Search PubMed⌕ Search

Biomedical subjects

R H Eckel

Publications and source records attributed to R H Eckel.

At least 55 records · Page 3Linked to original sources
PubMed1998

Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children.

In conditions associated with insulin resistance, insulin-like growth factor binding protein-I (IGFBP-I) levels have been shown to correlate inversely with insulin levels. Puberty is associated with insulin resistance and thus provides a model for comparing the relationship of IGFBP-I to both insulin levels and measures of insulin sensitivity. Our study population consisted of 104 healthy pubertal children, age 9.8-14.6 yr. Each subject had his/her insulin sensitivity (Si) assessed by the modified minimal model of Bergman, which employs a frequently sampled i.v. glucose tolerance test. Results showed that IGFBP-I levels were significantly higher in boys than in pubertally matched girls (P < 0.01). There was a strong positive correlation between IGFBP-I levels and Si (r = 0.65, P < 0.0001) and a weaker negative correlation with fasting insulin levels (r = -0.38, P < 0.0001). An inverse relationship was also found between IGFBP-I levels and body mass index (r = -0.46, P < 0.0001) and with IGF-I levels (girls only, r = -0.41, P < 0.003). Consequently, insulin sensitivity, obesity, and IGF-I are important predictors of IGFBP-I levels in pubertal children. It is possible that insulin-mediated suppression of IGFBP-I in obese children may increase free IGF-I levels and thus contribute to somatic growth. The same mechanism may operate in pubertal children, where insulin resistance and growth acceleration occur simultaneously.

Adipose Tissue↗
PubMed1998

Alterations in cholesteryl ester transfer, lipoprotein lipase, and lipoprotein composition after combined pancreas-kidney transplantation.

IDDM patients treated with conventional subcutaneous insulin have an abnormal increase in cholesteryl ester transfer (CET), the proatherogenic step in reverse-cholesterol transport that results in the enrichment of the apolipoprotein (apo) B-containing lipoproteins (VLDL, LDL) with cholesteryl ester (CE). This disturbance is closely linked to iatrogenic hyperinsulinemia and the nonphysiologic stimulation of lipoprotein lipase (LpL), a physiologic activator of CET, because lowering systemic insulin levels by administering insulin through the intraperitoneal insulin route normalizes LpL and CET. Hyperinsulinemia persists in IDDM patients who undergo successful pancreas-kidney transplantation (PKT) when their allografts are placed in the pelvis and drain into the iliac vein. Therefore, to determine whether hyperinsulinemia promotes CET in this setting, we studied CET, LpL, and insulin levels in 14 euglycemic normolipidemic IDDM PKT patients with near-normal kidney function (creatinine 1.5 +/- 0.4 mg/dl). Consistent with our prediction, the net mass of CE transferred from HDL to VLDL + LDL was significantly increased in the PKT group (P < 0.001) compared with nondiabetic renal transplant patients receiving the same immunosuppressive drugs and healthy control subjects. Both basal and arginine-stimulated insulin levels were increased above the kidney transplant group's levels and correlated with the mass of CE transferred at 2 h (r = 0.71, P < 0.05; r = 0.66, P < 0.05, respectively). Total basal LpL activities, LpL and hepatic triacylglycerol lipase activities, and LpL mass all tended to be higher than levels in healthy control subjects. Consistent with these changes in lipase activity, VLDL particle size was significantly reduced (P < 0.025) compared with that of control subjects. These findings indicate that PKT patients with systemically draining allografts have a persisting profile of potentially atherogenic disturbances in insulin levels, LpL, and CET that resemble IDDM patients treated with conventional subcutaneous insulin injections.

Adult↗
PubMed1998

Lipoprotein lipase is expressed in cultured Schwann cells and functions in lipid synthesis and utilization.

We have previously demonstrated that lipoprotein lipase (LPL; triacylglycero-protein acylhydrolase, EC 3.1.1.34) is most likely expressed in the non-neuronal cells of the spinal cord, and glial cells may thus be the site of expression in the peripheral nervous system as well. We investigated the expression of LPL in cultured 1. 17 cells, an immortalized rat sciatic nerve Schwann cell line. The 1. 17 cells were shown to express LPL mRNA by reverse transcriptase-polymerase chain reaction analysis. The 1.17 Schwann cells demonstrated heparin-releasable lipolytic activity that was inhibited by the lipase inhibitor tetrahydrolipstatin in a dose-dependent manner. Preincubation of 1.17 cells with an anti-rat LPL antiserum reduced the heparin-releasable lipolytic activity to <10% of that measured in untreated cells. To investigate the role of LPL in Schwann cell lipid metabolism, 1.17 cells were incubated for up to 24 h with an emulsified [14C]triolein substrate and the incorporation of [14C]triolein radioactivity into various cellular lipids was examined in the presence of either anti-rat LPL antiserum or preimmune serum. Inhibiting LPL activity reduced the incorporation of 14C into cellular polar lipids, diacylglycerol, and cholesteryl esters by >80% at 2 and 6 h after addition of the radiolabeled substrate. At 24 h, radioactivity in diacylglycerol and cholesteryl esters was similar in cells treated with anti-LPL antiserum or preimmune serum, whereas 14C incorporation into polar lipids was still reduced by >60%. Separation of the polar lipids into individual lipid species revealed no specific changes in triolein-derived radioactivity incorporation across the phospholipid species examined. These results suggest that LPL-mediated hydrolysis of exogenous triacylglycerol is an important source of free fatty acids for the Schwann cell and thus may play a critical role in myelin biosynthesis in the peripheral nervous system.

Animals↗
PubMed1997

Adipose tissue-derived tumor necrosis factor-alpha activity is elevated in older rats.

High levels of adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) mRNA and protein have previously been associated with genetic models of obesity and insulin resistance. Because there are endogenous TNF inhibitors it is unknown if AT-TNF activity is also increased. We hypothesized that AT-TNF activity would increase in older animals because of an accumulation of fat mass. We chose to study 2 different-aged male Fischer 344 rats, 3-month-old (young) and 14-month-old (mature) because fat mass should be quite different but insulin action on glucose metabolism similar. Indeed, mature rats had over 1.5-fold more fat mass, but whole body insulin resistance, as estimated by fasting plasma insulin, was similar to young rats. Mature rats had twice as much AT-TNF activity as the young in both the epididymal (EPI) and retroperitoneal (Retro) fat pads (p < .0005). AT-TNF correlated with fasting plasma insulin in Retro only (r = .48, p = .04). AT-TNF activity strongly correlated with cell size in both EPI and Retro (r = .79 and .81, respectively, p < .0001). Because cytokines can be regulated at several levels, AT-TNF activity, protein, and mRNA were measured. AT-TNF protein levels were higher in young rats, suggesting that these animals may secrete an inhibitor that reduces AT-TNF activity. There were no significant differences in AT-TNF mRNA between groups. Since TNF has been shown to affect several key genes in tissue culture, mRNA for lipoprotein lipase, hormone-sensitive lipase, and Glut4 were measured. No differences were found between groups. In summary, AT-TNF activity increased in mature animals in relation to adipose cell size.

Adipocytes↗
PubMed1997

Prevention of diet-induced obesity in transgenic mice overexpressing skeletal muscle lipoprotein lipase.

Transgenic (Tg) FVB/N mice were produced that overexpress human lipoprotein lipase (LPL) in skeletal muscle using the muscle creatine kinase promoter and enhancers. It was hypothesized that, by overexpressing LPL in muscle, high fat feeding-induced obesity would be prevented by diverting lipoprotein-derived triglyceride fatty acids away from storage in adipose tissue to oxidation in muscle. Mice were examined both at 6 wk of age before high fat (HF) feeding and at 19 wk of age after 13 wk of HF (46.1% fat) or high carbohydrate (HC) feeding (11.5% fat). At 6 wk in heterozygous Tg mice, LPL was increased 11-fold in white muscle and 2.5-fold in red muscle, but not in cardiac muscle or spleen, brain, lung, kidney, or adipose tissue. Plasma triglycerides (mg/dl) were lower in Tg mice (87 +/- 7 vs. 117 +/- 7, P < 0.0001), and glucose increased (201 +/- 9 vs. 167 +/- 8 mg/dl, P = 0.029). There were no differences in body weight between Tg and nontransgenic (nTg) mice; however, carcass lipid content (% body wt) was significantly decreased in male Tg mice at 6 wk (7.5 +/- 1.0 vs. 9.0 +/- 1.0%, P = 0.035). Body composition was not different in female Tg mice at 6 wk. Overall, when Tg mice were fed either a HC or HF diet for 13 wk, plasma triglycerides (P < 0.001) and free fatty acids (P < 0.001) were decreased, whereas plasma glucose (P = 0.01) and insulin (P = 0.05) were increased compared with nTg mice. HF feeding increased carcass lipid content twofold in both male (10.3 +/- 1.1 vs. 21.4 +/- 2.6%, HC vs. HF, P < 0.001) and female nTg mice (6.7 +/- 0.9 vs. 12.9 +/- 1.8%, P = 0.01). However, the targeted overexpression of LPL in skeletal muscle prevented HF diet-induced lipid accumulation in both Tg male (10.2 +/- 0.7 vs. 13.5 +/- 2.2%, HC vs. HF, P = NS) and female Tg mice (6.8 +/- 0.6 vs. 10.1 +/- 1.4%, P = NS). The potential to increase LPL activity in muscle by gene or drug delivery may prove to be an effective tool in preventing and/or treating obesity in humans.

Animal Feed↗
PubMed1997

High fat diets elevate adipose tissue-derived tumor necrosis factor-alpha activity.

Adipose tissue-derived tumor necrosis factor-alpha (AT-TNF) has been associated with genetic models of insulin resistance and obesity. It is presently unknown if secreted AT-TNF protein is bioactive or whether it can be increased by environmentally induced obesity. In this study, male Wistar rats were fed either a low fat (LF; 12% of energy from corn oil) or a high fat (HF; 45% of energy from corn oil) diet for 5 weeks. From previous data, it is known that after 3 weeks, HF fed animals are obese and insulin resistant compared with the LF group. Hence, animals were killed at 1 week of HF feeding, during the acute response to the diet, and at 5 weeks, when differences in body fat are manifest. Weight gain was significantly increased by diet (P = 0.03) and time (P < 0.0001). AT-TNF bioactivity was measured on secreted protein collected from medium of minced, incubated epididymal (EPI), mesenteric (MES), and retroperitoneal (RETRO) fat pads. AT-TNF bioactivity was significantly increased by diet (P = 0.003) in the RETRO pad and tended to increase (P = 0.07) in EPI. AT-TNF activity was unaffected by diet or time in the MES pad. In the RETRO pad, TNF activity correlated negatively with RETRO fat cell number (r = -0.46, P = 0.002). Secreted AT-TNF protein did not correlate with AT-TNF activity but instead decreased in RETRO with time but not diet. In EPI, secreted AT-TNF protein decreased with the HF diet. Thus, these data suggest that high fat diets and obesity can influence AT-TNF bioactivity and secretion but in an apparent fat pad-specific manner.

Adipocytes↗
PubMed1997

Isoproterenol and somatostatin decrease plasma leptin in humans: a novel mechanism regulating leptin secretion.

In cultured adipocytes, leptin is increased by insulin and decreased by cAMP. In animal models, insulin and agents that increase intracellular cAMP have been shown to similarly affect plasma leptin in vivo. This study was undertaken to test the hypothesis that in humans increased cAMP induced by isoproterenol would decrease leptin. Five groups of normal weight subjects were studied; 1) subjects infused with isoproterenol at a rate of 24 ng/kg/min (ISO24); 2) subjects infused with isoproterenol at a rate of 8 ng/kg/min (ISO8); 3) subjects infused with somatostatin/insulin/GH followed by coinfusion with 8 ng/kg/min isoproterenol (ISO8 + SRIH); 4) subjects infused with somatostatin/insulin/GH alone (SRIH); and 5) control subjects infused with saline (NS). ISO24 infusion resulted in a 27% decrease in plasma leptin over 120 min. ISO24 also increased plasma insulin over the infusion. ISO8 resulted in a 16% decrease in leptin. Saline did not change leptin. SRIH alone decreased leptin 19% over the first 120 min, however no additional fall was seen over the next 120 min the SRIH group. Nonetheless, the addition of 8 ng/kg/min ISO during the second 120 min (ISO8 + SRIH) caused a 15% further decline in plasma leptin. Therefore both isoproterenol and somatostatin reduce plasma leptin in humans. The effect of isoproterenol is likely mediated by beta-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of leptin.

Adrenergic beta-Agonists↗
PubMed1997

Effects of multiple daily insulin injections and intraperitoneal insulin therapy on cholesteryl ester transfer and lipoprotein lipase activities in NIDDM.

Although the relationship between the actions of cholesteryl ester transfer protein (CETP) and atherosclerosis is complex, a strong body of evidence suggests that its activity (cholesteryl ester transfer [CET]) is proatherogenic. We have previously shown that CET is increased in IDDM patients receiving conventional subcutaneous insulin treatment and normalized when systemic insulin levels are lowered with intraperitoneal insulin delivery (IP). Since CET has been found by many observers to also be accelerated in NIDDM, we sought to determine whether the same salutary effect could be achieved in insulin-requiring NIDDM men before and 7 months after randomization to an intensive treatment regimen (Rx) of either IP (n = 9) or multiple daily insulin injections (MDI; n = 13). HbA1c improved to the same degree in both groups (MDI group: 9.4 +/- 1.1% pre-Rx vs. 7.2 +/- 0.7% post-Rx [P < 0.001]; IP group: 9.2 +/- 1.3% pre-Rx vs. 7.1 +/- 0.5% post-Rx [P < 0.001]). Compared with pre-Rx levels, plasma triglycerides were not significantly changed by either treatment (MDI group: 136 +/- 80 mg/dl pre-Rx vs. 139 +/- 87 mg/dl post-Rx; IP group: 157 +/- 63 mg/dl pre-Rx vs. 188 +/- 89 mg/dl post-Rx), though an upward trend followed IP. Before randomization, CET estimated with both mass and isotopic assays was greater in the NIDDM subjects than in nondiabetic control subjects (P < 0.001). With improved glycemic control, CE mass transfer declined in both groups, but only reached normal levels in the IP group (MDI group at 2 h: 49.0 +/- 13.7 [mean +/- SD] pg pre-Rx vs. 29.5 +/- 15.3 microg post-Rx [-39.7%, P < 0.01]; IP group at 2 h: 40.8 +/- 23.3 microg pre-Rx vs. 10.9 +/- 6.5 microg post-Rx [-73.2%, P < 0.05]) and remained abnormally increased (P < 0.005) in the subjects receiving MDI. Total lipolytic activity after intensive treatment was unchanged from pretreatment levels, which were similar to those of the reference group. Although directional changes in lipoprotein lipase (LpL) and hepatic triglyceride lipase (HTGL) similar to those found in IDDM after MDI and IP were observed, they were not statistically significant. Thus, while improved glycemic control alone achieved by either MDI or IP reduced the pathological increase in CET in these insulin-treated NIDDM men, normalization was only achieved in those treated with IP. Despite near-normal HbA1c levels, CET remained abnormally increased in NIDDM patients treated rigorously with conventional subcutaneous insulin delivery.

Adult↗
PubMed1996

Periprandial systemic and regional lipase activity in normal humans.

An assay for plasma lipoprotein lipase activity was used without prior injection of heparin to study arteriovenous differences of lipases across skeletal muscle and adipose tissue of normal male volunteers. Lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities and triglyceride?concentrations were measured in arterial plasma and in venous effluent plasma from forearm skeletal muscle and subcutaneous abdominal adipose tissue, in the postabsorptive state and after a mixed meal. Triglyceride clearance by the tissues was greater across adipose tissue than across muscle. There were no arteriovenous differences for HTGL activity. In the postabsorptive state skeletal muscle released LPL activity, but adipose tissue did not. Postprandially the arterial LPL and HTGL activities did not change. LPL activity in adipose tissue venous effluent rose, whereas that in muscle venous effluent decreased. These results show that the release of LPL from subcutaneous adipose and forearm tissues is regulated differently, reflecting in vivo differences in LPL regulation at the tissue level.

Absorption↗
PubMed1996

Adipose-specific overexpression of GLUT-4 in transgenic mice alters lipoprotein lipase activity.

Transgenic mice overexpressing GLUT-4 selectively in adipose tissue using the aP2 promoter/enhancer develop obesity, enhanced glucose tolerance, and increased insulin sensitivity. The current study was designed to determine whether altering glucose transport affects lipoprotein lipase (LPL) activity. Female transgenic mice (10-12 mo old) have increased parametrial fat pad weight, adipocyte size, total body lipid and fasting plasma triglycerides, fatty acids, and glycerol compared with nontransgenics. Stimulation of LPL activity by feeding is blunted in parametrial and perirenal fat from 15- and 22-fold in nontransgenic mice to three- to sevenfold in transgenics. LPL activity in the fed state in transgenic mice is reduced 60-75% in fat. In heart and skeletal muscle of transgenic mice, LPL activity in the fasted state is 55-65% lower than in nontransgenics and feeding induces an unexpected rise in LPL activity. Muscle LPL activity is strongly and inversely correlated with glucose transport in adipocytes (r = -0.942, P < 0.005), which is increased 15- to 27-fold in the basal state and 4.5- to 6.9-fold in the insulin-stimulated state in transgenics. Whereas stimulation of adipose LPL may be blunted by lower plasma insulin levels in transgenics, fasting muscle LPL may be suppressed by elevated plasma lipids. Thus altering the partitioning of glucose between adipose tissue and muscle alters a critical step for the partitioning of lipoprotein fatty acids between these tissues.

Adipose Tissue↗
PubMed1996

Tissue-specific regulation of lipoprotein lipase by isoproterenol in normal-weight humans.

Lipoprotein lipase (LPL) is a hydrolytic enzyme, involved in lipoprotein metabolism and nutrient partitioning, that is subject to tissue-specific regulation. Evidence for divergent regulation of the lipase by insulin has been demonstrated, but alterations in the tissue-specific response of LPL to catecholamines has not been studied in humans. The regulation of LPL in gluteal adipose tissue and vastus lateralis muscle by isoproterenol (epinephrine isopropyl homologue) in humans was examined over 2 h in subjects infused with 0 (saline) or 8 or 24 ng.kg-1.min-1 isoproterenol. The infusion of normal saline into control subjects failed to alter adipose tissue or skeletal muscle LPL activity. However, in the saline-infused subjects there was a positive correlation between the percent change in plasma norepinephrine concentrations and the percent change in muscle LPL activity (r = 0.826, P < 0.05). Isoproterenol infusion did not change LPL in either adipose tissue or muscle compared with saline-infused controls, but plasma insulin levels in addition to plasma glucose, free fatty acids, and glycerol were increased. To prevent the isoproterenol-induced hyperinsulinemia, a pancreatic clamp technique was utilized. An increase in muscle LPL was demonstrated (P = 0.037) with no change in adipose tissue LPL. The change in muscle LPL activity after the 2-h infusion correlated with the change in muscle mRNA (P = 0.021). Overall, these studies indicate that in humans the response of LPL to catecholamines is tissue specific with no effect in adipose tissue but a stimulation in skeletal muscle. Endogenous regulation of LPL in muscle by catecholamines could be important in muscle fuel metabolism and could relate to effects of adenosine 3',5'-cyclic monophosphate and/or fatty acids at the level of the LPL gene.

Adipose Tissue↗
PubMed1995

Dietary fat is shunted away from oxidation, toward storage in obese Zucker rats.

Previous measurements of lipoprotein lipase (LPL) activity in adipose tissue (ATLPL) of lean and obese Zucker rats have consistently documented increased activity in obese rats relative to lean. Since LPL is considered to be rate limiting for the delivery of triglyceride fatty acids (TGFA) to muscle and adipose tissue, these data have been used to suggest that the metabolic partitioning of TGFA favors storage over oxidation in obese rats. To document the partitioning of TGFA directly, the fate of 14C labeled oleic acid (42nmols) was fed to lean, obese, and obese Zucker rats fed a hypocaloric diet designed to chronically reduce weight 25% below that of obese controls (reduced-obese). The amount of 14C recovered in CO2 over 6 hours following ingestion was significantly less in obese rats compared to lean (0.45 +/- 0.06 vs. 0.88 +/- 0.09nmols, p = .0004) and less still in the reduced obese group (0.34 +/- 0.06nmols p = .00003). Six hours after ingestion, the quantity of label found in adipose tissue was significantly greater in the obese rats compared to lean (14.51 +/- 1.92 vs. 1.38 +/- 0.29nmols p < .00001), but was intermediate in the reduced-obese group (9.23 +/- 0.98nmols p = .0003). At 2.2 hours there was significantly more label in skeletal muscle of lean rats compared to either obese or reduced-obese (2.33 +/- 0.24; 1.35 +/- 0.04nmols p = .01; 1.41 +/- 0.27nm p = .02). However, at 6 hours these differences between groups were no longer present. These finding Indicate that dietary fat is shunted away from oxidation toward storage in obese Zucker rats. Additionally it appears that there may be a relative block in the oxidation of TGFA that is taken up by skeletal muscle in obese rats. Finally the relative normalization of this partitioning defect in reduced-obese rats is at variance with what was suggested by previous measurements of tissue specific levels of LPL, and suggests an enhanced recirculation of fatty acids from adipose tissue to muscle in reduced-obese rats. This could occur through increased delivery of non-esterified fatty acids (NEFA) to muscle as a result of an increase in net lipolysis.

Adipose Tissue↗
PubMed1995

Trafficking of dietary fat in lean rats.

Despite increasing interest in the role that fuel partitioning plays in determining body composition, the relative importance of oxidative versus storage pathways in the clearance of dietary fat remains unclear. A widely held view is that the primary destination of chylomicron triglyceride fatty acids (TGFA) is adipose tissue, and the primary source of lipid fuel for skeletal muscle is non-esterified fatty acids (NEFA). An alternate view is that muscle, not adipose tissue, is the primary site of TGFA clearance. This view is supported by estimates of the total lipoprotein lipase content of muscle and adipose tissue. To directly study the partitioning of dietary fat between oxidation and storage, 14C-labeled oleic acid was fed to Sprague Dawley rats and its metabolic rate followed over 30 days. Two hours after ingestion, more than 3.5 times as much label was found in skeletal muscle tissue (2.42 +/- 0.45 nmols) and CO2 (0.25 +/- 0.01 nmols) than was found in adipose tissue (0.71 +/- 0.14 nmols). Intramuscular triglyceride was the lipid class most extensively labeled. After skeletal muscle, liver was the next most important site of TGFA clearance. Surprisingly a substantial quantity of label remained associated with the GI tract even 24 hours after ingestion. Between 2 and 10 days following ingestion there was a net decline in the 14C content of muscle, liver and GI tract, associated with a net rise in the 14C content of adipose tissue. These findings demonstrate: 1) the importance of skeletal muscle and liver in whole organism TGFA clearance, 2) the importance of intramuscular partitioning of lipid fuels between direct oxidation and storage as TG, 3) the potentially important role of the GI tract in the delivery of dietary fat to the circulation 10-24 hours following ingestion, and 4) the stability of adipose tissue as a storage site. The complex nature of the tissue-specific clearance of TGFA over time is perhaps better described by the term "trafficking" than by the more commonly used term "partitioning." Future studies of TGFA clearance combined with sampling of relevant tissues over time will provide insight into the specific roles that abnormalities in liver, muscle and adipose tissue TGFA metabolism play in the development of hypertriglyceridemic disorders and states of increased or reduced body weight.

Adipose Tissue↗
PubMed1995

Weight regain following sustained weight reduction is predicted by relative insulin sensitivity.

Ten moderately obese women (body mass index 34.9 +/- 1.1 kg/m2, mean +/- SEM), had previously been through a 3-month weight loss program followed by 3 months of weight maintenance at the reduced weight. A euglycemic clamp for determination of insulin sensitivity was performed on each subject prior to weight loss, and another at the end of the weight maintenance phase. The mean weight loss for the group was 11.4 +/- 2.2 kg. The women were then seen for follow-up weights 12 months and 18 months after the conclusion of the weight maintenance period. All of the women except one had regained their weight by the time of the 12-month visit. It was found that the amount of weight regained both at 12 months and 18 months was correlated with the change in insulin sensitivity which occurred from the baseline study to after weight loss/maintenance. The data indicate that increased insulin sensitivity following sustained weight loss in obese women predicts weight regain.

Adult↗
PubMed1995

Glycohemoglobin levels relate to the response of adipose tissue lipoprotein lipase to insulin/glucose in obese non-insulin-dependent diabetes mellitus.

Adipose tissue lipoprotein lipase (ATLPL) is responsible for the provision of lipoprotein-derived fatty acids to adipocytes for storage as triglycerides. Fasting ATLPL has been shown to be decreased in non-insulin-dependent diabetes mellitus (NIDDM), an insulin-resistant state. Medically uncomplicated obesity, another state of relative insulin resistance, is associated with decreased stimulation of the enzyme in response to metabolic stimuli. It was therefore hypothesized that the increased insulin resistance of NIDDM would result in an even greater defect in the response of ATLPL to insulin/glucose. Gluteal adipose tissue biopsies were performed in 13 premenopausal obese women with NIDDM, before and after 6 hours of intravenous insulin and glucose. Metabolic data from these studies were then compared with those obtained from 26 nondiabetic obese women of similar age, weight, and fasting insulin concentration (obese controls [OBC]). As expected, fasting gluteal ATLPL activity was lower in the NIDDM group than in OBC (3.7 +/- 0.9 v 11.1 +/- 1.6 nmol free fatty acids [FFA]/min/10(6) cells, P = .0003). The change in ATLPL activity (delta ATLPL) in response to a 6-hour insulin/glucose infusion was not statistically different between the two groups (2.2 +/- 1.1 v 4.7 +/- 1.2, P = .114). However, in NIDDM subjects there was a strong positive relationship between delta ATLPL and glycohemoglobin (GHb) level (r = .883, P = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1995

Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus.

Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myocytes for lipoprotein triglyceride oxidation. In human obesity, an insulin-resistant state, SMLPL levels measured in the fasted state are either decreased or unchanged as compared with levels in normal-weight controls. However, insulin/glucose infusion increases SMLPL activity in obese individuals, whereas in normal-weight subjects the activity is decreased. One of the goals of this study was to determine the impact of obesity with concomitant non-insulin-dependent diabetes mellitus (NIDDM) on fasting SMLPL and on the change in SMLPL activity (delta MLPL) in response to an insulin/glucose infusion. Because NIDDM is often a more insulin-resistant state, it was hypothesized that SMLPL activity would be further increased by insulin/glucose in subjects who were obese and had NIDDM. Measurements of SMLPL were made from biopsies of vastus lateralis skeletal muscle taken before and after a 6-hour insulin/glucose infusion in the setting of a euglycemic clamp. Thirteen nondiabetic obese women (OBC) and six nondiabetic normal-weight women (NWC) were used as control subjects. SMLPL levels measured in the fasted state were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calculation of the mean glucose infusion rate (GIR) required to sustain euglycemia over the last 60 minutes of the infusion. For all three groups combined, representing a continuum of insulin sensitivity, there was a positive correlation between GIR and fasting SMLPL. As described earlier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after insulin/glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗