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B C Hansen

Publications and source records attributed to B C Hansen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Age-related adipose tissue mRNA expression of ADD1/SREBP1, PPARgamma, lipoprotein lipase, and GLUT4 glucose transporter in rhesus monkeys.

Aging has been shown to have an effect on the capacity to differentiate preadipocytes and on the expression of some genes expressed in adipose tissue. The mRNA levels of adipocyte differentiation-related genes were examined in rhesus monkeys (Macaca Mulatta) ranging in age from 7 to 30 years. The effect of aging on the expression of peroxisome proliferator activated receptor gamma (PPARgamma), adipocyte determination- and differentiation-dependent factor 1/sterol regulatory element binding protein 1 (ADD1/SREBP1), CCAAT/enhancer binding protein alpha (C/EBPalpha), lipoprotein lipase (LPL), GLUT4 glucose transporter, and adipsin were examined by slot blot analysis. Significant inverse correlations were observed between age and the mRNA levels of PPARgamma, ADD1/SREBP1, LPL, and GLUT4. The coordinate downregulation of these genes may be linked to the declining fat mass of senescent animals. There was no correlation between age and the mRNA levels of adipsin. The mRNA levels of these genes were not correlated to body weight orfasting plasma insulin. These findings indicate that aging may have an effect on the adipocyte differentiation program and this effect appears to be gene specific.

Adipocytes↗
PubMed1999

Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality.

Long term chronic calorie restriction (CR) of adult nonhuman primates significantly reduces morbidity and increases median age of death. The present review is focused upon an ongoing study of sustained adult-onset calorie restriction, which has been underway for 15 years. Monkeys, initially calorie restricted at about 10 years of age, are now approximately 25 years old. The median life span of these restricted monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys. In our laboratory, maximum life span for AL-fed monkeys appears to be about 40 years. Thus, whether CR can also increase maximal life span, as it does in rodents, cannot be determined for at least another 15 years. The earliest detectable positive benefit on morbidity in these monkeys was previously reported as the prevention of obesity. Current evidence, as reviewed here, suggests that much obesity-associated morbidity is also mitigated by sustained calorie restraint in nonhuman primates. Furthermore, probably because of the prevention of obesity, diabetes has also been prevented. Recent findings include the identification of extraordinary changes in the glycogen synthesis pathway, and on the phosphorylation of glycogen synthase in response to insulin. This calorie restriction-induced prevention of morbidity does not require excessive leanness, but is clearly present when body fat is within the normal range of 10 to 22%, and this is likely to be true in humans as well.

Animals↗
PubMed1998

Monkey leptin receptor mRNA: sequence, tissue distribution, and mRNA expression in the adipose tissue of normal, hyperinsulinemic, and type 2 diabetic rhesus monkeys.

OBJECTIVE: We have cloned the rhesus monkey leptin receptor and examined its mRNA expression levels in the adipose tissue of monkeys to investigate the regulation of gene expression of the leptin receptor. RESEARCH METHODS AND PROCEDURES: Monkey leptin receptor cDNA was cloned by reverse transcriptase-polymerase chain reaction (RT-PCR). Tissue distribution of monkey leptin receptor was examined by Northern blot analysis and RT-PCR. The mRNA levels of monkey leptin receptor in adipose tissue of normal (n=10), hyperinsulinemic obese (n=8), and type 2 diabetic monkeys (n=8) were measured by quantitative RT-PCR. RESULTS: Monkey leptin receptor cDNA had at least two alternatively spliced isoforms (long and short forms). The long form of the leptin receptor mRNA was expressed relatively highly in liver, adipose tissue, hypothalamus, and choroid plexus, whereas the total leptin receptors were expressed in every tissue examined. The mRNA levels of the long form of the leptin receptor in adipose tissue were not correlated to body weight, fasting plasma insulin, plasma glucose, or plasma leptin levels. The mRNA levels of the long form of the leptin receptor were highly correlated to that of the total leptin receptor (long and short form). DISCUSSION: The long form of leptin receptor mRNA existed in adipose tissue as well as in liver and hypothalamus, suggesting that the leptin receptor in adipose tissue may be functional in adipose tissue. The expression of the leptin receptor mRNA in adipose tissue is not affected by obesity, hyperinsulinemia, or diabetes.

Adipose Tissue↗
PubMed1998

Relationships of PPARgamma and PPARgamma2 mRNA levels to obesity, diabetes and hyperinsulinaemia in rhesus monkeys.

OBJECTIVE: To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) together with CCAAT/enhancer binding protein alpha (C/EBPalpha), lipoprotein lipase (LPL) and glucose transporter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation to obesity. DESIGN: Cloning of the PPARgamma1 and gamma2 cDNAs and analysis of PPARgamma, C/EBPalpha, LPL and GLUT4 mRNA levels in the adipose tissue of lean and obese monkeys. SUBJECTS: 28 rhesus monkeys (Macaca mulatta) with a wide range of body weights (9.2-22.6 kg) and with or without type 2 diabetes. MEASUREMENTS: Sequence of PPARgamma1 and gamma2. Tissue distribution of PPARgamma1 and gamma2. The mRNA levels of PPARgamma, C/EBPalpha, LPL and GLUT4 in adipose tissue. The ratio of PPARgamma2 mRNA to total PPARgamma mRNA. RESULTS: The monkey PPARgamma2 protein showed 99% identity with the human protein. PPARgamma1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPARgamma2 existed mainly in adipose tissue. A significant correlation between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and obesity was observed, whereas total PPARgamma mRNA levels showed no significant relationships to obesity. There was also a significant relationship between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and fasting plasma insulin concentration. The mRNA levels of C/EBPalpha, LPL and GLUT4 were highly correlated to that of total PPARgamma mRNA. They were also significantly correlated to the mRNA levels of PPARgamma1 and PPARgamma2. CONCLUSIONS: The ratio of PPARgamma2 mRNA to total PPARgamma mRNA is related to obesity in the rhesus monkey and mRNA expression of PPARgamma1, PPARgamma2, C/EBPalpha, LPL and GLUT4 appear to be coordinated in vivo.

Adipose Tissue↗
PubMed1998

Insulin unexpectedly increases the glucose 6-phosphate Ka of skeletal muscle glycogen synthase in calorie-restricted monkeys.

In skeletal muscle of normal subjects, the concentration of glucose 6-phosphate (G6P) at which the activity of glycogen synthase (GS) is half maximal (Ka) is decreased by in vivo insulin, and the fractional activity is increased without a change in GS maximal activity (Vmax). We have shown that moderate chronic calorie restriction, previously shown in rodents to be effective in slowing aging, resulted in the prevention of obesity and type 2 diabetes in primates (rhesus monkeys, Macaca mulatta). However, unexpectedly, in a subgroup of calorie-restricted monkeys, insulin during a euglycemic hyperinsulinemic clamp caused an unanticipated decrease in skeletal muscle GS fractional activity. These same monkeys had the lowest whole-body glucose disposal rate (M), the greatest increase in skeletal muscle G6P content and the greatest increase in skeletal muscle glycogen phosphorylase activity during the euglycemic hyperinsulinemic clamp compared to the remaining calorie-restricted monkeys with normal insulin action. To determine whether this highly unusual insulin-mediated decrease in GS fractional activity was due to increased phosphorylation (increased Ka), we measured the activity of skeletal muscle GS at 9 different G6P concentrations before and during the euglycemic hyperinsulinemic clamp in 6 calorie-restricted monkeys. G6P Ka increased (n = 4) and Vmax decreased (n = 5) during the clamp. Basal G6P Ka was inversely related to basal GSfv (r = -0.94, p < 0.002). G6P Ka and skeletal muscle G6P content were positively related under insulin-stimulated conditions (r = 0.93, p < 0.005). The change in G6P Ka (insulin-stimulated minus basal) was inversely related to M (r = -0.94, p < 0.002) and positively related to the change in skeletal muscle G6P content (r = 0.93, p < 0.005). We conclude that moderate calorie restriction results in a reversal of normal insulin action at the skeletal muscle with inactivation of glycogen synthase which is likely to be due to an increase in phosphorylation of GS together with a decrease in Vmax of GS during a euglycemic hyperinsulinemic clamp in most of the calorie-restricted monkeys. These alterations are likely to be involved in the anti-diabetogenic effects of calorie restriction.

Animals↗
PubMed1998

Macrophages and pancreatic islet amyloidosis.

Islet amyloid formed from islet amyloid polypeptide (IAPP, amylin) is found in spontaneously diabetic monkeys and cats. Islet amyloidosis is progressive, apparently irreversible and is associated with destruction of insulin-secreting cells. The role of macrophages in the destruction and removal of islet amyloid is unknown. Therefore, the presence and morphology of macrophages were determined by electron and quantitative light microscopy in islets of diabetic and nondiabetic man and monkeys and in transgenic mice expressing the gene for human IAPP. Tissue macrophages were present in all pancreatic sections and tissue distribution was similar in exocrine and endocrine areas. There was no difference in macrophage density in amyloidotic and amyloid-free islets in monkeys and man. Macrophage density was similar in islets of transgenic mice expressing human IAPP which do not contain amyloid in vivo but in which fibrils are formed in vitro following islet isolation compared to islets from mice expressing rat IAPP which is not amyloidogenic. IAPP amyloid fibrils were visible by electron microscopy in lysosomes of pancreatic macrophages in man, monkeys and human IAPP transgenic mice. Thus, human IAPP is internalised but inefficiently degraded by tissue macrophages. Diabetes-associated amyloidosis is not associated with visible recruitment of macrophages for removal of amyloid or islet debris.

Aged↗
PubMed1997

The beta3-adrenergic receptor in the obesity and diabetes prone rhesus monkey is very similar to human and contains arginine at codon 64.

The beta3-adrenergic receptor (ADRbeta3) is a seven-membrane spanning, G-protein linked receptor expressed in brown adipose tissue in rodents, and visceral adipose tissue in humans. Stimulation of the receptor by norepinephrine leads to lipolysis and thermogenesis. In rodent models of obesity and diabetes, administration of beta3-agonists results in weight loss and improved glucose tolerance. Studies indicate that the pharmacological properties of the ADRbeta3 differ markedly between rodents and humans, making generalizations of rodent studies to humans difficult. We hypothesized that the obesity and diabetes prone rhesus monkey (Macaca mulatta) would provide an excellent animal model to study the role of the ADRbeta3 in the development of obesity and diabetes as well as for assessment of the therapeutic efficacy of beta3-agonists. We sequenced the entire coding region of the rhesus ADRbeta3 gene. Like humans, the rhesus ADRbeta3 has two exons. There is 89% amino acid (aa) identity between human and rhesus compared to 82% aa identity between human and mouse. A single base deletion results in divergence of the intracellular carboxy terminus accounting for 26 of the 45 aa changes and 10 additional aa. Of the 15 rhesus monkeys studied, all were homozygous for Arg64. In humans, Arg64 (rather than Trp) is associated with increased body mass index, insulin resistance, and an earlier onset of type II diabetes mellitus. We conclude that the rhesus ADRbeta3 is more similar to the human ADRbeta3 than to the rodent ADRbeta3 suggesting that this primate model may be more appropriate for physiologic and therapeutic studies of the ADRbeta3 axis, and that Arg64 may influence susceptibility in this species to obesity, insulin resistance, and type II diabetes.

Amino Acid Sequence↗
PubMed1997

Insulin regulates liver glycogen synthase and glycogen phosphorylase activity reciprocally in rhesus monkeys.

In skeletal muscle of both humans and monkeys, the effects of in vivo insulin during a euglycemic hyperinsulinemic clamp on the enzymes and substrates of glycogen metabolism have been well established. In liver, such effects of insulin during a clamp have not been previously studied in primates. To examine insulin action at the liver, euglycemic hyperinsulinemic clamps were performed in 10 lean young adult male rhesus monkeys. Liver biopsies were obtained at three time points: basal (fasting), that is, immediately before the onset of the clamp, and during insulin infusion at 130 and 195 min. Glycogen synthase (GS), glycogen phosphorylase (GP), glucose 6-phosphate (G-6-P), and glycogen were determined at each time point, with the greatest effects observed most frequently at 195 min. Whole body insulin-mediated glucose disposal rate was related to the change in the independent activity of GS (r = 0.63, P < 0.05). Insulin increased the GS fractional activity (P < 0.005) and decreased the activity ratio of GP (P < 0.001) compared with basal. The changes in fractional activity of GS and in activity ratio of GP were inversely related (r = - 0.68, P < 0.05), G-6-P concentration was decreased during insulin stimulation compared with basal (P = 0.01). Glycogen concentration was not significantly different between the basal and insulin-stimulated time points. We conclude that insulin during a euglycemic clamp activates liver GS while inhibiting liver GP and that insulin action on liver GS is positively related to whole body insulin-mediated glucose disposal rates in lean young adult rhesus monkeys.

Animals↗
PubMed1996

Regulation of obese (ob) mRNA and plasma leptin levels in rhesus monkeys. Effects of insulin, body weight, and non-insulin-dependent diabetes mellitus.

We have cloned the rhesus monkey obese cDNA and have analyzed its expression in monkeys with a wide range of body weights (lean to very obese) and with or without non-insulin-dependent diabetes mellitus to examine the relationship of ob gene expression to obesity and non-insulin-dependent diabetes mellitus. The sequence of monkey ob protein, excluding the signal peptide, showed 91% identity with the human protein. We observed a significant correlation between the level of ob mRNA and body weight. We also found a significant relationship between ob mRNA and fasting plasma insulin concentration; however, insulin stimulation during a 100-140-min euglycemic/hyperinsulinemic clamp did not result in any changes in ob mRNA levels. Circulating levels of the ob gene product leptin were also significantly correlated with body weight. These results show that ob gene expression is related to body weight and is not acutely regulated by insulin.

Amino Acid Sequence↗
PubMed1996

Apolipoprotein E is associated with islet amyloid and other amyloidoses: implications for Alzheimer's disease.

Apolipoprotein E (ApoE) has recently been proposed as an aetiological factor of Alzheimer's disease (AD): ApoE is co-localized to amyloid plaques and neurofibrillary tangles in the brain and binds to A beta-protein in vitro. An association of ApoE epsilon 4 allele with the development of AD has been reported. Islet amyloid is formed from islet amyloid polypeptide (IAPP) in pancreatic islets of 90 per cent of patients with non-insulin-dependent diabetes mellitus (NIDDM) which, like AD, is an age-dependent pathology. The relationship of ApoE to islet amyloid and other amyloidoses is largely unknown. In this study, ApoE was localized by immunocytochemistry on pancreatic specimens from non-diabetic man, monkey, and mouse, and on amyloid-containing human tissues from pancreas, heart, brain, and intestine. All types of amyloid deposits, irrespective of the constituent peptide, site of deposition, or species, showed immunoreactivity for ApoE (ApoE-IR). Quantitative morphometry showed that similar proportions of islet amyloid were labelled for IAPP and ApoE in monkey islets. ApoE-IR was observed in pancreatic islet cells of non-diabetics. These results suggest that the association of ApoE with amyloid is non-specific for AD or to the component peptide of amyloid fibrils. If ApoE promotes amyloid formation, its synthesis in pancreatic islets could be important for the initiation or the development of pancreatic amyloid in NIDDM.

Alzheimer Disease↗
PubMed1996

Hyperleptinemia: relationship to adiposity and insulin resistance in the spontaneously obese rhesus monkey.

Plasma leptin levels in normal-weight and spontaneously obese male rhesus monkeys, and the relationships of circulating leptin to beta-cell basal secretion, glucose-stimulated responsiveness and peripheral insulin sensitivity, were determined. Basal leptin in normal lean adult monkeys averaged 6.0 +/- 1.3 ng/ml and in the obese monkeys averaged 22.6 +/- 2.9 ng/ml. In all monkeys, plasma leptin concentration was significantly related to body weight, body fat, fasting plasma insulin, acute insulin response to intravenous glucose, and peripheral insulin sensitivity but not to fasting glucose or glucose tolerance. Body fat and plasma insulin concentration were the best predictors of circulating leptin levels (R2 = 62.6%) independent of peripheral insulin sensitivity. Four of 17 obese monkeys had plasma leptin concentrations in the normal range, a finding that may be related to the heterogeneity of obesity. The close association of plasma leptin to body fat and plasma insulin (both basal and glucose-stimulated) support the possibility of a role of leptin in the link between obesity and beta-cell hypersecretion. However, the potential role of leptin in the development of peripheral insulin resistance, hyperglycemia and type 2 diabetes will require further study.

Adipose Tissue↗
PubMed1996

Nutrition Societies Presidents' Forum: future challenges and opportunities for nutrition societies in the 21st century.

The Chair introduced "Pasteur's Quadrant" as a potentially useful paradigm for modern science. Developed by Princeton's Donald E Stokes, the quadrant is two-by-two matrix that classifies knowledge as fundamental and/or applied. The Chair also noted the effect of competitive pressures, and the necessity for cooperation among nutrition societies. The Presidents of The American Society for Nutritional Sciences (ASNS), The American Society for Clinical Nutrition (ASCN), The American Society for Parenteral and Enteral Nutrition (ASPEN), and the Chair of the Institute of Food Technologist's (IFT) Nutrition Division presented their views on how societies can prepare to meet their members' upcoming needs. The Director of the Center for Food and Nutrition Policy discussed the future role of nutrition societies and how they might interact with various interest groups. The Forum, which included an opportunity for audience participation, took place soon after the February 1996 release of "Meeting the Challenge: A Research Agenda for America's Health, Safety, and Food." Published by the Executive Office of the President's Office of Science and Technology Policy, the report highlights the importance of nutrition to our nation's health.

Humans↗
PubMed1996

Altered insulin receptor messenger ribonucleic acid splicing in liver is associated with deterioration of glucose tolerance in the spontaneously obese and diabetic rhesus monkey: analysis of controversy between monkey and human studies.

There are two insulin receptor (IR) isoforms (designated type A and type B), derived from alternative splicing of exon 11 of the IR gene. Recently, we reported (Huang Z., Bodkin N.L., Ortmeyer H.K., Hansen B.C., Shuldiner A. R., 1994, J Clin Invest, 94:1289-1296) that an increase in the exon 11- (i.e. lacking exon 11) (type A) IR messenger RNA (mRNA) variant in muscle is associated with hyperinsulinemia, an early risk factor for noninsulin-dependent diabetes mellitus (NIDDM), in the spontaneously obese, diabetic rhesus monkey. To explore further the role of IR mRNA splicing in insulin resistance of NIDDM, we studied liver, another target organ that is resistant to insulin action in NIDDM. The relative amounts of the two IR mRNA-splicing variants in liver were quantitated by RT-PCR in normal, prediabetic, and diabetic (NIDDM) monkeys. The percentage of the exon 11- mRNA variant in liver (n = 24) was significantly correlated with fasting plasma glucose (r = 0.55, P < 0.01) and intravenous glucose disappearance rate (r = -0.45, P < 0.05). The exon 11- mRNA variant was increased significantly from 29.8 +/- 1.6% in monkeys with normal fasting glucose to 39.2 +/- 2.9% in monkeys with elevated fasting glucose (P < 0.01). These studies provide the first direct evidence in vivo that the relative expression of the two IR mRNA-splicing variants is altered in liver and suggest that increased expression of the exon 11- IR isoform may contribute to hepatic insulin resistance and NIDDM or may compensate for some yet unidentified defect.

Alternative Splicing↗
PubMed1996

Glycogen phosphorylase activity and glycogen concentration in muscle of normal to overtly diabetic rhesus monkeys.

The effect of insulin to increase the activity of glycogen synthase (GS) in muscle has been well documented, however, the effect of in vivo insulin to inactivate glycogen phosphorylase (GP) has not been previously shown. To determine the effects of insulin on glycogenolysis in rhesus monkeys, GP and glycogen were determined in muscle samples obtained under basal fasting and insulin-stimulated conditions during a euglycemic hyperinsulinemic clamp in a group of 27 monkeys ranging from normal to overtly diabetic (NIDDM) and compared to GS activity previously examined. The diabetic monkeys had lower basal and insulin-stimulated glycogen concentrations compared to the normal and hyperinsulinemic monkeys (p < 0.05). The response of GP activity ratio (AR) to insulin (delta) was inversely correlated to delta GS fractional velocity (fv) (r = -0.57, p < 0.002) in all of the monkeys. The AR of GP was inversely correlated to the fv of GS measured under insulin-stimulated conditions (r = -0.60, p < 0.05) in the 11 normal monkeys. In the normal group, the range in response of GS to insulin (delta GSfv) was previously shown to be 3-22%, with n = 6 < 11% ('low normals') and n = 5 > 11% ('high normals'). In the present study, the low normals were shown to have (1) higher delta GP independent activity and delta GP total activity compared to the high normals and hyperinsulinemic monkeys (p less than or equal to 0.05), (2) higher insulin-stimulated GP independent activity and GP total activity compared to the other three groups (p < 0.05), (3) higher insulin-stimulated GP activity ratio compared to the high normals and hyperinsulinemic monkeys (p < 0.05), (4) and lower whole-body insulin-mediated glucose disposal rates compared to the high normals (p < 0.05). We conclude that NIDDM is accompanied by low glycogen content in the muscle, and that some clinically normal monkeys have an alteration in insulin action on muscle GS, GP, and whole-body glucose disposal rates that may precede the development of hyperinsulinemia.

Animals↗
PubMed1995

Effects of D-chiroinositol added to a meal on plasma glucose and insulin in hyperinsulinemic rhesus monkeys.

We have previously demonstrated that D-chiroinositol, administered intravenously to insulin-resistant monkeys, increases the rate of disappearance of plasma glucose and insulin. The purpose of the present study was to determine whether orally administered D-chiroinositol might also similarly improve the postprandial plasma glucose profile of hyperinsulinemic insulin-resistant monkeys. A complete liquid diet meal (15 ml/kg body weight) was ingested by each of six monkeys on two occasions separated by 10 days, with conditions identical except D-chiroinositol (500 mg/kg body weight) was added to the second meal. At 110 minutes following each meal, the monkeys were anesthetized and blood samples obtained at 120, 150, 180, 210, 240, 270 and 300 minutes. Plasma glucose and insulin concentrations were determined. The mean plasma glucose concentration (120-300 minutes) was significantly lower after the meal containing D-chiroinositol compared to the control meal (7.1 +/- 1.2 vs. 7.8 +/- 1.2 mM) (p < 0.05). Plasma insulin concentrations tended to be lower after the meal containing D-chiroinositol compared to the control meal (3930 +/- 1068 vs. 4518 +/- 1200 pM) (p < 0.15, ns). We conclude that in hyperinsulinemic monkeys, D-chiroinositol added to a meal lowers postprandial plasma glucose without an increase in plasma insulin, and therefore may be a useful agent for reducing meal-induced hyperglycemia without inducing hyperinsulinemia.

Animals↗
PubMed1995

Prevention of obesity in middle-aged monkeys: food intake during body weight clamp.

Prevention of obesity and increase in longevity in obesity-prone rodents can be achieved by long-term moderate dietary restriction. In order to examine the likelihood that caloric restriction could have similar salutary effects in humans, rhesus monkeys, after reaching mature adult stature, were placed on a protocol to clamp or stabilize body weight by weekly caloric adjustment. Furtherweight gain was prevented by this caloric titration procedure, and thus middle-age onset obesity, which is very common in this species, was prevented. The present study analyzed daily food intake for six weight-clamped monkeys and six ad libitum fed age-matched animals over a 3-year period, ages 18.5 to 21.5 years. After approximately 9 years of caloric restriction the daily calorie load to maintain stable adult body weight proved to be 40% less than the amount ingested by ad libitum fed animals. Calories per kg body weight did not differ significantly between the groups although the ad libitum fed animals were significantly fatter than the weight-clamped group. Prevention of obesity using this weight clamp protocol has also maintained lower insulin levels and higher glucose tolerance in the restricted animals.

Age Factors↗
PubMed1995

Effects of Acipimox on the metabolism of free fatty acids and very low lipoprotein triglyceride.

The mechanism of triglyceride lowering by Acipimox, a nicotine acid analogue, was examined in a group of five moderately hypertriglyceridemic male rhesus monkeys. Two experiments were designed to examine the effect of the drug on lipid and glucose metabolism in nondiabetic, insulin-resistant animals. A single dose of Acipimox (8 mg/kg) given with a meal lowered the plasma free fatty acids (FFA) significantly at 4 h (0.102 +/- 0.008 vs 0.154 +/- 0.020 g/l; mean +/- SEM; P < 0.03); however, FFA concentrations returned to control levels at 6 h. Chronic administration of Acipimox (16 mg/kg q. i. d.) for 2 months produced a 31% reduction in triglyceride concentration (P < 0.05) and a significant decrease in low density lipoprotein (LDL)-cholesterol (P < 0.04), without changes in insulin action as measured by the hyperinsulinemic euglycemic clamp. Fasting FFA concentrations were not significantly altered by chronic treatment (0.163 +/- 0.013 versus 0.140 +/- 0.034 g/l). Fatty acid metabolic studies indicated increases in FFA transport (203.7 +/- 59.1 versus 136.1 +/- 26.6 microEq/min; P < 0.05), while FFA fractional clearance rate (FCR) was unchanged. Very low density lipoprotein triglyceride (VLDL-Tg) metabolic experiments, using [3H]glycerol, showed increases in production and FCR with the drug. Increased VLDL-Tg clearance, in spite of increased production of VLDL, appears to be the mechanism by which triglycerides are lowered upon chronic Acipimox administration.

Animals↗