以精氨酸负荷试验观察原发性高血压胰岛内分泌功能的变化

对５１例原发性高血压（ＥＨ）患者和３０例对照组进行精氨酸负荷试验，测定铡荷前、后血糖、胰岛素、Ｃ肽、胰高糖素水平。结果显示，ＥＨ患者精氨酸负荷前、后胰岛屿纱和胰主糖素均高于对照组（Ｐ〈０．０５或更小）。负荷前Ｃ肽同于对照组（Ｐ〈０．０５），负荷后与对照组无显著差异。ＥＨ患者胰岛素敏感性指数低于对照组（Ｐ〈０．００１），提示精氨酸负荷后纱升高是清除率下降所致。ＥＨ的胰岛素敏感性下降可能与胰高糖素升高     

Effect of sparteine sulphate upon basal and nutrient-induced insulin and glucagon secretion in normal man

Summary Infusion of a therapeutic dose of sparteine sulphate, increased the basal plasma insulin level and lowered plasma glucose. When an intravenous glucose tolerance test was performed with the infusion, the total insulin AUC was significantly larger than in absence of sparteine (2025 vs 1464 µU/ml×min), plasma glucose levels were lower and improved glucose utilization was observed (k_g:1.55 vs 1.39%). In the presence of arginine, sparteine sulphate stimulated both and cells, increasing both the total insulin (1907 vs 1516 µU/ml×minp<0.02) and total glucagon AUCs (7616±654 vs 6789±707 pg/ml×minp<0.01). Thus, sparteine sulphate increased both basal and nutrient-induced insulin and glucagon secretion in normal man.This work was presented in part at the XII Congress of the International Diabetes Federation, Madrid, 23–28/9/1985     

Effects of a new diuretic piretanide on glucose tolerance,insulin secretion and 125I-insulin binding

Summary The effect of a new diuretic, piretanide, on glucose tolerance, insulin secretion and ¹²⁵I-insulin binding to erythrocytes was studied in 12 male patients with mild essential hypertension. After a 4 week wash-out period with placebo, piretanide 6 mg b.i.d. was administered in a single-blind manner for 8 consecutive weeks. Although glucose tolerance deteriorated slightly in one patient, the diuretic treatment had no effect on the mean blood glucose concentrations during oral glucose tolerance tests or on glyco-haemoglobin A₁ measurements, both studies being done at 4 week intervals. Preservation of euglycemia was associated with increased insulin secretion. After 8 weeks of piretanide therapy the basal C-peptide concentration was 61% higher than the pretreatment level (0.44 vs 0.71 µU/ml; p<0.05). Glucagon — stimulated C-peptide concentrations were significantly elevated after 4 (1.67 vs 2.53 µU/ml, p<0.05) and after 8 weeks (1.67 vs. 2.90 µU/ml, p<0.01) of diuretic treatment. Fasting plasma immunoreactive insulin (IRI) levels were virtually unchanged by the drug therapy. The enhanced insulin secretion did not appear secondary to increased insulin resistance at the insulin receptor level, since the specific bound fraction of ¹²⁵I-insulin remained unaffected by diuretic treatment. Although short-term loop diuretic treatment appears to have no effect on glucose tolerance, the very low density lipoprotein synthetic rate may be promoted by the increased insulin secretion.     

新发2型糖尿病患者早期胰岛素强化治疗临床疗效分析

目的：评价新发2型糖尿病患者早期胰岛素强化治疗的效果。方法：对28例新发2型糖尿病患进行早期胰岛素强化治疗。结果：空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbAlc）水平均显著下降（P〈0．01）,而空腹C肽水平增高（P〈0．05）,餐后2hC肽水SF（2hCP）明显升高（P〈0．01）。结论：早期胰岛素强化治疗能尽快解除高糖毒性,胰岛B细胞功能显著恢复,减轻糖毒性。     

Insulin secretion and glucose tolerance in non-insulin dependent diabetic patients after chronic nifedipine treatment

Summary The effect of nifedipine 40 mg·day^–1 for 3 months on glucose tolerance, insulin and C-peptide secretion after an oral glucose tolerance test (OGTT), intra-venous glucose tolerance test (IVGTT) and glucagon stimulatory test, has been studied in 8 moderately hypertensive women suffering from non-insulin dependent diabetes mellitus (NIDDM).No significant variation in glucose metabolism was noted after nifedipine treatment, except for a slight improvement in insulin secretion after OGTT at the end of the study. There was an increase in cholesterol as a collateral effect.     

非酒精性脂肪肝患者口服葡萄糖后血浆胰高血糖素样肽和葡萄糖依赖性促胰岛素多肽水平的变化

目的 考察非酒精性脂肪肝(nonalcoholic fatty liver,NAFLD)患者口服葡萄糖后胰高血糖素样肽(glucagon- likepeptide-1,GLP-1)和葡萄糖依赖性促胰岛素多肽(glucose-dependent insulinotropic ploypeptide,GIP)分泌的特征。方法 选取34例非酒精性脂肪肝和42例健康人群,行口服糖耐量试验后在120 min内测定血GLP-1、GIP、血糖、血胰岛素、胰高血糖素含量进行比较。结果 NAFLD患者经葡萄糖诱导后GLP-1分泌量明显低于正常对照组(P<0.01),而GIP没有明显改变,但是所有患者均存在胰岛素抵抗。与正常对照组相比,NAFLD患者空腹胰岛素水平和葡萄糖诱导后的胰岛素水平均明显升高,血糖降低缓慢,而空腹胰高血糖素水平明显升高。结论 NAFLD患者经葡萄糖诱导分泌GLP-1功能缺陷,GIP分泌无异常。NAFLD患者存在胰岛素抵抗、高胰岛素血症和胰高血糖素血症。     

Long term treatment of moderate hypertension with penbutolol (Hoe 893d) III. Effects on glucose tolerance and insulin production

Summary Studies in seven patients with moderate hypertension were done to explore the effect of the non-selective beta-receptor blocking agent penbutolol on blood glucose and plasma insulin levels under fasting conditions, and following a glucose load. Oral penbutolol 20–30 mg, twice daily for 3–8 months, produced no change in fasting levels of blood glucose and plasma insulin, or in the blood glucose response following an oral or iv glucose load. The initial insulin response to intravenous glucose was similar before and during penbutolol treatment. The total integrated insulin response following iv glucose increased slightly during treatment when measured from insulin zero level, but was unaltered when calculated from the initial basal insulin level. Following oral glucose the total integrated insulin response was not affected by treatment with penbutolol.     

Effect of chlorpromazine on blood glucose and plasma insulin in man

Summary In three groups of normal subjects and in one group of patients with latent diabetes mellitus a study has been made of the effects of chlorpromazine (CPZ) on blood glucose and plasma insulin. CPZ 75 mg/day for 7 days did not alter the plasma insulin response after oral glucose; nor did CPZ 50 mg/day for 7 days affect the glucose assimilation rate or insulin response to glucose injection. Infusion of CPZ 50 mg in 60 min slightly increased the basal blood glucose level but had no significant effect on basal plasma insulin. The insulin/glucose ratio after the end of the infusion was significantly higher than during the period of infusion of the drug. In latent diabetic patients CPZ infusion significantly diminished the insulin/glucose ratio during an intravenous glucose tolerance test. These results suggest that, whereas prolonged treatment with low doses of CPZ did not modify glucose tolerance and glucose-stimulated pancreatic response, higher acute doses of the drug may induce hyperglycaemia and can inhibit insulin secretion both in normal man and in patients with latent diabetes mellitus.     

Effects of pirenzepine on plasma insulin,glucagon and pancreatic polypeptide levels in normal man

Summary The secretion of various pancreatic hormones (insulin, glucagon and pancreatic polypeptide) is affected to a different extent by the cholinergic system. In 7 healthy subjects the effects of treatment for 1 week with pirenzepine, an anticholinergic drug selective for muscarinic receptors, on basal secretion of these hormones and on that induced by i.v. glucose (IVGTT) and arginine were evaluated. The drug did not reduce basal levels of insulin and glucagon whereas it caused an appreciable reduction in basal pancreatic polypeptide (PP). The responses of insulin and blood glucose to IVGTT and to arginine were not changed by treatment, nor was that of plasma glucagon to arginine. The infusion of arginine did induce an increase in PP level, which reached a statistically significant maximum at 90 min. This response was not particularly different after administration of pirenzepine. Thus, the results confirm the finding that arginine stimulates PP secretion in vivo and that pirenzepine reduces the basal level of the hormone, whereas it did not appear to affect the response to arginine. The findings exclude any direct action of the drug on insulin or glucagon secretion or on glucose metabolism in general.     

槲皮苷对原发性糖尿病大鼠血糖的作用研究

摘 要 目的：研究槲皮苷对糖尿病大鼠血糖的作用。方法: 选择原发性糖尿病大鼠模型（GK）,将其分为槲皮苷组、格列齐特组、二甲双胍组、空白组、正常组（Wistar大鼠）。分别给与药物干预,空白组与正常组给与生理盐水。2周后,观察GK体质量、进食量、空腹血糖、糖耐量、空腹C肽等指标,观察槲皮苷对于2型糖尿病大鼠血糖的影响。结果: 给药后,槲皮苷组和二甲双胍组大鼠体质量呈进行性下降(P<0.05),且明显低于其他组(P<0.05)。二甲双胍与格列齐特组进食量不断减少(P<0.05),且明显低于其他组(P<0.05)。槲皮苷组大鼠给药2周后空腹血糖较前改善明显（P<0.05）,显著低于空白组（P<0.05）,但空腹血糖改善作用弱于二甲双胍与格列齐特组（P<0.05）。槲皮苷组大鼠给药后糖耐量较前有显著改善(P<0.05),明显优于空白组(P<0.05)。给药2周后,槲皮苷组大鼠C肽水平较前有明显升高（P<0.05）,且显著高于空白组（P<0.05）;槲皮苷组大鼠C肽水平低于格列齐特组（P<0.05）,而与二甲双胍组基本相当（P>0.05）。结论:槲皮苷能显著降低GK大鼠体质量及空腹血糖,改善糖耐量异常,升高空腹C肽水平。揭示槲皮苷对于糖尿病大鼠存在降血糖作用。且其作用机制可能与促进胰岛素分泌,改善胰岛素抵抗有关。     

Lack of effect of intravenous metformin on plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in non-diabetic subjects

A study was carried out to evaluate the acute effect of an intravenous injection of metformin on the fasting plasma concentrations of glucose, insulin, C-peptide, glucagon and growth hormone in 15 non-diabetic subjects. Metformin (1 g) was administered as a bolus in a peripheral vein and blood was sampled 2, 5, 10, 15 and 30 minutes after the drug injection. No significant change in fasting concentration of glucose nor in C-peptide, insulin, glucagon and growth hormone fasting levels was noticed. It is concluded that metformin does not possess an acute direct hypoglycaemic effect in non-diabetic subjects and does not acutely affect the basal activity of endocrine pancreas and pituitary gland in releasing insulin, glucagon and growth hormone.     

Insulin secretion, clearance and sensitivity in black pregnant and non-pregnant women in Harare, Zimbabwe.

OBJECTIVE: To assess whether reported gestational differences in glucose tolerance in Caucasian and Black women could be due to alterations in insulin secretion, clearance or sensitivity. DESIGN: Cross sectional survey. SETTING: Antenatal Clinic, Harare; Department of Medical Laboratory Sciences, University of Zimbabwe. SUBJECTS: 90 healthy women in all the trimesters of pregnancy and 30 healthy non-pregnant women of reproductive age. MAIN OUTCOME MEASURES: Fasting (basal) plasma insulin, C-peptide and glucose concentration. Fasting plasma C-peptide, C-peptide to insulin ratio and glucose to insulin ratio were used as indices of insulin secretion, hepatic insulin clearance and insulin sensitivity respectively. RESULTS: Not all means of the fasting plasma glucose levels amongst the four groups of women were equal (p < 0.001), with all possible comparisons being significant except for the first and second trimester groups. Among the comparisons of the means of the glucose:insulin ratio in the four groups of women, only the means of the first and second trimester women differed (mean difference = 0.23, honestly significance difference = 0.20). All groups were comparable in the means of plasma insulin, C-peptide levels and the C-peptide:insulin ratio. CONCLUSION: Since fasting plasma insulin, C-peptide and C-peptide:insulin ratio were not significantly altered in all trimesters of pregnancy, these data suggest normal basal insulin secretion and clearance during gestation in these sub-Saharan African women.     

Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes

1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM). 2. Fifty-nine T2DM patients with glycosylated haemoglobin (HbA1c) levels between 7.0% and 10.9% were recruited to the present study. Biochemical information and CGM parameters were collected at baseline and after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea + an α-glucosidase inhibitor or insulin + metformin combination therapy). 3. Compared with baseline, serum osteocalcin increased significantly (P = 0.014), whereas parameters related to glucose variability, including the mean amplitude of glycaemic excursions (MAGE) and the standard deviation of blood glucose values, decreased significantly (P < 0.001) after the 8 week treatment period. At baseline, there was a positive correlation between serum osteocalcin levels and fasting C-peptide levels (P = 0.004) and homeostatic model assessment of β-cell function (P = 0.048), but a negative correlation between serum osteocalcin levels and fasting plasma glucose (P = 0.023), HbA1c (P = 0.020), glycated albumin (P = 0.019) and 24 h mean blood glucose (P < 0.001). Multiple stepwise regression analysis indicated that baseline osteocalcin was the single parameter that best predicted the change in MAGE (β = -0.122; P = 0.039). 4. In conclusion, serum osteocalcin concentrations increased with improved glucose control. High initial osteocalcin levels were associated with subsequent improvements in glucose variability during glucose-lowering treatment.     

The in vivo interaction between gliclazide and glibenclamide and insulin on glucose disposal in the rat.

Many reports suggest that extrapancreatic actions contribute to the antidiabetic effect of sulphonylurea drugs (SUs). In this work, the ability of two SUs, namely, gliclazide and glibenclamide, to augment insulin action was studied in vivo. Both drugs elevated the plasma concentration of immunoreactive insulin (IRI) and lowered the plasma concentrations of glucose and non-esterified fatty acids (NEFA) in normal intact rats. These changes were not reproduced in alloxan-diabetic or eviscerated rats. The actions of insulin on plasma glucose and NEFA were not augmented by gliclazide in alloxan-diabetic rats. Neither gliclazide nor glibenclamide (given acutely and for 30 days) augmented the actions of exogenously administered insulin in reducing plasma glucose or NEFA concentrations in intact or eviscerated animals. It was concluded that these SUs do not produce their acute or chronic effects on blood glucose by augmenting the actions of insulin.     

钙拮抗剂对在体大鼠血糖和血清胰岛素水平的影响

作者观察了钙拮抗剂一异搏定对在体大鼠血糖和血清胰岛素水平的影响,结果表明,异搏定能升高大鼠基础血糖和基础胰岛素水平。另外,在大鼠糖耐量试验中,异搏定能使大鼠对葡萄糖诱导的胰岛素反应降低和延迟,从而导致大鼠的糖耐量降低和糖耐量高峰的后移。     

2型糖尿病患者糖耐量试验与胰岛素释放试验相关性分析

目的 通过对糖耐量试验与胰岛素释放试验相关性研究,探讨其对2型糖尿病的诊断与治疗的临床意义.方法 对248例糖病病患者入院治疗前按其空腹胰岛素水平分为空腹低值组(A组)、空腹低值有峰组(B组)、空腹中值组(C组)、空腹高值组(D组)及44例正常对照组(E组),分别采用Backman LX20已糖激酶法测定空腹、糖耐量试验1、2、3 h的血糖和用美国Backman Asscey化学发光仪测定相应的胰岛素水平.结果 糖尿病患者各组胰岛素水平较正常人群组差异有显著性意义(P＜0.05)或非常显著意义(P＜0.01),A组、B组、C组、E组其血糖水平与相应的胰岛素水平具有正相关性,D组血糖水平与相应的胰岛素水平无相关性.结论 2型糖尿病患者在治疗前做糖耐量试验(OGTT)与胰岛素释放试验对其诊断治疗与预后有很重要临床意义.     

空腹血糖受损与糖耐量受损者胰岛素抵抗及胰岛B细胞功能的比较

目的比较空腹血糖受损（IFG）与糖耐量受损者（IGT）胰岛素抵抗及胰岛B细胞功能的不同。方法参照2003年ADA专家委员会建议标准，选择正常糖耐量者（NGT）51例，空腹血糖受损者30例，糖耐量受损者27例。测身高、体质量、血压、血脂及OGTT5点血糖值及胰岛素值。采用HOMA-IR评价IR，HBCI、△I30／△G30、MBCI分别评价基础状态下及糖负荷后的胰岛素分泌功能。结果校正年龄、性别、BMI后，IFG、IGT组HOMA-IR均明显高于NGT人群，差异有统计学意义（P〈0．05）；IGT组HOMA-IR与IFG组比较有下降，但差异无统计学意义。校正年龄等因素后，IFG组HBCI较IGT组降低，差异有统计学意义（P〈0．05）。IGT组MBCI较IFG组降低，差异有统计学意义（P〈0．05）。IGT组△I30／△G30与IFG组比较有下降，但差异无统计学意义。结论空腹血糖受损人群与糖耐量受损人群均存在明显胰岛素抵抗，空腹血糖受损人群主要表现为基础胰岛素分泌缺陷，而糖耐量受损人群为胰岛素早期分泌受损。     

Effect of KAD-1229, a nonsulfonylurea hypoglycemic agent, on plasma glucose and insulin in streptozotocin-induced diabetic dogs

Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.     

Anti-hyperglycaemic action of BRL 26830, a novel beta-adrenoceptor agonist, in mice and rats

BRL 26830, (R*,R*)-(+/-)-methyl 4-[2-[(2-hydroxy-2-phenylethyl)amino] propyl] benzoate, is a new orally active anti-hyperglycaemic agent. In 24 hr-fasted rats and mice, BRL 26830 decreased the blood glucose concentration following the administration of a subcutaneous glucose load. It also improved oral and intravenous glucose tolerance in 24 hr-fasted rats and decreased the post-prandial blood glucose concentration following the consumption of the complete, milk-based, meal "Nutrament". BRL 26830 produced a dose-related increase in the plasma insulin concentration and since it was inactive in lowering blood glucose in streptozotocin-diabetic rats, it is likely that its acute action on glucose tolerance was through the stimulation of insulin secretion. In contrast to the sulphonylurea, glibenclamide, BRL 26830 had no effect on the blood glucose concentration in 5 hr-fasted rats and only produced a transient reduction in 24 hr-fasted rats. BRL 26830 did not improve glucose tolerance when given acutely to hyperinsulinaemic C57BL/6 ob/ob mice. However, chronic treatment of these mice with BRL 26830 for 14-43 days resulted in a significant improvement in glucose tolerance.     

Hormonal counterregulation and consecutive glimepiride serum concentrations during severe hypoglycaemia associated with glimepiride therapy

Objective To examine the release of counterregulatory hormones and consecutive glimepiride serum concentrations during severe hypoglycaemia (SH) associated with glimepiride therapy.Methods In nine type-2 diabetic patients [age 81±9 (65–93) years; diabetes duration 9±4 (3–15) years; initial blood glucose 33±16 (10–54) mg/dl (1.8±0.9 mmol/l); HbA1c 7.2±1.1 (5.6–8.7)%; creatinine clearance 49±33 (15–107) ml/min] who experienced SH associated with glimepiride therapy with neuroglucopenic presentation, insulin, C-peptide, glucagon, epinephrine, norepinephrine, cortisol, adenocorticotrophic hormone (ACTH), human growth hormone (HGH) and pancreatic polypeptide (PP) were determined in blood samples taken at 4-h intervals prior to and during treatment with glucose i.v. Serum from the same samples was screened for sulphonylurea-type oral antidiabetics. Glimepiride concentrations were determined by a validated atmospheric pressure chemical ionization liquid chromatographic-mass spectrometry (APCI-LC-MS) assay.Results Once treatment had begun, normoglycaemia was maintained; most glimepiride levels were below the limit of detection (LOD <0.01 mg/l) and further sulphonylureas could be excluded. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. In addition, protracted marked increases of cortisol and norepinephrine levels were demonstrated. Protracted stimulation of insulin and C-peptide occurred in a period of up to 24 h after SH. No significant protracted responses were observed for ACTH, HGH or PP.Conclusion In SH associated with glimepiride therapy, no correlation between glimepiride serum concentrations and the protracted stimulation of insulin and C-peptide was observed. The secretion of glucagon and epinephrine as counterregulatory hormonal responses was unaffected. Protracted increased release of cortisol might be a medium-term indicator of glimepiride-associated SH.