Glucosamine and chondroitin sulfate

Glucosamine and chondroitin sulfate, components of normal cartilage that are marketed as dietary supplements in the United States, have been evaluated for their potential role in the treatment of osteoarthritis. Due to claims of efficacy, increased prevalence of osteoarthritis, and a lack of other effective therapies, there has been substantial interest in using these dietary supplements as therapeutic agents for osteoarthritis. Though pharmacokinetic and bioavailability data are limited, use of these supplements has been evaluated for management of osteoarthritis symptoms and modification of disease progression. Relevant clinical trial efficacy and safety data are reviewed and summarized.     

硫酸软骨素和硫酸氨基葡萄糖对成人大骨节病的疗效分析

目的 观察硫酸软骨素和硫酸氨基葡萄糖对大骨节病的疗效.方法 2007年7月,在黑龙江省尚志市光辉村按<大骨节病诊断标准>检出患者80例.按病情等级、年龄、性别将80例患者分成治疗组、对照组.每组40人.治疗组给予硫酸软骨素和硫酸氨基葡萄糖治疗,对照组给予安慰剂(等量淀粉).在治疗前及治疗后(第8个月)对患者进行直立体位的膝关节X线拍片,利用刻度放大镜测量X线膝关节腔宽度.结果 对照组治疗前、后的X线膝关节腔宽度分别为(4.30±2.14)、(4.10±2.07)mm,治疗组分别为(4.17±2.15)、(4.16±2.11)mm.药物对X线关节腔宽度没有影响(F=0.50,P>0.05),时间、药物与时间的交互作用对X线关节腔宽度有影响(F值分别为67.66、46.74,P均<0.05).治疗组X线关节腔宽度治疗前低于对照组(P<0.05),治疗后高于对照组(P<0.05);对照组治疗前X线关节腔宽度高于治疗后(P<0.05).结论 硫酸软骨素和硫酸氨基葡萄糖减缓了成人大骨节病患者膝关节间隙继续变窄的进程,对关节软骨起到了保护作用,为成人大骨节病治疗在药物选择和疗效判定上提供了依据.     

Combined glucosamine and chondroitin sulfate provides functional and structural benefit in the anterior cruciate ligament transection model

Evidence that combined glucosamine sulfate and chondroitin sulfate (Gluchon) or isolated glucosamine (Glu) modifies joint damage in osteoarthritis (OA) is still lacking. We studied joint pain and cartilage damage using the anterior cruciate ligament transection (ACLT) model. Wistar rats were subjected to ACLT of the right knee (OA) or sham operation. Groups received either Glu (500 mg/kg), Gluchon (500 mg/kg glucosamine +400 mg/kg chondroitin) or vehicle (non-treated—NT) per os starting 7 days prior to ACLT until sacrifice at 70 days. Joint pain was evaluated daily using the rat-knee joint articular incapacitation test. Structural joint damage was assessed using histology and biochemistry as the chondroitin sulfate (CS) content of cartilage by densitometry (microgram per milligram dried cartilage), comparing to standard CS. The molar weight (Mw) of the CS samples, used as a qualitative biochemical parameter, was obtained by comparing their relative mobility on a polyacrylamide gel electrophoresis to standard CS. Gluchon, but not Glu, significantly reduced joint pain (P < 0.05) compared to NT. There was an increase in CS content in the OA group (77.7 ± 8.3 μg/mg) compared to sham (53.5 ± 11.2 μg/mg) (P < 0.05). The CS from OA samples had higher Mw compared to sham (P < 0.05). Gluchon administration significantly reversed both the increases in CS content (54.4 ± 12.1 μg/mg) and Mw as compared to NT. Isolated Glu decreased CS content though not reaching statistical significance. Cartilage histology alterations were also significantly prevented by Gluchon administration. Gluchon provides clinical (analgesia) and structural benefits in the ACLT model. This is the first demonstration that biochemical alterations occurring in parallel to histological damage in OA are prevented by Gluchon administration.     

硫酸软骨素对大鼠酒精性脂肪肝模型的影响

目的 观察硫酸软骨素对酒精性脂肪肝的治疗作用。方法 用连续灌服酒精的方法建立大鼠酒精性脂肪肝模型。在造模成功后给予硫酸软骨素治疗4周，观察一般情况及测定血清肝功能指标和血脂参数，并对大鼠肝脏行病理学检查。结果 连续灌服酒精8周后大鼠形成酒精性脂肪肝，给药4周后，硫酸软骨素（25mg/kg）组成显著降低血中丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）活性与血中和肝脏中丙二醛（MDA），甘油三酯（TG），总胆固醇（TC）含量，改善肝脏炎症活动度与脂肪性变。结论 硫酸软骨素能改善酒精性脂肪肝大鼠体内脂质代谢，对酒精性脂肪肝具有一定的治疗作用。     

Hepatotoxicity associated with glucosamine and chondroitin sulfate in patients with chronic liver disease

Glucosamine and chondroitin sulfate are molecules involved in the formation of articular cartilage and are frequently used for symptom relief in patients with arthrosis.These molecules are well tolerated with scarce secondary effects.Very few cases of possible hepatotoxicity due to these substances have been described.The aim of this paper is to report the frequency of presumed glucosamine hepatotoxicity in patients with liver disease.A questionnaire was given to 151 consecutive patients with chronic liver disease of different etiology(mean age 59 years,56.9%women)attended in an outpatient clinic with the aim of evaluating the frequency of consumption of these drugs and determine whether their use coincided with a worsening in liver function test results.Twenty-three patients(15.2%)recognized having taken products containing glucosamine or chondroitin sulfate previously or at the time of the questionnaire.Review of the clinical records and liver function tests identified 2 patients presenting an elevation in aminotransferase values temporarily associated with glucosamine treatment;one of the cases simultaneously presented a skin rash attributed to the drug.Review of these two patients and the cases described in the literature suggest toxicity of glucosamine and chondroitin sulfate.The clinical spectrum is variable,and the mechanism of toxicity is not clear but may involve reactions of hypersensitivity.The consumption of products containing glucosamine and/or chondroitin sulfate is frequent among patients with chronic liver diseases and should be taken into account on the appearance of alterations in liver function tests not explained by the underlying disease.     

Importance of synovitis in osteoarthritis: Evidence for the use of glycosaminoglycans against synovial inflammation

Objectives

After detailing the different aspects of synovial inflammation (i.e., cellular, biochemical, and vascular) and based on the current knowledge, the aim of this review was to collect the available in vitro and in vivo data regarding the potency of some glycosaminoglycan (GAG) compounds to target synovial inflammation, an important aspect of osteoarthritis.

Methods

The first part of the review corresponds to a qualitative review of the inflammatory status of OA synovial membrane. The second part corresponds to a systematic review of the literature regarding the potential effects of some GAGs on the previously described phenomenon.

Results

The synovial aspect of the inflammatory status of OA has been detailed. Chondroitin sulfate has demonstrated to control the three aspects of synovial membrane inflammation: cell infiltration and activity, biochemical mediators release, and angiogenesis. Glucosamine is also active on both cellular and molecular aspects of the inflammatory reaction. Hyaluronic acid seems to be anti-inflammatory in its native form, while products of degradation are reported to be pro-angiogenic.

Conclusion

Much evidence suggests that some of the studied GAG compounds could target different aspects of synovitis. Some of them could be considered in combination therapy since they exhibit complementary properties. Most of the studies have concentrated on articular cartilage and chondrocytes. In order to achieve a structure modification, one may now consider all joint tissues and investigate the drug potency on all of them. Potent treatment should trigger the most important features of OA: cartilage degradation, subchondral bone sclerosis, and all aspects of synovial inflammation.     

颞下颌关节紊乱病患者关节滑液硫酸软骨素含量变化及意义

目的观察颞下颌关节紊乱病(TMD)患者关节滑液中硫酸软骨素(CS)的含量变化,探讨其在TMD诊断中的价值.方法用高效液相色谱法检测10例正常人颞下颌关节(对照组)、32例颞下颌关节结构紊乱病(ID组)、28例颞下颌关节骨关节病(OA组)患者关节滑液中CS不饱和二糖ΔDi-6S与ΔDi-4S.结果三组关节滑液中均能检测出ΔDi-6S,ID组及OA组均检测到ΔDi-4S,对照组仅有3例检测到痕量ΔDi-4S.ΔDi-6S与ΔDi-4S含量在ID组及OA组均高于对照组(P均＜0.001),OA组亦高于ID组(P＜0.01).结论 TMD患者关节滑液中CS含量增加,且随病变的加重CS含量增加,其可以作为一种生化标志用于TMD的早期诊断.     

Dermatan sulfate in the synovial fluid of patients with knee osteoarthritis

Biochemical factors play an important role in osteoarthritis (OA) pathogenesis. The purpose of this study is to clarify whether the dermatan sulfate (DS) levels in the synovial fluid of patients with knee OA are related to residual cartilage. Synovial fluid was obtained from 51 OA patients. Knee radiographs were evaluated with the Kellgren–Lawrence (K/L) grading scale. The levels of the following disaccharides were measured by high-performance liquid chromatography (HPLC): DS (DSΔDi4S), chondroitin 6-sulfate (CSΔDi6S), and chondroitin 4-sulfate (CSΔDi4S). The concentration of cartilage oligomeric matrix protein (COMP) was measured by a sandwich ELISA. The levels of DSΔDi4S in Grades 0 and I OA were significantly higher than levels in Grade II (P = 0.0458), Grade III (P < 0.0001) and Grade IV (P < 0.0001), and we found strong relationships between the levels of DSΔDi4S and those of CSΔDi6S (P < 0.0001, r = 0.705), CSΔDi4S (P < 0.0001, r = 0.750), and COMP (P < 0.0001, r = 0.699). We conclude that the presence of DSΔDi4S reflects proteoglycan metabolism in the residual articular cartilage of OA patients. This suggests that metabolism of the small leucine-rich repeat proteoglycans decorin and biglycan, which contain chains of DSΔDi4S, is similar to that of aggrecan.     

高效液相色谱柱后衍生荧光法测定尿液中硫酸软骨素分解产生的不饱和双糖

目的 探讨高效液相色谱柱后衍生荧光法测定尿液中硫酸软骨素(CS)分解产生的不饱和双糖的效果.方法 分别用离心过滤法和常规沉淀法进行尿液的预处理,处理后的样品加CS裂解酶消化,用高效液相色谱柱后衍生荧光法测定分解产生的不饱和双糖(ADi-0S、△Di-4S、ADi-6S)的量,比较两种预处理方法中CS标准品回收率的差别.结果 高效液相色谱柱后衍生荧光检测系统运转效果良好,该法对于双糖的最低检出量为10 ng.尿样经离心过滤法处理后,CS标准品分解产生的△Di-0S、△Di-4S、△Di-6S的回收率分别为86.93%、87.28%、85.03%;而在常规沉淀法中,3种双糖的回收率仅为75.09%、72.96%、77.70%.结论 高效液相色谱柱后衍生荧光法较为灵敏,可用于测定CS分解产生的不饱和双糖.在尿液样品的预处理方法中,离心过滤法优于常规沉淀法,可应用于尿液中CS的微量测定.     

Age-related changes and sex differences in chondroitin sulfate isomers and hyaluronic acid in normal synovial fluid

The effects of factors such as age and sex on the metabolism of chondroitin sulfate (CS) and hyaluronic acid (HA) in knee joint tissues are believed to be profoundly important in the onset of joint diseases including osteoarthritis. To test whether age and sex influence CS isomers and HA in normal synovial fluid, we determined concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and HA in healthy subjects of different ages. Synovial fluids were obtained from 187 healthy volunteers, 14–89 years of age. Chondroitin 6-sulfate, C4S, HA concentrations, and C6S : C4S ratio showed a significant negative correlation with age. There were no sex-related differences in HA concentration, but the concentrations of C6S and C4S and the C6S : C4S ratio were significantly lower in women than in men in most age groups.     

Age-related changes and sex differences in chondroitin sulfate isomers and hyaluronic acid in normal synovial fluid

Abstract

The effects of factors such as age and sex on the metabolism of chondroitin sulfate (CS) and hyaluronic acid (HA) in knee joint tissues are believed to be profoundly important in the onset of joint diseases including osteoarthritis. To test whether age and sex influence CS isomers and HA in normal synovial fluid, we determined concentrations of chondroitin 6-sulfate (C6S), chondroitin 4-sulfate (C4S), and HA in healthy subjects of different ages. Synovial fluids were obtained from 187 healthy volunteers, 14–89 years of age. Chondroitin 6-sulfate, C4S, HA concentrations, and C6S?:?C4S ratio showed a significant negative correlation with age. There were no sex-related differences in HA concentration, but the concentrations of C6S and C4S and the C6S?:?C4S ratio were significantly lower in women than in men in most age groups.     

云克与硫酸软骨素联合用药治疗成人大骨节病的临床效果观察

目的 通过锝[99TC]亚甲基二磷酸盐(云克)与硫酸软骨素联合用药观察药物疗效,为临床治疗成人大骨节病提供科学数据.方法 按照《大骨节病诊断标准》(GB 16003-1995),在呼伦贝尔市大骨节病病区选择79例大骨节病患者,分为治疗组与对照组.治疗组44人,给予静脉注射云克和口服硫酸软骨素;对照组35人,仅静脉注射云克.3个月后观察效果[以治疗前后疼痛、功能改善情况、骨关节炎指数(WOMAC)变化情况进行判定].结果 治疗组和对照组经过3个月治疗后,疼痛症状及关节功能恢复显效率分别为81.82％(36/44)和60.00％(21/35);有效分别为15.91％(7/44)和34.29％(12/35);无效分别为2.72％ (1/44)和5.71％(2/35);总有效率分别为97.73％(43/44)和94.29％(33/35).治疗组和对照组患者治疗前后握力、15 m步行时间、血钙、WOMAC指数比较,差异均有统计学意义(治疗组t=3.37、7.99、8.73、16.19,P均＜0.05;对照组t=6.21、9.46、5.49、8.73,P均＜0.05).两组之间疗效比较差异无统计学意义(x2=1.06,P＞ 0.05).结论 云克与硫酸软骨素联合或单独用药,都是目前治疗大骨节病理想、疗效可靠的药物治疗方法,值得临床推广应用.     

Unusual case of drug-induced cholestasis due to glucosamine and chondroitin sulfate

Glucosamine(GS) and chondroitin sulfate(CS) are common over-the-counter(OTC) supplements used in the treatment of osteoarthritis. These medications are seemingly safe, but there are increasing reports of hepatotoxicity with these supplements. We reported a unique case of drug-induced cholestasis caused by GS and CS in a combination tablet. The etiology of the jaundice was overlooked despite extensive investigations over a three-month period. Unlike drug-induced hepatocellular injury, drug-induced cholestatic jaundice with GS and CS has only been reported twice before. This case emphasizes the importance of a complete medication history, especially OTC supplements, in the assessment of cholestasis.     

硫酸氨基葡萄糖对白细胞介素1β诱导人骨关节炎软骨细胞合成前列腺素E2的影响

目的探讨硫酸氨基葡萄糖(glucosamine sulfate,GS)对白细胞介素1β(IL-1β)诱导体外培养的人骨关节炎软骨细胞(human osteoarthritic chondrocyte,HOC)合成前列腺素E_2 (prostaglandin E_2,PGE_2)的影响及其作用机制。方法取10例骨关节炎患者行全膝关节置换术的股骨髁和胫骨平台软骨标本,酶消化法获取软骨细胞进行体外培养。在原代或第二代的HOC培养液中加入IL-1β(5×10~(-3)μg/L)和不同浓度的GS(0.2、2和20 mmol/L)作用24 h(对照组不加IL-1β和GS),首先应用ELISA法检测GS对IL-1β诱导HOC合成PGE_2的影响,然后采用RT-PCR法和Western蛋白印迹法分别检测其对IL-1β诱导HOC表达COX-2 mRNA和蛋白的影响。结果对照组HOC培养液中PGE_2浓度为(109.46±17.48)pg/ml,IL-1β刺激后软骨细胞合成PGE_2为(3607.22±239.34)pg/ml,其差异有统计学意义(P<0.01)。0.2、2和20 mmol/L GS以浓度依赖的方式抑制IL-1β诱导HOC合成PGE_2(P<0.05),其浓度分别为(2594.23±185.18)、(1057.53±126.81)和(565.43±52.79)pg/ml;单独使用20 mmol/L GS时软骨细胞合成PGE_2为(169.94±30.03)pg/ml,与对照差异无统计学意义(P>0.05)。IL-1β刺激后,HOC表达COX-2 mRNA和蛋白上调(P<0.01),GS能以浓度依赖的方式抑制IL-1β诱导HOC表达COX-2 mRNA和蛋白上调(P<0.01)。结论GS抑制HOC在IL-1β诱导下分泌炎性介质PGE_2,其机制是下调调控它们表达的COX-2 mRNA和蛋白的表达;这可能是GS既能缓解症状和又能保护软骨的机制之一。     

Changes of serum apolipoprotein levels after oral administration of fat in human subjects

Changes of serum apolipoprotein levels were studied every hour for 6 h after the administration of 55 g butter to 8 healthy male subjects. The mean serum apo A-IV level was significantly increased at 4 h (P less than 0.05) after fat ingestion compared to the mean initial level, although no significant changes of levels in other apolipoproteins (apo A-I, A-II, B, C-II, C-III, and E) were observed. The mean apo A-IV level in the triglyceride-rich lipoprotein (TRL) fraction (d less than 1.006) increased progressively over 6 h. In all 8 subjects, the time of peak concentration of apo A-IV in TRL fraction was delayed by 1-2 h compared to that in whole serum. On the other hand, the mean apo B-48 level in the fraction reached a peak at 4 h. These results raise the possibilities that some apo A-IV, newly synthesized or already existing in intestinal cells, may be directly secreted into the venous circulation and that apo A-IV and apo B-48 may distribute differently in different sizes of chylomicron. Alternatively, the amount of each apolipoprotein synthesized may depend upon the content of ingested fat. It is suggested that apo A-IV production by intestinal cells does not appear to be regulated by the rate of fat transport, and that apo A-IV does not play an important role in chylomicron formation compared to apo B-48.     

Effects of appendectomy and oral tolerance on dextran sulfate sodium colitis

To evaluate the concomitant effects of appendectomy and oral tolerance on colitis.METHODS:Delayed-type hypersensitivity (DTH) was investigated at a 7-d interval after ovalbumin (OVA) administration and immunization under normal and colitis conditions in appendectomized or sham-operated mice.Pathological scores for the colon were graded after ingestion of colon-extracted protein (CEP) and induction of dextran sulfate sodium (DSS) colitis in appendectomized or sham-operated mice.Thereafter,Th1 and Th2 in Peye...     

The epidermal growth factor-like domains of the human EMR2 receptor mediate cell attachment through chondroitin sulfate glycosaminoglycans

Using multivalent protein probes, an evolutionarily conserved endogenous ligand for EMR2, a human myeloid cell-restricted EGF-TM7 receptor, was identified on the surface of a number of adherent cell lines. In addition, in situ staining of the ligand has revealed specific in vivo patterns consistent with a connective tissue distribution. The interaction is conserved across species and mediated exclusively by the largest EMR2 isoform containing 5 epidermal growth factor (EGF)-like modules. Antibody-blocking studies subsequently revealed that the fourth EGF-like module constitutes the major ligand-binding site. The largest isoform of CD97, a related EGF-TM7 molecule containing an identical EGF-like module, also binds to the putative EMR2 ligand. Through the use of mutant Chinese hamster ovary (CHO) cell lines defective in glycosaminoglycans (GAGs) biosynthesis as well as the enzymatic removal of specific cell surface GAGs, the molecular identity of the EMR2 ligand was identified as chondroitin sulfate (CS). Thus, exogenous CS GAGs blocked the EMR2-ligand interaction in a dose-dependent manner. EMR2-CS interaction is Ca2+- and sulphation-dependent and results in cell attachment. This is the first report of a GAG ligand for the TM7 receptors extending the already vast repertoire of stimuli of the GPCR superfamily.     

The behaviour of blood sugar and serum insulin (IRI) after oral administration of glucose in different stages of myocardial infarction

Summary The blood sugar response and serum insulin level after oral administration of glucose were studied in 10 patients in the acute stage of myocardial infarction and during convalescence. In 4 of the patients with an abnormal glucose tolerance curve during convalescence the test was repeated one year later. The blood sugar response was abnormal in 7 patients and 3 of them showed hypoinsulinaemia in the acute stage of the infarction. Both in the early and late stages of myocardial infarction the mean serum insulin values were significantly below those in controls. The factors which may be responsible for disturbed carbohydrate metabolism in patients with myocardial infarction ore discussed.

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Zusammenfassung Bei 10 Patienten mit Myokardinfarkt wurden sowohl in der akuten Phase als auch während der Rekonvaleszenz die Reaktion des Blutzuckers und des Insulinspiegels (Serum-IRI) auf die orale Verabreichung von Glukose untersucht. Bei 4 Probanden, welche während der Rekonvaleszenz eine veränderte Glukosetoleranz zeigten, wurde die Probe ein Jahr später wiederholt. Bei 7 Patienten fand sich eine abnorme Reaktion des Blutzuckers, bei 3 von diesen war in der akuten Phase des Infarktes der Insulinserumspiegel niedriger. Die Mittelwerte des Seruminsulins waren signifikant vermindert im Vergleich zu den Kontrollpersonen und zwar sowohl im akuten Stadium als auch während der Rekonvaleszenz. Es werden die Faktoren besprochen, die möglicherweise für diese Veränderung des Kohlehydratstoffwechsels bei Herzinfarkt verantwortlich sind.

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Resumen En 10 pacientes con infarto del miocardio se ha estudiado, tanto en la fase aguda, como durante la convalecencia, la respuesta glicémica e insulinémica (IRI suerosa) al suministro oral de glucosa. En 4 individuos que presentaban una tolerancia a la glucosa alterada durante la convalecencia, la prueba se ha repetido un año más tarde. La respuesta glicémica resultó anormal en 7 pacientes; 3 de ellos manifestaban hipoinsulinemia en la fase aguda del infarto. Los valores medios de la insulina suerosa eran significativamente inferiores a los de los controles tanto en la fase aguda del infarto como en la tardía. Se discuten los posibles factores responsables de la alteración del metabolismo glucídico en los pacientes con infarto del miocardio.

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Résumé En 10 patients avec infarctus du myocarde, on a étudié, tant dans la phase aiguë que pendant la convalescence, la réponse glycémique et insulinémique (IRI sérique) à l'administration orale de glucose. En 4 sujets qui présentaient une tolérance altérée au glucose pendant la convalescence, le test a été répété un an plus tard. La réponse glycémique était anormale en 7 patients; 3 de ceux-ci avaient une hypoinsulinémie dans la phase aiguë de l'infarctus. Les valeurs moyennes de l'insuline sérique étaient sensiblement inférieures à celles des contrôles, tant dans la phase aiguë que dans la phase tardive de l'infarctus. On discute les facteurs responsables de l'altération de l'échange glucidique dans les patients avec infarctus du myocarde.

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Riassunto In 10 pazienti con infarto del miocardio sono state studiate, sia nella fase acuta che durante la convalescenza, le risposte glicemica ed insulinemica (IRI sierica) alla somministrazione orale di glucosio. In 4 soggetti che presentavano un'alterata tolleranza al glucosio durante la convalescenza, la prova è stata ripetuta un anno più tardi. La risposta glicemica è risultata anormale in 7 pazienti; 3 di questi mostravano ipoinsulinemia nella fase acuta dell'infarto. I valori medî dell'insulina sierica erano significativamente inferiori a quelli dei controlli, sia nella fase acuta che in quella tardiva dell'infarto. Vengono discussi i possibili fattori responsabili dell'alterazione del ricambio glicidico nei pazienti con infarto del miocardio.

     

Insulin and metabolism of glycosaminoglycans in rabbits

Summary The effect of insulin on the concentration of different glycosaminoglycan (GG) fractions was different in different segments of aorta. Chondroitin sulphate A and heparin were increased in the aortic arch, thoracic and abdominal aorta, while chondroitin sulphate B and C were increased only in the aortic arch and abdominal aorta. Heparin sulphare and hyaluronic acid were increased only in the abdominal aorta. In the liver, significant increases occurred in all GG fractions. All enzymes studied which are involved in the biosynthesis of GG precursors,i.e. glucosaminphosphate isomerase, UDP glucose dehydrogenase and glucose-1-phosphate uridylyltransferase, were increased in the animals of the insulin group, while all enzymes involved in the degradation of GG,i.e. hyalurono glucosidase, β-glucuronidase, β-glucosaminidase, arylsulphatase and cathepsin D, were decreased. Concentration of hepatic PAPS, activity of the sulphate-activating system and sulphotransferase increased on administration of insulin.     

Changes in serum apolipoprotein B concentration after oral glucose or intramuscular insulin

Summary An oral glucose load or a single i.m. insulin injection given to normal human subjects was followed within 1 h by a fall in total serum apolipoprotein B concentration. Although both procedures caused a concomitant drop in serum albumin concentration, the apolipoprotein-B/albumin ratio fell significantly, indicating that the drop in serum apolipoprotein B concentration cannot be explained by hemodilution.