Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion.

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.     

No acute effects of smoking and nicotine nasal spray on lipolysis measured by subcutaneous microdialysis

Smoking is associated with insulin resistance, dyslipidaemia and markers of the insulin resistance syndrome. This study investigated adipose tissue lipolysis in situ by subcutaneous microdialysis twice in 10 healthy, male smokers after smoking four cigarettes over 2 h and after the administration of an equal amount of nicotine given as nasal spray (NNS). Glucose and insulin levels, in situ lipolysis and adipose tissue blood flow were studied in the post-absorptive state and after a 75-g oral glucose tolerance test (OGTT). Post-absorptively, acute smoking and NNS increased neither subcutaneous adipose tissue glycerol production nor plasma free fatty acid (FFA) or glycerol levels. After the OGTT, plasma insulin and lactate levels were significantly higher after smoking, whereas FFA levels were higher after NNS. Normal smoking or the administration of a normal dose of NNS caused only minor metabolic changes. Thus, it does not seem likely that increased lipolysis is an important contributor to the dyslipidaemia seen in smokers.     

Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats

We investigated the chronic in vivo effect of resistin on insulin sensitivity and glucose metabolism by overexpressing resistin protein in male Wistar rats using intravenous administration of an adenovirus encoding mouse resistin. After 7 days of elevated resistin levels at a supraphysiological concentration, the animals displayed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. The glucose clamp studies were performed at submaximal (4 mU/kg/min) and maximal (25 mU/kg/min) insulin infusion rates and demonstrated the presence of insulin resistance induced by elevated resistin levels. Indeed, the insulin-stimulated glucose infusion rate was decreased by 12-31%; suppression of hepatic glucose output was attenuated by 28-55%; and insulin suppression of circulating FFA levels was inhibited by 7%. Insulin receptor substrate-1 and -2 phosphorylation and Akt activation were impaired in muscle and adipose tissue. Interestingly, activation of AMP-activated protein kinase in skeletal muscle, liver, and adipose tissue was also significantly downregulated. Together, these results indicate that chronic "hyper-resistinemia" leads to whole-body insulin resistance involving impaired insulin signaling in skeletal muscle, liver, and adipose tissue, resulting in glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. Thus elevated resistin levels in normal rats fed a regular chow diet produce many of the features of human syndrome X.     

高血压病患者血清抵抗素浓度与游离脂肪酸水平的相关性研究

目的　探讨人血清抵抗素浓度与游离脂肪酸 (FFA)水平的关系。方法　检测 71例高血压患者空腹血清抵抗素水平 ;口服葡萄糖耐量试验和胰岛素释放试验 ,测定血浆葡萄糖浓度、血清胰岛素浓度、FFA水平。计算体内脂肪百分比 (BF % )。结果　相关分析显示 ,空腹血清抵抗素浓度与口服葡萄糖后 30分钟时相点FFA(0 .5hFFA)水平呈显著正相关 ,与空腹血清FFA、口服葡萄糖后 6 0分钟时相点FFA和 12 0分钟时相点FFA水平无关 ;校正年龄、性别和BF %后的偏相关分析显示 ,空腹血清抵抗素浓度与 0 .5hFFA仍呈显著正相关。结论　高血压病患者血清抵抗素浓度与 0 .5hFFA直接相关 ,提示抵抗素对人FFA代谢可能有重要的影响。     

Investigations of the effect of midodrine on carbohydrate and fat metabolism with particular reference to the diabetic metabolic state (author's transl)]

Midodrine, which is used in the treatment of hypotensive circulatory distrubances was investigated with respect to possible effects on carbohydrate and fat metabolism in 5 healthy subjects and 7 patients with disturbed glocuse tolerance. An i.v. glucose tolerance test was carried out on both groups and was repeated a few days subsequently with simultaneous administration of midodrine (5mg i.v.). Midodrine had no significant effect on glucose tolerance in either group, nor was there any significant effect of midodrine on FFA, serum insulin, triglyceride or cholesterol levels. 15 diabetic patients controlled by different therapeutic regimens (5 by diet only, 5 by oral preparations and 5 by insulin treatment) were given 3x5mg midodrine orally over a 5-day period and the effects on diabetic control and metabolic parameters compared with a 5-day pretreatment period without midodrine. Midodrine did not cause any change in the quality of diabetic control nor any significant alteration in serum lipid or uric acid levels.     

Studies of substrate regulation in fasting: II. Effect of infusion of glucose into the carotid artery upon fasting lipolysis in the baboon

The effect of glucose infusion on rates of lipolysis were studied in a group of chair-trained papio baboons that had been prepared for chronic intravenous and intracarotid infusion. All studies were carried out after a 24 hr period of fasting and when the animals were fully awake. After a control interval of 1 hr, a glucose infusion was begun either intravenously or intra-arterially. The infusion was continued at a constant rate for 2 hr and then changed directly to the alternate route and continued an additional 2 hr. Blood samples were collected at 30-min intervals for glucose, free fatty acid (FFA), glycerol, insulin, and in some studies, growth hormone (GH) determination. When glucose doses less than 0.5 mg/kg per min were used, no change in the products of lipolysis was noted during either venous or carotid administration, and glucose and insulin levels remained stable or fell gradually. With doses of glucose between 0.5 and 0.6 mg/kg per min, a greater fall in both FFA and glycerol was noted during carotid administration. No definite changes in plasma glucose or insulin levels were noted during either infusion period. These changes in lipolysis were noted regardless of the sequence of infusion, and a similar differential suppression of FFA was noted during a 24 hr period of carotid glucose administration. When doses of glucose larger than 0.6 mg/kg per min were used, inhibition of lipolysis was noted during both phases of infusion. No definite change in GH levels was noted during the periods of fasting, and the levels of the hormone did not appear to be related to changes in glucose, insulin, or FFA levels.These data provide additional evidence for the presence in the central nervous system of a glucose-sensitive center which alters lipolytic rates independently of insulin and GH, probably by altering sympathetic tone to adipose tissue.     

Interaction between glucose and free fatty acid metabolism in human skeletal muscle.

The mechanism by which FFA metabolism inhibits intracellular insulin-mediated muscle glucose metabolism in normal humans is unknown. We used the leg balance technique with muscle biopsies to determine how experimental maintenance of FFA during hyperinsulinemia alters muscle glucose uptake, oxidation, glycolysis, storage, pyruvate dehydrogenase (PDH), or glycogen synthase (GS). 10 healthy volunteers had two euglycemic insulin clamp experiments. On one occasion, FFA were maintained by lipid emulsion infusion; on the other, FFA were allowed to fall. Leg FFA uptake was monitored with [9,10-3H]-palmitate. Maintenance of FFA during hyperinsulinemia decreased muscle glucose uptake (1.57 +/- 0.31 vs 2.44 +/- 0.39 mumol/min per 100 ml tissue, P < 0.01), leg respiratory quotient (0.86 +/- 0.02 vs 0.93 +/- 0.02, P < 0.05), contribution of glucose to leg oxygen consumption (53 +/- 6 vs 76 +/- 8%, P < 0.05), and PDH activity (0.328 +/- 0.053 vs 0.662 +/- 0.176 nmol/min per mg, P < 0.05). Leg lactate balance was increased. The greatest effect of FFA replacement was reduced muscle glucose storage (0.36 +/- 0.20 vs 1.24 +/- 0.25 mumol/min per 100 ml, P < 0.01), accompanied by decreased GS fractional velocity (0.129 +/- 0.26 vs 0.169 +/- 0.033, P < 0.01). These results confirm in human skeletal muscle the existence of competition between glucose and FFA as oxidative fuels, mediated by suppression of PDH. Maintenance of FFA levels during hyperinsulinemia most strikingly inhibited leg muscle glucose storage, accompanied by decreased GS activity.     

睾酮对3T3-L1脂肪细胞糖脂代谢的影响

目的观察睾酮对3T3-L1脂肪细胞糖脂代谢的影响及胰岛素增敏剂的干预作用。方法体外培养3T3-L1前脂肪细胞,并诱导其分化成熟,研究睾酮对脂肪细胞葡萄糖消耗量及甘油三酯(TG)、游离脂肪酸(FFA)和甘油(Gly)等指标的影响及胰岛素增敏剂的干预作用。结果 5×10-7mol/L的睾酮刺激组葡萄糖消耗量明显降低,二甲双胍及吡格列酮处理组较睾酮组葡萄糖消耗量有所增加,睾酮刺激组较对照组TG增高,而Gly和FFA降低,二甲双胍和吡格列酮处理后,可使TG降低及Gly和FFA升高。结论环境中存在一定浓度的睾酮对脂肪细胞的糖脂代谢都有着不利的影响,而胰岛素增敏剂二甲双胍、吡格列酮可以改善这种不利影响。     

Women with polycystic ovary syndrome are sensitive to the TNF-alpha-lowering effect of glucose-induced hyperinsulinaemia

BACKGROUND: Restoration of near-euglycaemia by intensive insulin therapy results in decreased serum levels of inflammatory mediators. The authors investigated whether the anti-inflammatory effect of insulin was independent of its glucose-lowering action and if this effect was intact in insulin-resistant women with the polycystic ovary syndrome (PCOS) characterized by low-grade chronic inflammation. MATERIALS AND METHODS: Blood was drawn on the third and sixth days after progestin-induced withdrawal bleeding in 20 young non-diabetic women with PCOS and once between the third and sixth days of the menstrual cycle in 21 age-matched lean healthy control women during a 75-g oral glucose tolerance test (oGTT). Serum insulin, glucose and tumour necrosis factor alpha (TNF-alpha) concentrations were measured after 0, 30, 60, 90 and 120 min. RESULTS: The increase in insulin and glucose concentrations during the oGTT was significantly more pronounced in patients with PCOS (one patient with impaired fasting glucose, one patient with impaired glucose tolerance, three patients with both) compared with healthy controls. The TNF-alpha serum concentrations decreased in patients with PCOS (mean of both days, P = 0.004). In patients and in controls, there was an inverse correlation between the serum concentrations of insulin and of TNF-alpha during oGTT (for patients, a mean of both days, P = 0.009; for controls, P = 0.047), but not between the serum concentrations of glucose and TNF-alpha. CONCLUSIONS: The decrease in TNF-alpha concentrations during oGTT and the inverse correlation between endogenous hyperinsulinaemia and serum TNF-alpha concentrations suggested an anti-inflammatory effect of moderately-high insulin concentrations. This occurred despite the presence of moderate hyperglycaemia. These findings also demonstrated a preserved responsiveness of inflammatory mediators to insulin in PCOS.     

Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion

The disposition of methylprednisolone was examined in six normal subjects after the injection of 20 mg iv methylprednisolone sodium succinate. Disposition studies were performed both without and with ketoconazole, 200 mg/day, for 6 days. Ketoconazole increased the methylprednisolone AUC and mean residence time (by 135% and 66%, respectively) and decreased clearance (60%), the terminal phase slope, and the volume of distribution. These findings are typical of macrolide antibiotic alteration of methylprednisolone disposition and consistent with reports of inhibition of drug metabolism by ketoconazole. Methylprednisolone reduced the 24-hour cortisol AUC by 44%, but morning cortisol concentrations returned to normal. Ketoconazole with methylprednisolone further reduced the 24-hour cortisol AUC and suppressed morning cortisol concentrations. Thus ketoconazole inhibits methylprednisolone disposition and extends the adrenal suppression effects of this corticosteroid.     

Demonstration of a critical role for free fatty acids in mediating counterregulatory stimulation of gluconeogenesis and suppression of glucose utilization in humans.

In vitro studies indicate that FFA compete with glucose as an oxidative fuel in muscle and, in addition, stimulate gluconeogenesis in liver. During counterregulation of hypoglycemia, plasma FFA increase and this is associated with an increase in glucose production and a suppression of glucose utilization. To test the hypothesis that FFA mediate changes in glucose metabolism that occur during counterregulation, we examined the effects of acipimox, an inhibitor of lipolysis, on glucose production and utilization ([3-3H]glucose), and incorporation of [U-14C]-alanine into glucose during insulin-induced hypoglycemia. Eight normal volunteers were infused with insulin for 8 h to produce modest hypoglycemia (approximately 3 mM) on two occasions, first without acipimox (control) and then with acipimox administration (250 mg per os at 60 and 240 min). Despite identical plasma insulin concentrations, glucose had to be infused in the acipimox experiments (glucose-clamp technique) to maintain plasma glucose concentrations identical to those in control experiments. Acipimox completely prevented counterregulatory increases in lipolysis so that during the last 4 h plasma FFA were below baseline values and averaged 67 +/- 13 vs. 725 +/- 65 microM in control experiments, P < 0.001. Concomitantly, overall glucose production was reduced by 40% (5.5 +/- 11 vs. 9.3 +/- 0.7 mumol/kg per min, P < 0.001), and gluconeogenesis from alanine was reduced by nearly 70% (0.32 +/- 0.09 vs. 1.00 +/- 0.18 mumol/kg per min, P < 0.001), while glucose utilization increased by 15% (10.8 +/- 1.4 vs. 9.3 +/- 0.7 mumol/kg per min). We conclude that FFA play a critical role in mediating changes in glucose metabolism during counterregulation, and that under these conditions, FFA exert a much more profound effect on hepatic glucose production than on glucose utilization.     

CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats

OBJECTIVE: To evaluate effects of CordyMax trade mark Cs-4, a mycelial fermentation product of Cordyceps sinensis, on improving glucose metabolism and insulin sensitivity. DESIGN: An in vivo pharmacology study. Subjects and Study Interventions: Adult Wistar rats, male and female, were given CordyMax 250 or 500 mg/kg per day or placebo for 17 days by gavage. OUTCOME MEASUREMENTS: Fasting blood glucose, fasting plasma insulin, glucose-insulin index, and oral glucose tolerance. RESULTS: Rats fed Cs-4 at either 250 or 500 mg/kg showed significantly reduced fasting blood glucose after the 17-day treatment, by 27% and 24% from baselines respectively (both p < 0.001). Examination of fasting plasma insulin demonstrated a 37% decrease in the high dose treatment groups (p = 0.012). Glucose-insulin index, an index of insulin sensitivity, increased by 10% and 17% in both 250 and 500 mg/kg groups (p = 0.008 and p = 0.0001, respectively). Oral glucose tolerance tests showed significantly improved glucose tolerance at 0.5, 1.0, and 2.0 hours after oral administration of a bolus of glucose (the area under the glucose curve: p = 0.05-0.006), but no change at 5 hours. CONCLUSION: CordyMax Cs-4 is effective in lowering basal blood glucose and plasma insulin, improving glucose metabolism by enhancing insulin sensitivity, and improving oral glucose tolerance.     

甲泼尼龙抑制神经干细胞并诱导其凋亡的研究

目的：研究甲泼尼龙对体外培养的神经干细胞的直接作用，为有效的结合这两种治疗方法提供依据和指导。方法：体外培养神经干细胞，加入MP培养12h、24h和48h后，用细胞活性检测试剂CCK-8，检测其对神经干细胞活性的影响，用Hoeehst 33258染色观察细胞凋亡，用Annexin V／PI双染色法检测神经干细胞凋亡比率。结果：甲泼尼龙对体外培养的活性有抑制作用，而且可以诱导体外培养的神经干细胞的发生凋亡。结论：甲泼尼龙不利于神经干细胞的生长，不宜在进行甲泼尼龙冲击疗法的同时进行神经干细胞移植。     

Comparative study of early metabolic events resulting from the administration of the two diabetogenic agents alloxan and streptozotocin

Abstract In this study it was demonstrated that comparable doses of streptozotocin and alloxan produced similar degrees of pancreatic insulin depletion 48 hours after intravenous injection into rats. The metabolic status of animals injected with either streptozotocin (65 mg/kg) or alloxan (60 mg/kg) was assessed prior to and 24 and 48 hours after injection. Metabolic changes consistent with the induction of acute diabetes were observed after both agents. No qualitative differences were revealed between the responses to the two drugs as reflected by plasma glucose, FFA, glycerol and triglyceride responses and by changes in FFA and glycerol release in vitro. This applied whether the animals were fed ad libitum or were restricted to glucose as the sole caloric source. These results indicate that potential extrapancreatic toxic effects of alloxan and streptozotocin do not significantly interfere with the acute diabetic metabolic changes induced by these agents and that these changes, over the first 48 hours, were primarily a consequence of β-cell destruction and insulin deficiency. —- Comparison of the effects of the differing dietary regimes indicates that both endogenous and exogenous triglyceride contribute to the hypertriglyceridaemia of the acute diabetes induced by both agents. Higher plasma triglyceride concentrations were observed in streptozotocin than in alloxan treated animals fed a free diet but this difference was not evident when the diet was replaced by glucose. Such quantitative differences in the metabolic responses to the two agents could be explained on the basis of the observed variation in the rate of pancreatic insulin depletion and/or variations in food intake.     

Operation of the "Glucose-Fatty Acid Cycle" during Experimental Elevations of Plasma Free Fatty Acid Levels in Man

Abstract. In order to determine whether increased plasma free fatty acid (FFA) levels inhibit glucose utilization in man, glucose metabolism was studied in 8 normal subjects both under basal conditions and during experimental elevations of plasma FFA concentrations induced by the administration of high fat meals and heparin. A primed constant infusion of 1-¹⁴C-glucose was used to measure the rate of turnover, the fractional removal rate and the rate of oxidation of plasma glucose under both experimental conditions. Elevations of FFA levels (+117%) were accompanied by a 9% reduction in both the fractional removal rate of glucose and the hepatic glucose production so that glycaemia remained unchanged. The % glucose converted to CO₂ and the % CO₂ derived from plasma glucose decreased respectively by 13.5% and 21.7%, while unlabelled CO₂ production remained unchanged. This reduction in glucose utilization occurred despite a significant rise in insulin concentration indicating that high FFA levels reduce sensitivity to insulin. The tissue implicated in the inhibitory effect of FFA on overall glucose utilization cannot be determined from these experiments but it is suggested that muscle participated in these metabolic changes. These data provide further arguments supporting the view that plasma FFA participate in the regulation of glucose metabolism in man.     

Mechanistic modeling of the effects of glucocorticoids and circadian rhythms on adipokine expression

A mechanism-based model was developed to describe the effects of methylprednisolone (MPL), circadian rhythms, and the glucose/free fatty acid (FFA)/insulin system on leptin and adiponectin expression in white adipose tissue in rats. Fifty-four normal Wistar rats received 50 mg/kg MPL intramuscularly and were sacrificed at various times. An additional set of 54 normal Wistar rats were sacrificed at 18 time points across the 24-h light/dark cycle and served as controls. Measurements included plasma MPL, glucocorticoid receptor (GR) mRNA, leptin mRNA, adiponectin mRNA, plasma leptin, adiponectin, glucose, FFA, and insulin. MPL pharmacokinetics was described by a two-compartment model with two absorption components. All measured plasma markers and mRNA expression exhibited circadian patterns except for adiponectin and were described by Fourier harmonic functions. MPL caused significant down-regulation in GR mRNA with the nadir occurring at 5 h. MPL disrupted the circadian patterns in plasma glucose and FFA by stimulating their production. Plasma glucose and FFA subsequently caused an increase in plasma insulin. Furthermore, MPL disrupted the circadian patterns in leptin mRNA expression by stimulating its production. This rise was closely followed by an increase in plasma leptin. Both leptin mRNA and plasma leptin peaked at 12 h after MPL and eventually returned back to their circadian baselines. MPL and insulin had opposing effects on adiponectin mRNA expression and plasma adiponectin, which resulted in biphasic pharmacodynamic profiles. This small systems model quantitatively describes, integrates, and provides additional insights into various factors controlling adipokine gene expression.     

Substrate Turnover during Prolonged Exercise in Man: SPLANCHNIC AND LEG METABOLISM OF GLUCOSE, FREE FATTY ACIDS, AND AMINO ACIDS

Arterial concentrations and substrate exchange across the leg and splanchnic vascular beds were determined for glucose, lactate, pyruvate, glycerol, individual acidic and neutral amino acids, and free fatty acids (FFA) in six subjects at rest and during 4 h of exercise at approximately 30% of maximal oxygen uptake. FFA turnover and regional exchange were evaluated using (14)C-labeled oleic acid.The arterial glucose concentration was constant for the first 40 min of exercise, but fell progressively thereafter to levels 30% below basal. The arterial insulin level decreased continuously, while the arterial glucagon concentration had risen fivefold after 4 h of exercise. Uptake of glucose and FFA by the legs was markedly augmented during exercise, the increase in FFA uptake being a consequence of augmented arterial levels rather than increased fractional extraction. As exercise was continued beyond 40 min, the relative contribution of FFA to total oxygen metabolism rose progressively to 62%. In contrast, the contribution from glucose fell from 40% to 30% between 90 and 240 min. Leg output of alanine increased as exercise progressed.Splanchnic glucose production, which rose 100% above basal levels and remained so throughout exercise, exceeded glucose uptake by the legs for the first 40 min but thereafter failed to keep pace with peripheral glucose utilization. Total estimated splanchnic glucose output was 75 g in 4 h, sufficient to deplete approximately 75% of liver glycogen stores. Splanchnic uptake of gluconeogenic precursors (lactate, pyruvate, glycerol, alanine) had increased 2- to 10-fold after 4 h of exercise, and was sufficient to account for 45% of glucose release at 4 h as compared to 20-25% at rest and at 40 min of exercise. In the case of alanine and lactate, the increase in precursor uptake was a consequence of a rise in splanchnic fractional extraction.It is concluded that during prolonged exercise at a low work intensity (a) blood glucose levels fall because hepatic glucose output fails to keep up with augmented glucose utilization by the exercising legs; (b) a large portion of hepatic glycogen stores is mobilized and an increasing fraction of the splanchnic glucose output is derived from gluconeogenesis; (c) blood-borne substrates in the form of glucose and FFA account for a major part of leg muscle metabolism, the relative contribution from FFA increasing progressively; and (d) augmented secretion of glucagon may play an important role in the metabolic adaptation to prolonged exercise by its stimulatory influence on hepatic glycogenolysis and gluconeogenesis.     

Effect of synthetic human glucose-dependent insulinotropic polypeptide (hGIP) on the release of insulin in man

During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose-dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg-1 min-1 for 30 min and 0.5 pmol kg-1 min-1 for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92 +/- 18 pmol 1(-1) to 257 +/- 42 pmol 1(-1) 60 min after ingestion of glucose (mean +/- SEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 +/- 67 vs. 200 +/- 48 pmol 1(-1); P less than 0.02; 465 +/- 96 vs. 207 +/- 48 pmol 1(-1); P less than 0.01). However, the total and incremental integrated insulin responses during the first 60 min of the study were, though lower, not significantly different from the oGTT experiment when glucose and hGIP were infused simultaneously. Thus, in the presence of mild physiological hyperglycaemia, human GIP is able to enhance the initial insulin response almost equivalently to the stimulus provided by oral glucose. Decreased insulin concentrations during porcine GIP infusions in previous experiments might be due to sequence differences between human and porcine GIP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assay-dependent variability of serum insulin levels during oral glucose tolerance test: influence on reference intervals for insulin and on cut-off values for insulin sensitivity indices.

BACKGROUND: The oral glucose tolerance test (oGTT) is the most common method to estimate indices of insulin sensitivity in clinical as well as in epidemiological studies. The aim of this study was to investigate the variability of insulin levels for reference intervals and of insulin sensitivity indices during oGTT by three different insulin immunoassays. METHODS: Serum insulin levels were determined during oGTT of randomly selected adult subjects (total n=101, with n=68 with normal glucose tolerance) by the LIAISON (LIA), the Elecsys (EL) and the AutoDELFIA (AD) method. RESULTS: Sensitivity and precision of all three insulin assays were comparable. Insulin levels demonstrated a close (p<0.001) interassay correlation (LIA vs. EL: r=0.987, LIA vs. AD: r=0.966, EL vs. AD: r=0.965). Insulin levels and insulin sensitivity indices (n=68) of the AD method were significantly different compared to the LIA or EL assay (p<0.001). Basal insulin levels demonstrated an assay-dependent significant body mass index (BMI) dependency (LIA: r=0.24, p=0.05; AD: r=0.44, p<0.001; EL: r=0.36, p<0.01) in the regression analysis. At 120 min post glucose, gender was the relevant influencing factor on insulin levels of the LIA (r=0.40, p<0.001), AD (r=0.37, p<0.01) and EL (r=0.40 p<0.001) method. CONCLUSIONS: We conclude that assay-dependent reference intervals should be used for the clinical interpretation of insulin levels from oGTT and of insulin sensitivity indices. Moreover, BMI and gender have to be considered as influencing factors.     

Increased plasma cyclic AMP concentrations in fasting man

Plasma concentrations of adenosine 3′, 5′ monophosphate (cyclic AMP), free fatty acids (FFA), glycerol and glucose were measured after 24, 48 and 72 h fasting in healthy male students. There was a marked rise in plasma concentrations of cyclic AMP, FFA and glycerol from 24 to 48 h fasting with no further changes from 48 to 72 h fasting. Plasma glucose concentrations fell. After 72 h fasting, inhibition of adipose tissue lipolysis with a nicotinic acid analogue effected no significant change in plasma cyclic AMP concentrations, indicating that the elevated plasma nucleotide concentrations during fasting were not related to stimulation of lipolysis.