthyroid patients but was not recorded in the untreated hyperthyroid patients. The basal rate of lipolysis was not altered in thyrotoxicosis. The results suggest that the enhanced lipolytic response to catecholamines in adipose tissue of hyperthyroid patients is due to increased beta-adrenergic responsiveness. In addition, a disruption in subsequent stages of the regulatory pathway at the level of protein kinase or hormone-sensitive lipase also seems possible.

Adipose Tissue↗
PubMedDate not supplied

A marked upregulation of uncoupling protein 2 gene expression in adipose tissue of hyperthyroid subjects.

Recently, a family of uncoupling protein (UCP) genes has been discovered. The role of these genes is unknown, but it has been suggested that they are involved in regulating resting metabolic rate. In this study, we hypothesised that thyroid hormone status may influence the expression of UCP2 mRNA. The adipose tissue levels of UCP2 mRNA were measured in eight female subjects before and after treatment for thyrotoxicosis. All subjects in the hyperthyroid condition had markedly enhanced plasma levels of thyroxine (62.0 +/- 6.9 vs. 17.9 +/- 1.7, p = 0.012) and triiodothyronine (37.9 +/- 6.9 vs. 5.9 +/- 0.9, p = 0.012), accelerated heart rate (94 +/- 7 vs. 69 +/- 5, p = 0.012), decreased BMI (24.5 +/- 1.9 vs. 25.1 +/- 1.9, p = 0.025) and decreased percentage body fat (32.8 +/- 4.4 vs. 37.1 +/- 4.5, p = 0.018), as compared to the euthyroid state. Using RT-competitive-PCR, the UCP2 mRNA levels were found to be 2.5-fold upregulated in hyperthyroidism (10.4 +/- 1.7 vs. 4.2 +/- 1.3 amol/microg RNA, p = 0.012). In contrast, no difference in expression levels of the reference gene 18SrRNA was seen in the hyperthyroid versus the euthyroid state (317 +/- 49 vs. 279 +/- 25 amol/microg RNA, p = 0.48) but the difference in UCP2 mRNA levels between the hyper- and euthyroid state remained when UCP2 was related to 18SrRNA (p = 0.012). In conclusion, thyrotoxicosis markedly increases the expression of UCP2 mRNA in adipose tissue, which suggests a role for thyroid hormones in the regulation of this uncoupling protein in man.

Adipose Tissue↗