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L A Gavin

Publications and source records attributed to L A Gavin.

At least 37 records · Page 2Linked to original sources
PubMed1990

Cyclic adenosine 3',5'-monophosphate and glucose stimulate thyroxine 5'-deiodinase type II in cultured mouse neuroblastoma cells.

Nutrient modulation increases mouse neuroblastoma (NB) T4-5'-deiodinase II (T4-5'-D II) activity. Carbohydrates are more potent than either amino acids or glycerol as nutrient sources. Glucose rapidly (2 to 4 hours) enhances NB enzyme activity and the response is dependent on new protein synthesis. The present study was performed to further characterize this glucose effect and explore its relationship to the cyclic adenosine monophosphate (cAMP) system in these cells. NB T4-5'-D II activity reached a maximum level (sixfold) in response to glucose (10 mmol/L) at 16 hours and thereafter remained constant up to 22 hours before reverting back to basal level between 24 and 30 hours. This pattern of response allowed the performance of detailed studies on maximum glucose activated NB T4-5'-D II under transient equilibrium conditions during the 16- to 22-hour period. Addition of dibutyryl cAMP (dbcAMP) (1 mmol/L) at this stage significantly increased enzyme activity (twofold at 2 hours and fourfold at 4 and 6 hours) compared with glucose alone. There was an additive response to dbcAMP under these maximum glucose-activated conditions. Nonactivated NB T4-5'-D II showed a twofold response to dbcAMP (1 mmol/L) at 4 hours in a glucose-free medium. Under these conditions, glucose (10 mmol/L) also increased enzyme activity twofold. Combined studies with dbcAMP and glucose increased enzyme activity fourfold at 4 hours. Subsequent studies were performed with forskolin (10 mumol/L) and cholera toxin (1 nmol/L), modulators of endogenous cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Persistence of the hypertriglyceridemic effect of tumor necrosis factor despite development of tachyphylaxis to its anorectic/cachectic effects in rats.

The administration of a single injection of tumor necrosis factor (TNF) produces a variety of acute and sustained biological effects, including hyperlipidemia, stimulation of hepatic lipogenesis, decreases in adipose tissue lipoprotein lipase activity, and anorexia with weight loss. Chronic administration of a fixed dose of TNF produces tachyphylaxis to the anorectic/cachectic effects of TNF. We now report that the hyperlipidemic effect of TNF persists during chronic TNF administration in the absence of any cachectic effect of TNF. Sprague-Dawley rats injected with TNF (250 micrograms/kg) show a significant decrease in weight over the next 24 h which can be accounted for by decreases in food and water intake accompanied by an increase in urine output. With subsequent daily injections of TNF, treated rats begin eating and rapidly regain weight. Hypertriglyceridemia persists for up to 10 days of daily injections of TNF. After three daily injections of TNF, no decreases were seen in lipoprotein lipase activity in a wide variety of tissues. De novo hepatic lipogenesis remained increased in TNF-treated animals after four daily injections, but by the fifth day hepatic lipogenesis returned to normal. After 5 days of TNF treatment the acute incorporation of labeled glycerol into serum triglycerides remained elevated. These data indicate that hyperlipidemia persists during multiple daily injections of TNF and that TNF induced hypertriglyceridemia is not inevitably linked to the syndrome of cachexia.

Animals↗
PubMed1989

Thyroxine transport and distribution in Nagase analbuminemic rats.

The postulate that thyroxine (T4) in plasma enters tissues by protein-mediated transport or enhanced dissociation from plasma-binding proteins leads to the conclusion that almost all T4 uptake by tissues in the rat occurs via the pool of albumin-bound T4 (Pardridge, W. M., B. N. Premachandra, and G. Fierer. 1985. Am. J. Physiol. 248:G545-G550). To directly test this postulate, and to test more generally whether albumin might play a special role in T4 transport in the rat, we performed in vivo kinetics studies in six Nagase analbuminemic rats and in six control rats, all of whom had similar serum T4 concentrations and percent free T4 values. Evaluation of the plasma disappearance curves of simultaneously injected 125I-T4 and 131I-albumin indicated that the flux of T4 from the extracellular compartment into the rapidly exchangeable intracellular compartment was similar in the analbuminemic rats (51 +/- 21 ng/min, mean +/- SD) and in the control rats (54 +/- 15 ng/min), as was the size of the rapidly exchangeable intracellular pool of T4 (1.13 +/- 0.53 vs. 1.22 +/- 0.36 micrograms). This latter finding was confirmed by direct analysis of tissue samples (liver, kidney, and brain). We also performed in vitro kinetics studies using the isolated perfused rat liver. The single-pass fractional extraction by normal rat liver of T4 in pooled analbuminemic rat serum was indistinguishable from that of T4 in pooled control rat serum (10.9 +/- 3.3%, n = 3, vs. 11.4 +/- 3.4%). When greater than 98% of the albumin was removed from normal rat serum by chromatography with Affi-Gel blue, the single-pass fractional extraction of T4 (measured by a bolus injection method) did not change (16.3 +/- 2.1%, n = 5, vs. 15.2 +/- 2.5%). These data provide the first valid experimental test of the enhanced dissociation hypothesis and indicate that there is no special, substantive role for albumin in T4 transport in the rat.

Animals↗
PubMed1989

Effect of tumor necrosis factor (TNF) on lipid metabolism in the diabetic rat. Evidence that inhibition of adipose tissue lipoprotein lipase activity is not required for TNF-induced hyperlipidemia.

Tumor necrosis factor (TNF) administration produces an increase in plasma triglycerides that may be due to inhibition of adipose lipoprotein lipase activity and/or a stimulation of hepatic lipogenesis. We now report that TNF administration to insulinopenic diabetic rats increases serum triglycerides (2 h, 2.4-fold; 17 h, 4.3-fold). Adipose tissue lipoprotein lipase activity was markedly decreased in diabetic animals compared with controls and was not further inhibited by TNF. Incorporation of tritiated water into fatty acids in the liver was increased 45% 1-2 h after TNF and 87% at 16-17 h. These results indicate that the TNF-induced increase in circulating lipid levels can occur in the absence of a TNF-induced inhibition of adipose tissue lipoprotein lipase activity. Moreover, the clearance from the circulation of triglycerides in chylomicrons was similar in control and TNF-treated animals; these results provide further evidence that the removal of triglyceride-rich lipoproteins is not altered in the TNF-treated animals. Our data suggest that the TNF-induced stimulation of hepatic lipid synthesis may play an important role in the increase in serum triglycerides. In addition, TNF administration to diabetic animals leads to an elevation in serum glucose levels (73% at 17 h) without a change in serum insulin levels. Thus, TNF stimulation of hepatic lipogenesis is independent of changes in insulin.

Adipose Tissue↗
PubMed1989

Carbohydrate reactivation of thyroxine 5'-deiodinase (type II) in cultured mouse neuroblastoma cells is dependent upon new protein synthesis.

The T3 concentration in brain predominantly reflects local production from T4 rather than T3 uptake from the circulating pool. We recently demonstrated that rat brain T3 content is increased by glucose feeding compared to chow feeding. One possible mechanism for this effect is an increase in brain T4 5'-deiodinase (5'-D) activity. Our recent preliminary studies of neuroblastoma (NB) cells demonstrate that renewal of RPMI-1640 medium stimulates T4 5'-D type II (NB T4 5'-D II) activity in these cells. The present studies were performed to determine the mechanism of this response. Studies were performed on NB cells supported in thyroid hormone-depleted (deficient) medium. This approach increased NB T4 5'-DII activity 4-fold compared to that in thyroid hormone-replete medium. Medium renewal further stimulated enzyme activity (7- to 9-fold; maximum at 6 h) in each group. The difference between the hypothyroid group and control was sustained over a 24-h period. Subsequent studies demonstrated that glucose (11 mM) was the specific medium ingredient mediating the medium renewal response. A progressive increase in NB T4 5'-DII activity was noted over 8 h during RPMI-1640 salt plus glucose (11 mM) incubation. This was equivalent to the effect of complete medium containing glucose (11 mM). Coincubation with insulin (10(-7)-10(-9) M) did not modify the enzyme response to glucose. In addition, fructose (10 mM) had a similar effect on enzyme activity. Glycerol and essential and nonessential amino acids also modestly increased NB T4 5'-DII activity compared to that in the control group (P less than 0.01). Actinomycin-D (1 microM), cycloheximide (100 microM), and puromycin (100 microM) significantly (P less than 0.001) decreased the glucose effect on T4 5'-DII by 5-, 9-, and 17-fold, respectively, after 6 h of incubation. In addition, puromycin (10-200 microM) inhibited both NB T4 5'-DII activity and [3H]amino acid incorporation during incubation in glucose. There was a significant correlation between these parameters (r = 0.8; P less than 0.001). The enzyme activity decay curves in the glucose-activated and control groups subsequent to puromycin (100 microM) addition at 8 h were parallel. The fractional turnover rate was 13%/h in the controls and 11%/h in the glucose groups. The calculated enzyme production rate was significantly higher (P less than 0.005) in the glucose group compared to that in the control group (17.4 vs. 6.8 fmol/mg protein.h).(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1989

Management of diabetes mellitus during surgery.

Patients with diabetes mellitus are subjected to major operations more frequently than those without diabetes. Although many of these operations are done on an elective basis, the perioperative control of blood glucose levels--ranging from 6.7 to 13.3 mmol per liter (120 to 240 mg per dl)--remains a therapeutic challenge. In planning the management, the type of diabetes, current treatment, the degree of recent control, the presence of complications, and the type of surgical procedure must all be considered. All insulin-dependent patients and many non-insulin-dependent ones need insulin therapy perioperatively. The variable stress associated with major procedures such as coronary artery bypass and kidney transplantation makes a flexible insulin regimen desirable, which can be provided using a continuous insulin (regular) infusion system and frequent bedside blood glucose monitoring. Implementing such a regimen facilitates rapid control before an operation and a quick response to blood glucose changes during the procedure and provides a convenient and predictable method of control during the postoperative period.

Diabetes Mellitus↗
PubMed1989

Effect of tumor necrosis factor administration in vivo on lipoprotein lipase activity in various tissues of the rat.

When added to murine adipocytes in culture, tumor necrosis factor (TNF) decreases the levels of lipoprotein lipase (LPL). Semb et al (1987. J. Biol Chem. 262: 8390-8394) have shown that administration of murine TNF to rats decreases lipoprotein lipase (LPL) in the epididymal fat pad with maximal inhibition requiring several hours. We have now tested the effects of treatment of rats with TNF on LPL activity in a variety of tissues and find that few show decreases in LPL under conditions that acutely increase serum triglycerides. Ninety minutes after treatment of male rats with human TNF (25 micrograms/200 g, i.v.), serum triglycerides rose 2.2-fold but there was no decrease in LPL activity in epididymal fat. Sixteen hours after TNF treatment LPL activity had decreased by 44% in epididymal fat, consistent with the previously reported data. In contrast, in female rats, no significant decrease was seen in LPL activity in parametrial adipose tissue at either 90 min or 16 hr after TNF administration despite increases in serum triglycerides (1.8-fold and 1.5-fold, respectively). There was little change in LPL activity in most other adipose tissue sites of male or female rats at either time after TNF treatment. No effect of TNF was seen on heart or diaphragm muscle LPL at any time. TNF treatment of both male and female rats produces consistent increases in de novo hepatic lipogenesis in vivo under conditions that increase serum triglycerides. It is unlikely that the limited effects of TNF on LPL in vivo can account for the rapid and sustained increase in serum triglycerides.

Adipose Tissue↗
PubMed1988

Carbohydrate feeding increases total body and specific tissue 3,5,3'-triiodothyronine neogenesis in the rat.

The glucose-fed rat, in contrast to the chow-fed animal, has a higher serum total T3 concentration and an increase in the hepatic content of T4 5'-deiodinase (type I) activity. The mechanism and significance of these glucose-induced changes in T3 metabolism are elucidated in this study. To focus on extrathyroidal thyroid hormone metabolism the kinetic parameters were determined in thyroidectomized T4-replaced rats (1.25 micrograms T4/100 g BW.day). Kinetics of T4 and T3 were studied separately by infusing labeled hormone to equilibrium. Glucose feeding for 72 h (G) significantly increased both the total and free serum T3 concentrations compared to the respective means in the chow-fed control group (P). The glucose-induced changes in serum T3 reflect the approximate doubling of T3 production to 14.7 +/- 0.6 ng/h.100 g in G rats compared to 7.6 +/- 0.7 ng/h.100 g in P rats. The higher T3 production rate in the G group is due to a significant increase in the fractional total body T4 to T3 conversion (0.33 +/- 0.02) compared to that in the P group (0.19 +/- 0.02). The tissue (liver, kidney, brain, and brown adipose tissue) concentration of T4 (nanograms per g wet wt) was significantly increased in the G group. The increase ranged from 54% in liver to 80% in kidney, brain, and brown adipose tissue. The tissue concentration of T3 (nanograms per g wet wt) was even more dramatically increased by glucose feeding than was T4. The glucose-induced increment in organ T3 ranged from 2.5-fold (kidney, muscle, and brain) to 5-fold (liver and white adipose tissue) to 12-fold (brown adipose tissue). These data indicate that the increase in serum total and free T3 concentrations associated with glucose feeding reflects augmented total body T3 production from T4. The effect of the enhanced T3 neogenesis was generalized, as the T3 content was increased in each organ studied. Thus, glucose feeding has unique effects on T3 metabolism.

Adipose Tissue↗
PubMed1988

Reverse T3 and modulators of the calcium messenger system rapidly decrease T4-5'-deiodinase II activity in cultured mouse neuroblastoma cells.

Neural T3 neogenesis is modulated by the enzyme T4-5'-deiodinase type II (T4-5'-DII). Hypothyroidism increases the activity of rat pituitary and cerebral cortex enzyme activity. Mouse neuroblastoma cells (NB41A3) incubated in thyroid hormone deficient medium also show a significant increase in T4-5'-DII activity. This response is rapidly (less than 30 minutes) reversed by reverse T3 (rT3) suggesting a mechanism independent of nuclear T3 receptor binding or new protein synthesis. This report details a series of studies performed to elucidate the nature of this rT3 effect. Confluent neuroblastoma cell culture preparations maintained in hypothyroid medium showed a 2-3 fold increase in T4-5'-DII activity compared to preparations in standard medium (p less than 0.001). RT3 (1-50 nM), the calcium ionophore A23187 (0.3-1.5 microM) and the phorbol ester TPA (0.1-1.0 microM) reversed the effect of thyroid hormone deficient medium on enzyme activity (p less than 0.001). Each agent showed a similar time course with maximal effect occurring between 15-30 minutes post medium supplementation. The suppressive effect of A23187 (1.5 microM) and TPA (0.5 microM) on enzyme activity was not additive. In addition, the combination o of rT3 (50 nM) and A23187 (1.5 nM) did not decrease enzyme activity compared to each agent alone. In contrast, the combined addition of rT3 (50 nM) and TPA (0.5 microM) did have an additive effect on neuroblastoma T4-5'-DII activity. A similar pattern of response was found, when the effects of these agents were analyzed on T4-5'-DII activity in neuroblastoma cells incubated in N-FSC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

The diagnostic dilemmas of hyperthyroxinemia and hypothyroxinemia.

It should be apparent that the diagnosis of thyrotoxicosis and hypothyroidism can be correctly made in the majority of ambulatory patients. However, the clinician needs to be extremely careful in reaching such a definitive diagnosis on the hospitalized patient. Both the clinical features and the standard thyroid function tests need careful evaluation and reanalysis before the diagnosis of thyroid dysfunction can be made with confidence.

Humans↗
PubMed1987

Brain lipoprotein lipase is responsive to nutritional and hormonal modulation.

Functional lipoprotein lipase activity was recently described in rat brain. The present study was performed to further characterize the biologic significance of brain lipoprotein lipase (heparin releasable component) and elucidate regulatory factors. Comparative studies were performed on tissue (brain, adipose, and heart) heparin releasable lipoprotein lipase in the fasted and diabetic (streptozotocin 100 mg/kg BW IP) rat. Both fasting (96 hours) and diabetes (ten days) significantly decreased brain (cortical) (P less than .05) and adipose (epididymal fat pad) (P less than .001) lipoprotein lipase activity. In contrast, heart muscle enzyme activity was significantly increased (P less than .001) in response to fasting and diabetes. Refeeding (Purina chow 96 hours) and insulin replacement (96 hours) reversed these changes in tissue lipoprotein lipase consequent to fasting and diabetes, respectively. There was a positive correlation between the changes in serum insulin concentration and adipose lipoprotein lipase, but there was no correlation between this parameter and brain or heart lipoprotein lipase. In addition, although T3 therapy normalized the low T3 state associated with both fasting and diabetes, it had no effect on the enzyme activity in the studied tissues. However, subsequent studies demonstrated that hypothyroidism (2 weeks post thyroidectomy) significantly decreased brain lipoprotein lipase activity (P less than .001) and increased both the adipose (P less than .025) and heart (P less than .025) enzyme activity. T3 replacement (0.8 micrograms/100 BW/d for 1 week) reversed the effects of hypothyroidism. However, the relationship between brain enzyme activity and serum T3 was nonlinear as hyperthyroidism tended to reduce brain LPL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Glucose and insulin reverse the effects of fasting on 3,5,3'-triiodothyronine neogenesis in primary cultures of rat hepatocytes.

The cellular mechanisms by which carbohydrate refeeding reverses the effect of fasting on T3 metabolism were studied in primary cultures of hepatocytes (24 h) harvested from 48-h fasted rats. Net T3 neogenesis (T3 generated from T4) in the fasted hepatocyte preparations (9.2 +/- 0.9 pmol/min X 100 mg protein) was significantly less (P less than 0.001) than that in hepatocyte cultures derived from 72-h glucose-fed rats (41 +/- 0.8 pmol/min X 100 mg protein). Preincubation (18 h) with either glucose (2.5-10 mM) or insulin (10-500 nM) significantly increased the fasted hepatocyte T3 levels to 28 +/- 0.6 and 22 +/- 1.3 pmol/min X 100 mg protein, respectively. Furthermore, incubation with both of these agents demonstrated a greater effect on hepatic T3 neogenesis than with either alone. Fasted hepatocyte T3 neogenesis was enhanced by enrichment with dithiothreitol (5 mM), but the T3 generation remained significantly less than that in cells exposed to glucose or insulin. Studies with glucose analogs demonstrated that preincubation with 2-deoxyglucose (5 mM) significantly increased (P less than 0.001) hepatocyte T3 neogenesis, but 3-O-methylglucose (5 mM) had no effect. In contrast, the insulin-mimetic compounds Concanavalin-A or spermine did not stimulate T3 neogenesis in the fasted hepatocyte cultures. Thus, rat hepatocytes sustained in primary culture for 24 h retain the T3 metabolic characteristics of the intact animal. Glucose and insulin reverse the effect of fasting on hepatocyte T3 neogenesis. The additive response to glucose and insulin suggests that T3 neogenesis is modulated through different mechanisms. The replication of the glucose effect by 2-deoxyglucose and the inability of dithiothreitol to reverse the effect of fasting on hepatocyte T4 5'-deiodinase activity suggest that neither intermediates in the glycolytic pathway nor thiol cofactors mediate the glucose effect. Thus, the restoration of liver T3 metabolism consequent to carbohydrate refeeding of the fasted rat may be mediated by the glucose and insulin responses.

3-O-Methylglucose↗
PubMed1986

Thyroid hormone deiodinases in purified primary glial cell cultures.

Iodothyronine metabolism was studied in neuroglial cells prepared from neonatal rat cerebri. Astrocytes account for nearly all of the deiodinase activity in mixed glial cell cultures. The predominant pathway is 5-deiodination, which closely resembles the enzyme activity in homogenates of cerebral cortex. Astrocytes cultured in serum-free chemically defined medium show a gradual decrease in 5-deiodination and an increase in 5'-deiodination. Exposure of cells to triiodothyronine partially reverses these changes. Thus, astrocytes contain enzymes for both major deiodinative pathways and may play a role in the regulation of thyroid hormone levels in the brain.

Animals↗
PubMed1986

Iodothyronine deiodination in the brain of diabetic rats: influence of thyroid status.

Experimental diabetes causes profound alterations in the metabolism of thyroxine (T4), including a decrease in hepatic triiodothyronine (T3) generation from T4 via 5'-deiodination (5'-D). Because 5'-D in brain differs markedly from that in liver, both in enzymatic mechanism and in the response to hypothyroidism, we studied iodothyronine deiodination, in particular T4 to T3 conversion (T4-T3), by incubating 125I T4 with particulate fractions of cerebral cortex (Cx) and cerebellum (Cm) from rats made diabetic by injection of streptozotocin. In nondiabetic thyroidectomized (Tx) rats Cx and Cm T4-T3 activity was increased approximately ten-fold and two-fold, respectively, compared with intact controls. Diabetic Tx rats did not differ from nondiabetic Tx rats in the rate of net T3 production from T4 but the formation of 3,3'-T2 was slightly reduced. Insulin-treated diabetic-Tx rats showed a pattern of T4 metabolism in Cx and Cm virtually identical to that of nondiabetic Tx rats. The rate of T3 degradation, determined in parallel incubations of Cx and Cm with 125I T3, did not differ significantly among the groups, indicating that the observed differences in net T3 production were due to changes in T4 5'-D activity. Intact diabetic rats compared to nondiabetic controls showed no significant changes in T4-T3 either in Cx or in Cm. Administration of T3, 0.8 microgram per 100 g bw per day for 6 days, by constant infusion to intact rats raised T4-T3 in Cx and Cm to levels found in Tx rats. Treatment of intact diabetics with T3 caused qualitatively similar changes, i.e., a hypothyroid response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells.

The effect of a variety of cytokines on lipid metabolism in 3T3 L1 mouse fibroblasts and adipocytes was studied. Uptake of [3H]acetate by adipocytes and heparin-releasable lipoprotein lipase activity was inhibited after treatments of the cells with picomolar concentrations of recombinant human tumor necrosis factor alpha (rHuTNF-alpha), human tumor necrosis factor beta (rHuTNF-beta, also called lymphotoxin), murine interferon-gamma (rMuIFN-gamma), and a human hybrid interferon-alpha [rHuIFN-alpha 2/alpha 1 (Bgl II)]. Recombinant human interferon-gamma (rHuIFN-gamma), natural human colony-stimulating factor (HuCSF), and human interleukin 2 (HuIL-2) had no effect. Similar though less-marked suppression of [3H]acetate uptake by cytokines was seen in 3T3 L1 fibroblasts. Cytokines inhibited the incorporation of [3H]acetate into both membrane and storage lipids in the adipocytes. In addition to blocking lipid uptake and synthesis, rHuTNF-alpha and -beta, and rMuIFN-gamma stimulated the release of free fatty acid into the medium from adipocytes. Binding studies suggest that rHuTNF-alpha and rHuTNF-beta compete for the same cell-surface receptor on 3T3 L1 adipocytes, while rMuIFN-gamma binds to a separate receptor. The binding of rTNF-alpha to both adipocytes and fibroblasts can be significantly enhanced by preexposure of the cells to rMuIFN-gamma. There appear to be both high- and low-affinity receptors for rHuTNF-alpha on adipocytes, whereas fibroblasts exhibit a single class of high-affinity receptors. These results suggest that a variety of structurally distinct cytokines possess lipid mobilization activity, which may be of critical importance to the host in defense against infection or malignancy.

Acetates↗
PubMed1985

Modulation of adipose lipoprotein lipase by thyroid hormone and diabetes. The significance of the low T3 state.

The present study was performed to assess the potential relationship between the low T3 syndrome and hypothyroidism. Comparative studies were performed on the relative effects of diabetes and insulin on heparin-releasable adipose lipoprotein lipase (LPL) in the intact and hypothyroid rat. Hypothyroidism for 10 days (Tx) significantly increased adipose LPL activity (5.8 +/- 0.2 mu eq/g/h) compared with the activity (3.6 +/- 0.4 mu eq/g/h) in the normal group. Diabetes for 72 h (streptozocin, STZ, 10 mg/100 g body wt, i.p.) significantly reduced (P less than 0.005) adipose LPL activity in the Tx model. However, despite the suppressant effect of diabetes (43 +/- 11%), the enzyme activity remained equivalent to the normal group. Insulin stimulated adipose LPL in the Tx-diabetic group. The enzyme demonstrated a synergistic response to insulin and hypothyroidism. Subsequent studies were performed in the intact diabetic rat, a low T3 state. Adipose LPL activity was reduced to a similar degree by diabetes (79 +/- 2%) irrespective of the serum T3 concentration. Furthermore, the magnitude of the adipose LPL stimulation by insulin was not modulated by the endogenous serum T3. However, co-treatment of the diabetic group with T3 and insulin blunted the adipose LPL response to insulin. These various modulations in adipose LPL activity were associated with significant but opposite changes in serum triglyceride levels in both the hypothyroid and intact rat. These studies demonstrate that hypothyroidism counteracts the suppressant effect of diabetes on heparin-releasable rat adipose LPL activity and magnifies the enzyme response to insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1983

Somatostatin inhibits rat hepatic T4-5'-deiodinase. The effect is independent of the associated hypoinsulinemia.

Somatostatin decreases the serum 3,5,3'-triiodothyronine (T3) concentration in athyreotic subjects treated with L-thyroxine (T4). The present study was performed to determine the effect of somatostatin on T4-5'-deiodinase activity in rat tissue homogenate preparations. This enzyme is an important regulator of T3 production. Continuous somatostatin infusion at high dose (4 micrograms/kg per min subcutaneously) and low dose (0.8 micrograms/kg per min subcutaneously) for 48-72 h significantly increased (P less than 0.001) the mean aorta plasma somatostatin-like immunoreactivity concentration to 786 +/- 65 and 448 +/- 58 pg/ml, respectively compared with the normal mean of 69 +/- 17 pg/ml in the carbohydrate-fed rat (20% glucose in water ad lib.). The mean hepatic T4-5'-deiodinase activity at both 48 h (100 +/- 5 pmol/min per 100 mg protein) and 72 h (90 +/- 7 pmol/min per 100 mg protein) was significantly reduced in the high-dose group (P less than 0.005), compared with the mean enzyme activity in the glucose-fed control group (138 +/- 6 pmol/min per 100 mg protein). There was a negative correlation (r = -0.9, P less than 0.01) between the alterations in the peripheral plasma somatostatin-like immunoreactivity concentration and hepatic T4-5'-deiodinase activity. High-dose somatostatin did not consistently lower the serum T3 concentration in the glucose-fed rat. Somatostatin had no effect on pituitary T4-5'-deiodinase activity in the glucose-fed rat. High-dose somatostatin also significantly inhibited (P less than 0.01) the glucose-refeeding reactivation of hepatic T4-5'-deiodinase in the 72-h-fasted rat. The mean enzyme activity after 96 h was 96 +/- 8 pmol/min per 100 mg protein compared with 127 +/- 4 pmol/min per 100 mg protein in the refed control group. Somatostatin had a similar inhibitory effect on serum T3. There was a positive correlation (r = 0.5, P less than 0.01) between the somatostatin-induced alterations in serum T3 and hepatic T4-5'-deiodinase during refeeding. A significant positive correlation (r = 07, P less than 0.005) was noted between the somatostatin effect on hepatic T4-5'-deiodinase activity and the induced hypoinsulinemia in the fed group. In addition, a significant negative correlation (r = -0.9, P less than 0.001) was noted between the suppressed enzyme activity and the serum glucose/insulin ratio in the refed group. However, although low-dose somatostatin also induced the same degree of hypoinsulinemia (P less than 0.05) in the fed and refed groups it had no effect on hepatic T4-5'-deiodinase activity. Furthermore, despite the induction of hyperinsulinemia during refeeding, the high dose somatostatin inhibitory effect on enzyme activity persisted. Thus, somatostatin inhibited hepatic T4-5'-deiodinase activity in the carbohydrate-fed rat and prevented the carbohydrate-refeeding normalization of enzyme activity in the 72-h-fasted rat. The effect of somatostatin on enzyme activity was independent of the associated hypoinsulinemia. In the carbohydrate-fed animal the somatostatin effect was selective, as the hormone had no effect on pituitary T4-5'-deiodinase activity. These data suggest that somatostatin could play a role in the peripheral metabolism of thyroid hormones.

Animals↗