小檗碱对实验大鼠糖脂代谢的影响

目的探讨小檗碱对实验大鼠胰岛素敏感性和血糖血脂的影响。方法实验大鼠分7组：普食对照组和小檗碱治疗组，高脂对照组和小檗碱治疗组，高脂饮食与极小剂量链脲佐菌素(STZ)诱导的糖尿病对照组，糖尿病小檗碱治疗组和二甲双胍治疗组。疗程为5周。以糖耐量试验评估胰岛功能，以胰岛素耐量试验中的降糖率检测胰岛素敏感性。结果(1)小檗碱使糖尿病鼠的降糖率升高48％，疗效较二甲双胍为好；小檗碱使高脂鼠的胰岛素敏感因子升高78％，延缓了普食鼠降糖率的下降；(2)小檗碱显著降低了高脂大鼠的空腹血糖和负荷血糖；(3)小檗碱使普食鼠、高脂鼠和糖尿病鼠的血清游离脂肪酸分别下调14％、24％和20％，使高脂鼠的血清甘油三酯降低57％。结论小檗碱有显著的胰岛素增敏和降低血清游离脂肪酸的作用，并能降低高脂大鼠的血糖。     

The effect of telmisartan on glucose and lipid metabolism in nondiabetic, insulin-resistant subjects

Intervention studies have shown that angiotensin receptor blocker therapy may reduce the incidence of type 2 diabetes mellitus. It is unknown whether short-term angiotensin receptor blocker therapy can improve glucose and lipid metabolism in insulin-resistant subjects. We evaluated the effect of telmisartan (40 mg/d, 12 weeks) in 20 subjects with insulin resistance (body mass index, 31.8 +/- 3.31 kg/m(2); triglycerides, 179 +/- 98 mg/dL; glucose, 104 +/- 9 mg/dL; homeostasis model assessment index, 3.78 +/- 1.52) in a randomized, placebo-controlled, double-blind, cross-over study. At the end of each treatment phase, oral and intravenous glucose tolerance tests including C-peptide and insulin measurements were performed, and fasting and postprandial lipids were determined. Compared to placebo, telmisartan resulted in a reduction in homeostasis model assessment index (-11%, P = .06) and glucose area under the curve during intravenous glucose tolerance (-11%, P = .04). We observed an increase (+32%, P = .05) in the insulinogenic index indicating an improved beta-cell function. Fasting and postprandial lipid parameters did not change. We observed an increase in adiponectin (6%, P = .09), whereas IL-6, high-sensitivity C-reactive protein, fibrinogen, and free fatty acid concentrations did not change. This indicates that the improvement in glucose metabolism is rather mediated by direct effects, such as activation of PPARgamma. Our data indicate that in insulin-resistant persons 12 weeks of telmisartan result in a significant improvement in glucose metabolism with a predominant improvement in beta-cell function.     

下丘脑垂体疾病对糖脂代谢的影响

糖脂代谢紊乱是代谢综合征的重要组成部分,可增加心脑血管疾病发病风险,导致死亡率升高。下丘脑和垂体是机体内分泌系统的中枢,它们不仅在调节靶器官内分泌功能中发挥重要作用,而且还能通过多种机制维持机体糖脂代谢稳态。下丘脑疾病所致下丘脑结构受损或功能异常,直接造成血糖、血脂代谢失衡,也可能通过影响体内各种激素水平导致糖脂代谢紊...     

Effects of growth hormone on glucose and fat metabolism in human subjects.

This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover and oxidation of free fatty acid (FFA), and experimental evidence suggests a causal link between elevated FFA levels and insulin resistance in skeletal muscle. Observational data in GH-deficient adults do not indicate that GH replacement is associated with significant impairment of glucose tolerance, but it is recommended that overdosing be avoided and glycemic control be monitored.     

Effects of cortisol on carbohydrate, lipid, and protein metabolism: studies of acute cortisol withdrawal in adrenocortical failure

CONTEXT: Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute cortisol deficiency. OBJECTIVE: The objective of the study was to test whether clinical symptoms of weight loss, fatigue, and hypoglycemia could be explained by altered energy expenditure, protein metabolism, and insulin sensitivity during cortisol withdrawal in adrenocortical failure. DESIGN, PARTICIPANTS, AND INTERVENTION: We studied seven women after 24-h cortisol withdrawal and during replacement control during a 3-h basal period and a 3-h glucose clamp. RESULTS: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in basal energy expenditure, increased TSH and T(3) levels, and increased glucose oxidation. Whole-body glucose and phenylalanine turnover were unaltered, but forearm phenylalanine turnover was increased. During the clamp glucose, infusion rates rose by 70%, glucose oxidation rates increased, and endogenous glucose production decreased. Urinary urea excretion decreased by 40% over the 6-h study period. CONCLUSIONS: Cortisol withdrawal increased insulin sensitivity in terms of increased glucose oxidation and decreased endogenous glucose production; this may induce hypoglycemia in adrenocortical failure. Energy expenditure and urea loss decreased, indicating that weight and muscle loss in Addison's disease is caused by other mechanisms, such as decreased appetite. Increased muscle protein breakdown may amplify the loss of muscle protein.     

Effects of peroral and transdermal oestrogen replacement therapy on glucose and insulin metabolism

OBJECTIVE: Conflicting data have been reported previously on the effects of oestrogen replacement therapy on glucose tolerance, and the effects on glycosylated haemoglobin GHbA(1c) have been studied only among diabetics. The objective of this study was to evaluate the effects on glucose and insulin metabolism among nondiabetic women and to compare the outcomes of peroral and transdermal modes of administration. DESIGN: The effects of peroral oestradiol valerate 2 mg/day with placebo gel were compared to those of transdermal 17 beta-oestradiol gel (1 mg oestradiol/day) and placebo tablets in a randomised, double-blind, double-dummy study for six months. PATIENTS: Seventy-nine hysterectomised, nondiabetic postmenopausal women, 39 women in the peroral oestrogen group and 40 in the gel group. MEASUREMENTS: Oral glucose tolerance tests (OGTT) with blood glucose, serum C-peptide and insulin determinations were performed. GHbA(1c), IGF-I and IGFBP-1 were measured at baseline and after six months of therapy. In addition, insulin sensitivity and insulin secretion indices were obtained from OGTT. RESULTS: A small significant reduction in the GHbA(1c) concentration was observed during both peroral (P < 0.05) and transdermal oestrogen therapy (P < 0.05). However, no effect on insulin sensitivity was observed. The response to a standard 75 g oral glucose load was similar in the study groups. Compared with the baseline values, the area under the curve for C-peptide decreased by 8% both in the peroral group (P < 0.05) and in the gel group (P < 0.01). The fasting and postchallenge glucose and insulin levels or insulin release indices were not significantly altered. Peroral oestrogen decreased IGF-I and increased IGFBP-1, but these findings were not associated with the changes in glucose metabolism. CONCLUSIONS: Neither peroral nor transdermal oestradiol replacement therapy seemed to induce any negative effects on glucose metabolism over a time period of 6 months.     

Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH)

Objective To evaluate β‐cell function and insulin sensitivity in subjects with overt (OH) and subclinical hypothyroidism (SH) before and after T4 replacement therapy. Background Disturbances in glucose metabolism have been observed in hypothyroid states. However, the clinical significance and potential reversibility of these alterations by T4 replacement therapy remain to be elucidated especially in patients with SH. Design and patients Parameters of glucose metabolism have been investigated in subjects with OH (n = 12) and SH (n = 11). Insulin sensitivity has been assessed by the euglycaemic–hyperinsulinaemic clamp technique and β‐cell function by mathematical modelling of data derived from an oral glucose tolerance test. Results Fasting and dynamic glycaemia as assessed by the AUC_Glucose remained unaltered following substitution therapy (P > 0·05). Insulin sensitivity significantly improved only in subjects with OH (P < 0·05). Fasting insulin and proinsulin concentrations increased proportionally in both groups (P < 0·05) with the proinsulin : insulin ratio remaining unchanged (P > 0·05). Total insulin secretion was higher in OH before initiation of therapy (P < 0·05). In both groups, dynamic parameters including total insulin secretion, hepatic insulin extraction and the adaptation index were significantly attenuated (P < 0·05) after restoration of thyroid function, whereas the disposition index and the basal insulin secretion rate remained unaltered (P > 0·05). Conclusion In summary, SH and OH are characterized by attenuated basal plasma insulin levels and increased glucose‐induced insulin secretion. T4 replacement therapy partially ameliorates the insulin secretion profile and reduces the demand on pancreatic β‐cells after glucose challenge to an extent that exceeds any effect attributable to the improvement in insulin sensitivity.     

Effects of enteral nutrition preparations on glucose and lipid metabolism in elderly diabetic patients

正Objective To investigate the effects of enteral nutritional emulsions on glucose and lipid metabolism in elderly patients with diabetes.Methods This randomized controlled trail recruited 80 elderly diabetic patients whose MNA-SF scores were between 0-11 with dysphagia or inability for oral feeding and who were randomized into     

Effects of different lipid substrates on glucose metabolism in normal postabsorptive humans.

We investigated the effects on glucose metabolism of the infusion of either long-chain triglycerides (LCT), a mixture of long-chain and medium-chain triglycerides (MCT/LCT), D-beta-hydroxybutyrate (D-beta-OHB), or saline in normal postabsorptive subjects. Plasma insulin, C-peptide, and glucagon concentrations were unchanged in all groups. LCT and MCT/LCT infusions increased levels of plasma free fatty acids (FFA) compared with those of the saline group, whereas D-beta-OHB decreased them. Plasma ketone body concentrations were higher during the D-beta-OHB and triglyceride infusions than during the saline test. Glucose concentrations and appearance (Ra) and disappearance (Rd) rates were not modified during saline infusion. Glucose levels decreased only in the D-beta-OHB and MCT/LCT groups (P < .05), whereas they were unchanged during LCT infusion. Glucose Ra decreased slightly by 15% to 17% in LCT, MCT/LCT, and D-beta-OHB groups (P < .05 v saline). Glucose Rd decreased by 14% to 16% in each lipid-infusion group (P < .05 v saline). Glucose clearance rates decreased by 14% only in the LCT group (P < .001). Glucose oxidation rates did not change significantly during the lipid substrate infusions compared with saline infusion. In conclusion, (1) the effects of fatty acids on glucose metabolism appear to depend on the fatty acid chain length, since only LCT infusion significantly impaired glucose utilization; and (2) in subjects with normal endocrine pancreas function, we found no adverse effects of a short-term increase in lipid substrate availability on glucose production rate and concentration.     

Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance

Recent evidence suggests that increased cortisol secretion, altered cortisol metabolism, and/or increased tissue sensitivity to cortisol may link insulin resistance, hypertension, and obesity. Whether these changes are important in type 2 diabetes mellitus (DM) is unknown. We performed an integrated assessment of glucocorticoid secretion, metabolism, and action in 25 unmedicated lean male patients with hyperglycemia (20 with type 2 diabetes and 5 with impaired glucose intolerance by World Health Organization criteria) and 25 healthy men, carefully matched for body mass index, age, and blood pressure. Data are mean +/- SE. Patients with hyperglycemia (DM) had higher HbA(1c) (6.9 +/- 0.2% vs. 6.0 +/- 0.1%, P < 0.0001) and triglycerides. Cortisol secretion was not different, as judged by 0900 h plasma cortisol and 24 h total urinary cortisol metabolites. However, the proportion of cortisol excreted as 5alpha- and 5beta-reduced metabolites was increased in DM patients. Following an oral dose of cortisone 25 mg, generation of plasma cortisol by hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) was impaired in DM patients (area under the curve, 3617 +/- 281 nM.2 h vs. 4475 +/- 228; P < 0.005). In contrast, in sc gluteal fat biopsies from 17 subjects (5 DM and 12 controls) in vitro 11beta-HSD 1 activity was not different (area under the curve, 128 +/- 56% conversion.30 h DM vs. 119 +/- 21, P = 0.86). Sensitivity to glucocorticoids was increased in DM patients both centrally (0900 h plasma cortisol after overnight 250 micro g oral dexamethasone 172 +/- 16 nM vs. 238 +/- 20 nM, P < 0.01) and peripherally (more intense forearm dermal blanching following overnight topical beclomethasone; 0.56 +/- 0.92 ratio to vehicle vs. 0.82 +/- 0.69, P < 0.05). In summary, in patients with glucose intolerance, cortisol secretion, although normal, is inappropriately high given enhanced central and peripheral sensitivity to glucocorticoids. Normal 11beta-HSD 1 activity in adipose tissue with impaired hepatic conversion of cortisone to cortisol suggests that tissue-specific changes in 11beta-HSD 1 activity in hyperglycemia differ from those in primary obesity but may still be susceptible to pharmacological inhibition of the enzyme to reduce intracellular cortisol concentrations. Thus, altered cortisol action occurs not only in obesity and hypertension but also in glucose intolerance, and could therefore contribute to the link between these multiple cardiovascular risk factors.     

小檗碱与糖脂代谢

小檗碱是从黄连中提取的生物碱,是一种传统中草药.除已知的抗感染作用外,近来还发现它与肝细胞低密度脂蛋白受体mRNA稳定性、AMP活化蛋白激酶(AMPK)活性、葡萄糖转运蛋白4(GLUT4)易位、代谢综合征相关基因表达等有关,从而对糖脂代谢的调节起重要作用.另外,小檗碱可改善肝功能,降低颈动脉粥样硬化血管内膜厚度.     

Study on the effect of insulin on carbohydrate and lipid metabolism in obese subjects with normal glucose tolerance]

In altogether 32 test persons with normal weight and obese test persons glucose-insulin-tolerance-tests were carried out. In obese persons with normal carbohydrate tolerance -- characterized by 50 g oral glucose tolerance test -- by the decreased glucose assimilation coefficients and the significantly increased level of glycaemia after intravenous application of glucose a disturbance of the glucose-insulin-homoeostasis is already implied. Basal and glucose-stimulated concentrations of IRI in the peripheral venous blood were significantly increased in obese persons. The parameters of lipolysis glycerol and free fatty acids show after a glucose-stimulated insulin excretion and after exogenic insulin application a somewhat retarded decrease in obese persons compared with the control group. In connection with the significantly increased insulin levels in obese persons these findings might refer to a decreased antilipolytic effect of insulin. The two fundamental physiological effects of insulin in the carbohydrate and fat metabolism -- glucose utilization and inhibition of lipolysis -- seem to be distrubed in the same way in obesity.     

Effects of gastric inhibitory polypeptide on glucose and lipid metabolism of isolated rat adipocytes

The effects of gastric inhibitory polypeptide (GIP) on glucose and lipid metabolism of isolated rat adipocytes were investigated. In a dose-dependent manner, GIP stimulated 2-deoxy-glucose uptake increasing the glucose transport rate by up to 140% at a concentration of 10(-7) mol/l. GIP also stimulated the conversion of 14C-glucose into extractable lipids by up to 81% at 10(-7) mol/l. Insulin-stimulated 2-deoxy-glucose uptake and lipogenesis were additively enhanced by the presence of GIP. Insulin binding was slightly but not significantly increased by addition of GIP, mainly due to an increase in receptor affinity. GIP had a weak lipolytic activity, but lipolysis elicited by glucagon or isoproterenol was potently reduced. In conclusion, independent of its insulinotropic action, GIP showed a insulin-like activity on glucose metabolism and lipolysis in rat adipose tissue. The possible role of GIP for the development of obesity is discussed.     

桑枝生物碱对糖脂代谢的作用

桑枝提取物是以桑树枝为原材料,经提取、分离、纯化得到的有效提取物,主要包含生物碱、黄酮、多糖和氨基酸等成分。其中,降糖有效部位即桑枝总生物碱(SZ-A)具有双糖酶抑制活性,由1-脱氧野尻霉素(1-DNJ)、荞麦碱(FAG)和1,4双脱氧-1,4-亚氨基-D-阿拉伯糖醇(DAB)组成,DNJ占70%,FAG和DAB各占15%。口服SZ-A后,DNJ、FAG和DAB分别在0.67、1.30和0.67 h内达到最大血浆浓度。SZ-A对小肠糖苷酶有高选择性的抑制作用,单药使用有效降低HbA1c 1.0%,在用药早期即可降低1 hPG,胃肠道副作用比阿卡波糖减少50%。此外SZ-A还具有调节糖脂代谢和肠道菌群、保护胰岛β细胞、改善葡萄糖刺激的胰岛素分泌功能、刺激GLP-1分泌等作用,适用于T2DM餐后高血糖患者,特别是T2DM新诊断患者、有社交需求的患者、伴脂代谢异常患者、偏好天然药物的患者、使用糖苷酶抑制剂胃肠副作用明显的患者。今后期待更多的临床试验,以进一步验证其有效性、与其他药物的相互作用、药物不良反应、降糖以外的疗效等,为临床应用提供更多的循证证据。