A comparison of octreotide delivered by continuous subcutaneous infusion with intermittent injection in the treatment of acromegaly

This study was undertaken to evaluate GH, IGF1 and drug levels during incremental continuous subcutaneous infusion of octreotide and compare these parameters following long-term treatment of 300 micrograms 24 h-1 by intermittent injection in a group of acromegalic patients. Ten patients were treated by continuous subcutaneous infusion in increasing dose from 200 micrograms 24 h-1 to 1600 micrograms 24 h-1; this resulted in consistent 24-h growth hormone suppression (less than 5.0 mU l-1), and normalisation of IGF1; the optimum dose was 400 micrograms 24 h-1, the maximum dose was tolerated without any untoward effects. There was no deterioration in carbohydrate tolerance despite a marked decrease in fasting and stimulated insulin levels. After 1 year of maintenance treatment, 300 micrograms 24 h-1 by intermittent injection, patients were re-evaluated; GH levels were not so consistently suppressed over the 24-h period and carbohydrate tolerance had deteriorated. A sub-group of patients with sub-optimal GH suppression on this regimen were identified and reassessed after 6 weeks treatment with an increased dose, 600 micrograms 24 h-1 by intermittent injection; both mean GH suppression and carbohydrate tolerance improved. The dose of drug and method of administration is best adjusted for each patient to achieve optimum GH suppression, thereby minimise compensatory hyperinsuliaemia and hopefully reduce morbidity and mortality. Alterations in pituitary tumour size and acquisition of gallstones during treatment have been observed which substantiate the need to re-evaluate these parameters on routine follow-up of acromegalic patients on long-term octreotide.     

Renal extraction of insulin and C‐peptide in man before and after a glucose meal

It was recently shown that the early rise in arterial insulin concentration after an oral glucose meal is largely because of a decreased extraction of the hormone. The kidney is a major site for extraction of insulin and C‐peptide. We therefore measured the renal extraction of insulin and C‐peptide in eight healthy individuals before and after ingestion of 75 g of glucose. Arterial, renal venous and hepatic venous catheters were inserted. Splanchnic and renal plasma flow were measured, as well as arterial, hepatic venous and renal venous concentrations of insulin and C‐peptide. Renal fractional extraction of insulin increased significantly, from 21% to a maximum of 48% after the meal while the renal fractional extraction of C‐peptide did not change significantly. Renal blood flow decreased slightly but significantly after the meal. It is concluded that renal fractional extraction of insulin increases and that renal blood flow decreases after a glucose meal.     

互动式教育在规范社区老年糖尿病患者胰岛素注射中的研究

目的　评价互动式教育在规范社区老年糖尿病患者胰岛素注射中的应用效果。方法 采用便利抽样法选取上海市某社区行笔型胰岛素注射的老年糖尿病患者150例,随机分为对照组和干预组各80例。对照组给予常规教育指导;观察组在对照组基础上组成的互动式健康教育团队。两组患者分别于教育前、教育6个月后采用胰岛素规范注射的知信行问卷调查,评价两组患者胰岛素注射相关知识、技能的掌握程度。评估其干预后糖代谢水平和低血糖的发生率,观察这种服务模式的可行性。 结果 干预前两组患者胰岛素知识和技能、糖化血红蛋白值、低血糖的发生率差异无统计学意义(P＞0.05)。干预6月观察组较对照组糖化血红蛋白值下降更为显著(P<0.05),观察组胰岛素知识和技能提高更为显著(P<0.05)。观察组低血糖发生率较对照组明显下降(P<0.05)。结论 互动式教育规范社区2型糖尿病患者胰岛素注射,改变传统单纯糖尿病知识教育方式,通过患者技能培训和改善生活质量,提高患者自我管理技能。     

Identification,characterization and expression of a defensin‐like antifungal peptide from the whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae)

Defensins are a class of small and diverse cysteine‐rich proteins which have broad‐spectrum antimicrobial activities. We identified and characterized a full‐length cDNA encoding a putative defensin‐like peptide from the whitefly Bemisia tabaci by RACE and quantitative real‐time (qRT)‐PCR. The full‐length cDNA, named Btdef, was 388 bp long and contained an open reading frame of 228 bp. The putative mature Btdef had 46 amino acids with a molecular weight of 5.06 kDa. The deduced amino acid sequence showed significant homology with insect defensins from Heliothis virescens (76%) and Galleria mellonella (75%). The predicted mature form of Btdef was expressed as a recombinant peptide in Escherichia coli. Antimicrobial assays of the purified product indicated that Btdef was most active against fungi. qRT‐PCR analyses indicated that Btdef mRNA was constitutively expressed in different tissues of B. tabaci, including fat body, midgut, ovaries and salivary gland, and was induced by fungal infection. Btdef mRNA expression was also significantly altered after feeding on different host plants, indicating that diet affects immune defences in B. tabaci. These results describe for the first time the basic properties of a defensin‐like peptide from B. tabaci that probably plays an important role in the immune response against pathogens.     

IGF-1, IGFBP-3, VEGF and MMP-9 levels and their potential relationship with renal functions in patients with compensatory renal growth

BACKGROUND: Mechanisms of compensatory renal growth (CRG) still remain a mystery. Various growth factors, including growth hormone, insulin-like growth factor-1 (IGF-1) have been implicated in different forms of CRG. AIMS: To investigate the serum levels of IGF-1, vascular endothelial growth factor (VEGF - role in vascular remodelling), matrix metalloproteinase-9 (MMP-9 - essential for normal nephrogenesis) and correlation of renal function in patients with unilateral nephrectomized, agenesis and hypoplasic kidney. METHODS: Thirty patients were included in this study. In group I, there were 10 patients with unilateral nephrectomy, while in group II, there were 10 patients with unilateral agenesis. As for group III, there were 10 patients with unilateral hypoplastic kidney. The serum levels of IGF-1, IGF-binding protein-3 (IGFBP-3), VEGF and MMP-9 were studied in all the cases. Clearance of creatinin (Ccr) and protein excretion were examined in the 24 h urine. CRG was determined with ultrasonography and scintigraphy. Twenty-six control subjects were also studied. RESULTS: The levels of IGF-1, IGFBP-3, VEGF and MMP-9 were significantly higher in patients than in the control subjects (P < 0.001). Ccr and protein excretion levels were different in study groups than in those of the control group (P < 0.01). There were positive correlations between the serum levels of IGF-1 with IGFBP-3; IGF-1 with MMP-9; IGFBP-3 with MMP-9 (r = 0.825, P = 0.0001; P < 0.001 r = 0.611; P < 0.001 r = 0.585, respectively). There were negative correlations between GFR and the serum levels of IGF-1, IGFBP-3 and MMP-9 (P < 0.01 r = -0.708; P = 0.002 r = -0.803; P < 0.05 r = -0.442, respectively). Furthermore, there were positive correlations between proteinuria and the serum levels of IGF-1, IGFBP-3 and MMP-9 (P = 0.039 r = 0.600; P < 0.05 r = 0.456; P < 0.05 r = 0.424). CONCLUSIONS: Increased IGF-1, IGFBP-3, VEGF and MMP-9 were observed in CRG in the follow-up period. IGF-1 and MMP-9 seemed to have increased in patients with CRG in defiance of the development of fibrosis. Moreover, IGF-1 and MMP-9 seem to be associated with reduced renal function and proteinuria.     

IGF‐I concentrations are positively associated with carotid artery atherosclerosis in women

BACKGROUND. Alterations in the growth hormone (GH)/insulin‐like growth factor I (IGF‐I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF‐I levels.

AIMS. To investigate whether IGF‐I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery.

METHODS. Fasting plasma IGF‐I concentrations (n = 1008) were measured in a large population‐based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method.

RESULTS. Low IGF‐I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C‐reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF‐I concentrations were positively associated with the mean IMT of women (ß = 0.127, P = 0.009) whereas the association in men was weaker and negative (ß = ?0.088, P = 0.034). The 1169A allele was associated with low low‐density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women.

CONCLUSIONS. IGF‐I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF‐I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.     

Glucose tolerance, plasma insulin and α-lipoproteins in young male myocardial infarction survivors compared with controls matched on serum cholesterol concentration

Abstract. In order to identify metabolic risk factors other than hypercholesterolaemia, all cases of acute myocardial infarction, diagnosed in males aged under 40 years, were studied over a period of 6 years in Göteborg, Sweden. Twenty out of twenty-four patients who were alive at the time of the study were compared with forty controls matched for serum cholesterol concentration. A previous report has noted lower apolipoprotein A (apoA) and a higher α-lipoprotein triglyceride concentration in these young myocardial infarction patients compared with the matched controls. Basal blood glucose, oral glucose tolerance and plasma insulin levels did not differ between the patients and controls, i.e. decreased glucose tolerance and elevated plasma insulin levels were not found to be additional risk factors for myocardial infarction in young males if serum cholesterol concentration was taken into consideration. This finding could be explained by the fact that patients and controls were all high cholesterol individuals and a difference between the patients and the general population is still possible. Low apoA was a risk factor independent of serum cholesterol as well as glucose intolerance and elevated plasma insulin levels.     

Effects of burn injury on insulin secretion and on sensitivity to insulin in the rat in vivo.

Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non-lethal 20 percent dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1-0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1-0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p less than 0-02) in scalded (mean 3-9 percent min.(-1) than in control rats (mean 6-3 percent min.(-1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 125I-labelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.     

Effects of Burn Injury on Insulin Secretion and on Sensitivity to Insulin in the Rat in vivo

Abstract. Both insulin resistance and impairment of insulin secretion are know to occur in man after injury. The relative importance of these effects was studied in rats 2 h after a non-lethal 20 % dorsal scald. No impairment of insulin secretion was found after this injury. Concentrations of both blood glucose and plasma insulin were elevated in scalded rats. Scalded rats responded to intravenous glucose injection (1. 0 g/kg) with a further rise in plasma insulin concentration, which remained normal for the prevailing blood glucose concentration. However, marked impairment of glucose tolerance was observed, indicating the presence of insulin resistance. After intravenous insulin injection (1. 0 U/kg) the initial rate coefficient for fall of blood glucose concentration was significantly lower (p < 0–02) in scalded (mean 3. 9 % min. ^-1) than in control rats (mean 6–3 % min. ^-1). The minimum in blood glucose concentration after insulin injection was reached at 10 min. in control rats, but not until 60 min. after injection in scalded rats. This difference was due to a delay in compensation for the hypoglycaemia in the scalded rats, since the rate of disappearance of insulin measured by injection of a tracer of 25i-labelled bovine insulin was not decreased after this injury. It was concluded that the impairment of glucose utilization in scalded rats (Heath and Corney, 1973) is due to decreased sensitivity to insulin rather than to suppression of insulin release.     

The glucose-induced gastrointestinal stimulation of insulin secretion in man: relation to age and to gastrin release.

An oral 50 g glucose tolerance test and a simple intravenous glucose infusion test were performed in 20 young (20 - 32 years), 20 middle-aged (42 -55 years), and 20 old (65 - 81 years) normal subjects. Blood glucose, serum insulin, and serum gastrin concentrations were measured during all tests. The intravenous glucose infusion duplicated the oral blood glucose curve in young, middle-aged, and half of the old subjects. In the remaining old subjects the intravenous blood glucose curve was below the oral blood glucose curve. Glucose and insulin concentrations were of similar magnitude in all groups, but maximum concentrations were reached later in the old subjects. Glucose per os induced a rapid rise in serum gastrin concentrations of the order of 10 pmol/1 and a subsequent decrease of about 20 pmol/1 in all groups. The intravenous glucose infusion induced no significant changes in serum gastrin concentrations. The non-glycaemic (i.e. enteral) stimulation of insulin secretion was expressed as the difference between the integrated incremental areas of the oral and intravenous insulin curves in subjects with identical glucose curves during the two tests. This stimulation was of similar magnitude in all age groups, and it was not correlated to variations in gastrin concentrations. However, in the young subjects the enteral stimulation was greater during the first 30 minutes and smaller during the two last hours when compared to the old subjects. The results suggest that: 1. A simple intravenous glucose infusion test can be used to copy the oral blood glucose curve. 2. The size of the enteral stimulation of insulin secretion during the whole test is independetn of age. 3. The action of the glucose-induced enteral stimulation is delayed with age, and closely linked to the dynamics of the glycaemic stimulus. 4. The glucose-induced gastrin release is probably too small to affect insulin secretion significantly.     

The Glucose-Induced Gastrointestinal Stimulation of Insulin Secretion in Man: Relation to Age and to Gastrin Release

Abstract. An oral 50 g glucose tolerance test and a simple intravenous glucose infusion test were performed in 20 young (20–32 years), 20 middle-aged (42–55 years), and 20 old (65–81 years) normal subjects. Blood glucose, serum insulin, and serum gastrin concentrations were measured during all tests. The intravenous glucose infusion duplicated the oral blood glucose curve in young, middle-aged, and half of the old subjects. In the remaining old subjects the intravenous blood glucose curve was below the oral blood glucose curve. Glucose and insulin concentrations were of similar magnitude in all groups, but maximum concentrations were reached later in the old subjects. Glucose per os induced a rapid rise in serum gastrin concentrations of the order of 10 pmol/1 and a subsequent decrease of about 20 pmol/1 in all groups. The intravenous glucose infusion induced no significant changes in serum gastrin concentrations. The non-glycaemic (i. e. enteral) stimulation of insulin secretion was expressed as the difference between the integrated incremental areas of the oral and intravenous insulin curves in subjects with identical glucose curves during the two tests. This stimulation was of similar magnitude in all age groups, and it was not correlated to variations in gastrin concentrations. However, in the young subjects the enteral stimulation was greater during the first 30 minutes and smaller during the two last hours when compared to the old subjects.
The results suggest that: 1. A simple intravenous glucose infusion test can be used to copy the oral blood glucose curve. 2. The size of the enteral stimulation of insulin secretion during the whole test is independent of age. 3. The action of the glucose-induced enteral stimulation is delayed with age, and closely linked to the dynamics of the glycaemic stimulus. 4. The glucose-induced gastrin release is probably too small to affect insulin secretion significantly.     

Inhibition of muscular amino acid release by lipid infusion in man

Amino acid balances of healthy postabsorptive volunteers were investigated with the forearm technique under the influence of an intravenous infusion of triglyceride emulsions (LCT; MCT/LCT) [corrected]. A decrease of the basal muscular release of most of the amino acids, respectively an increase of pre-existent uptake rates [corrected]. In parallel, arterial concentrations of these amino acids declined. With constant insulin levels and substantially unchanged blood glucose levels, this inhibition of muscular proteolysis and/or stimulation of proteosynthesis is most probably due to the increased level of free fatty acids.     

MicroRNA miR‐8 regulates multiple growth factor hormones produced from Drosophila fat cells

Metabolic organs such as the liver and adipose tissue produce several peptide hormones that influence metabolic homeostasis. Fat bodies, the Drosophila counterpart of liver and adipose tissues, have been thought to analogously secrete several hormones that affect organismal physiology, but their identity and regulation remain poorly understood. Previous studies have indicated that microRNA miR‐8, functions in the fat body to non‐autonomously regulate organismal growth, suggesting that fat body‐derived humoral factors are regulated by miR‐8. Here, we found that several putative peptide hormones known to have mitogenic effects are regulated by miR‐8 in the fat body. Most members of the imaginal disc growth factors and two members of the adenosine deaminase‐related growth factors are up‐regulated in the absence of miR‐8. Drosophila insulin‐like peptide 6 (Dilp6) and imaginal morphogenesis protein‐late 2 (Imp‐L2), a binding partner of Dilp, are also up‐regulated in the fat body of miR‐8 null mutant larvae. The fat body‐specific reintroduction of miR‐8 into the miR‐8 null mutants revealed six peptides that showed fat‐body organ‐autonomous regulation by miR‐8. Amongst them, only Imp‐L2 was found to be regulated by U‐shaped, the miR‐8 target for body growth. However, a rescue experiment by knockdown of Imp‐L2 indicated that Imp‐L2 alone does not account for miR‐8's control over the insect's growth. Our findings suggest that multiple peptide hormones regulated by miR‐8 in the fat body may collectively contribute to Drosophila growth.