CO2气腹前后糖尿病兔血糖的变化及机制

目的探讨二氧化碳气腹对糖尿病兔在气腹前后血糖变化的影响及其机制。方法利用四氧嘧啶制作糖尿病兔模型,建立不同压力气腹,观察术前、术后0、2、6、12h各时间点血糖、胰岛素、C肽浓度的变化。结果气腹结束后,血糖、胰岛素、C肽浓度上升,至气腹后12h,10mmHg气腹组血糖、胰岛素、C肽浓度较气腹前无明显差异,15mmHg气腹组血糖、胰岛素较气腹前高。10mmHg和15mmHg气腹组之间,血糖、胰岛素变化无明显差异(P>0.05),C肽浓度变化有明显差异(P<0.05)。结论CO2气腹对糖尿病兔的血糖有明显的影响,且影响程度与气腹压力相关,其机制与气腹引起的应激反应和胰腺损害有关。     

Effects of insulin on food intake and plasma glucose level in fat-fed diabetic rats

Schedules of insulin treatment which reliably increased eating in fat-fed diabetic rats were studied for their effect on plasma glucose concentrations. An inverse correlation between intake and plasma glucose was observed in fat-fed diabetics given long-term treatment with protamine-zinc insulin (PZI); however changes in glucose did not account for the differential effect of insulin on food intakes in normal controls or normal and diabetic rats fed a low-fat food. A single injection of 1 U PZI which increased eating in fat-fed diabetics but not normal controls 17–23 hr later did not reduce glucose concentrations from hyperglycemic levels in diabetics during the same time period. Injections of regular insulin increased eating in fat-fed diabetic and normal rats in a comparable fashion, but did not reduce plasma glucose in diabetics as low as in normal animals. The results show that the effect of exogenously administered insulin on food intake in fat-fed diabetics is largely unrelated to changes in circulating glucose levels and suggest that metabolic consequences of insulin treatment other than hypoglycemia may underlie the effect of the hormone on feeding in these animals.     

Interleukin-6 and oxidative stress in plasma of alloxan-induced diabetic rabbits after pioglitazone treatment

There is evidence that oxidative stress might be implicated in promoting a state of systemic inflammation in diabetic patients. Understanding the role of reactive oxygen species in the inflammatory response in diabetes becomes essential in finding preventive treatments. Pioglitazone is a new oral antidiabetic agent with potent antioxidant and anti-inflammatory properties. The drug is a high affinity ligand of peroxisome proliferator-activated receptor gamma. This receptor seems to be involved in the control of inflammation by modulating the production of inflammatory mediators. In the present study, the changes in some markers of enhanced oxidative stress and in the level of pro-inflammatory interleukin-6 (IL-6) were examined in plasma of diabetic rabbits after 4 and 8 weeks of pioglitazone treatment. Ascorbic acid (AA) concentration and total antioxidant status (TAS) in plasma of diabetic animals were diminished and significantly elevated after pioglitazone treatment (p < 0.05). Protein carbonyl groups (PCG) content and IL-6 concentration were elevated in plasma of diabetic animals and significantly diminished after pioglitazone treatment. The results obtained in the present study confirm the relations of cytokine systems with oxidative stress in plasma of diabetic subjects. They also suggest the antioxidative and antinflammatory properties of pioglitazone.     

The effect of cherry sticks extract on the levels of glycoproteins in alloxan-induced experimental diabetic mice

This study was designed to evaluate the effect of ethanolic cherry sticks extract on the levels of glycoproteins in alloxan-induced diabetic mice. Forty-five adult male albino mice were divided equally into three groups: Group 1: control, Group 2: diabetic mice, Group 3: diabetic mice treated with cherry sticks extract as well as to eighteen mice treated with cherry sticks extract only for toxicity test. All treatments were administered via an intragastric tube. Diabetes was induced in the mice of Group 3 by an intraperitoneal injection with 100 mg/kg body weight of alloxan. Oral administration of cherry sticks extract at a concentration of 250 mg/kg body weight for 15 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as those of hexose, hexosamine, fucose, and sialic acid in the diabetic mice treated with the cherry sticks extract as compared to untreated diabetic mice, with no adverse effects in mice treated only with cherry sticks extract. In conclusion, cherry sticks extract proved to have a beneficial effect on the diabetic mice in this study. In light of these advantageous results, it is advisable to broaden the scale of use of cherry sticks extract in a trial to alleviate the adverse effects of diabetes.     

Increased platelet, but unaltered fibrinogen, accumulation in experimental thrombi in alloxan-induced diabetic rabbits.

Platelets from diabetic humans and animals have been found previously to be hypersensitive to agonists, including thrombin, in vitro but it is unclear if this hypersensitivity also occurs in vivo and leads to a greater thrombotic tendency. In the present study, the effect of diabetes was examined on thrombus formation and vessel wall responses which result from continuous intimal injury induced by indwelling aortic catheters in rabbits. Platelet and fibrin(ogen) associated with the thrombus and damaged aortae were examined. Control or alloxan-induced diabetic rabbits (9-12 months after initial treatment) were injected with 51Cr-labeled autologous platelets and 125I-labeled fibrinogen (prepared from control rabbits) before insertion of indwelling aortic catheters. The anesthetized rabbits were perfused-fixed after 20 hr or 4 days. The dry weight of thrombus that formed was determined and platelet and fibrin(ogen) accumulation in thrombi and on injured aortae were calculated from the associated 51Cr and 125I, respectively. In diabetic rabbits, more platelets accumulated in the thrombi which formed after either 20 hr or 4 days, although the weight of thrombus and net fibrin(ogen) incorporation into the thrombus were not different from corresponding control rabbits. Net platelet and fibrin(ogen) association with the injured aortae were not different between control and diabetic rabbits. It is likely that the increased platelet accumulation in arterial thrombi in diabetic rabbits which results from continuous injury to aortae is a consequence of hypersensitivity of these platelets to thrombin generated in the thrombus and at the sites of vessel injury.     

Influence of peripheral and intracerebroventricular glucose and insulin infusions on peripheral and cerebrospinal fluid glucose and insulin levels

There is much evidence that glucose and insulin are related to the regulation of food intake and the maintenance of peripheral glucose homeostasis through actions of the central nervous system. However, evidence concerning the penetration of peripheral glucose and insulin into the cerebrospinal fluid (CSF) and the relationship between both peripheral and CSF glucose and insulin levels is still missing. In the reported experiments it is shown that insulin is present in the CSF (17 +/- 3.6 microU/ml CSF versus 44 +/- 6.0 microU/ml plasma) but that CSF insulin does not follow rises of peripheral insulin to 136 microU/ml plasma during 4.5 hours. On the other hand CSF glucose (55 +/- 3.1 mg/dl CSF) follows rises of peripheral glucose levels with a delay of about 30 min. Increase of CSF glucose by infusing glucose into the third brain ventricle elicits a prolonged decrease in peripheral glucose levels. Infusion into the third ventricle of insulin only does not change peripheral glucose. However, infusion of a combination of insulin and glucose in the third ventricle leads to a gradual increase in peripheral glucose and elicits a disappearance of the decrease in peripheral glucose after glucose only infusion into the CSF. During third ventricle infusion experiments no change in peripheral insulin could be observed. It will be argued that changes in CSF glucose and insulin contribute to maintenance of peripheral glucose homeostasis.     

Expression of visfatin in alloxan-induced diabetic rat testis

Diabetes mellitus is a potential epidemic all over the world and causes dysfunction of reproductive activity. Visfatin, one of the adipokines, is present in various tissues including the testis. Our hypothesis was the level of testicular visfatin is affected in diabetic condition. The aim of the present study was to investigate the expression and localization of visfatin in the diabetic rat testis. No similar studies have been performed in diabetic rat testis with reference to visfatin. Overnight fasted adult male Wistar rats were made diabetic by the administration of alloxan (150 mg/kg i.p., in 0.9% saline). Blood glucose levels were tested on five days after alloxan treatment, rats with high blood glucose levels (>250 mg/dL) were considered as diabetic. Immunolocalization and Western blotting analysis of visfatin were performed. Correlation of visfatin expression was made in relation to body weight, testis weight, glucose concentration and serum testosterone level. Expression of visfatin was observed in Leydig cells, spermatocytes and sperm in control as well as in the diabetic group. Mild immunostaining of visfatin was observed in affected seminiferous tubules of alloxan-induced diabetic rat testis. Western blot analysis showed decreased expression of testicular visfatin in diabetic rats. The expression of visfatin showed a positive correlation with serum testosterone levels, body and testis weight, while a negative correlation was observed with blood glucose levels. This study showed involvement of visfatin in diabetic associated impairment of testicular activity.     

Histopathological abnormalities of prolonged alloxan-induced diabetes mellitus in rabbits

The objective of this study was to investigate the prolonged complications of untreated diabetes on histomorphology of rabbits. Diabetes mellitus was experimentally induced in one group of New Zealand white male rabbits by intraperitoneal administration of four doses of alloxan @ 80 mg/kg b.w. at weekly intervals following 12 h fasting. Other group of rabbits served as healthy controls that received isotonic saline in a similar manner. The establishment of diabetes mellitus was confirmed by fasting blood glucose levels. For histomorphological study of different organs, 50% of the animals were killed after 7 weeks and the rest after 26 weeks. Routine haematoxylin and eosin stain and Gomori's modified stain were used. The blood glucose level of diabetic rabbits increased significantly throughout the experimental period. The peak values for blood sugar were on the sixth week of the study. Further, histomorphological alterations were recorded in pancreas, kidneys, lungs, heart and brain in diabetic rabbits. However, mild changes were observed in gastrointestinal tract with proliferation of yeasts in the stomach. With the progress of untreated diabetes, the histoanatomical alterations intensify and extend to almost all organs of the body and appear to increase the susceptibility of gastric mucosa to yeast cell proliferation.     

Fasting glucose/insulin index and insulin levels 2-h after glucose load are predictors of the development of type 2 diabetes

To determine whether fasting glucose/insulin (FG/I) ratio and insulin levels 2 h after 75-g oral load of glucose (IL-2 h PG) are predictors for type 2 diabetes mellitus, a comparative 2 year follow-up study was conducted. Ninety-six healthy subjects 30 years of age or older, randomly selected from the general population of Durango, Mexico were included in two groups: 1) risk group: members had both baseline FG/I ratio and IL 2-h PG within the lower and upper quartile, respectively, and 2) control group, whose members had baseline FG/I ratio and IL 2-h PG within the second and third quartiles, respectively. Multivariate logistic regression was used to compute the relative risk for the development of type 2 diabetes. The family history of diabetes (RR 10.1; IC95% 2.7-15.8, p < 0.01), glucose intolerance (RR 9.8; IC95% 1.7-13.4, p < 0.01), abdominal obesity (RR 6.1; IC95% 1.5-10.1, p < 0.01), and the low FG/I ratio and high IL 2-h PG (RR 3.3; IC95% 1.4-8.2, p < 0.05) were strong predictors for type 2 diabetes. Critical values for predicting criteria of FG/I ratio and IL 2-h PG were of 4.0 y 180 microUI/ml, respectively. In conclusion, the measurement of FG/I ratio and IL 2-h PG is an accurate indicator for estimating the risk of developing type 2 diabetes.     

Comparative effects of oral administration of Citrullus colocynthis and insulin injection on serum biochemical parameters of alloxan-induced diabetic dogs

Citrullus colocynthis seeds are traditionally used as antidiabetic medication in Mediterranean countries. An experiment was designed to evaluate the comparative effects of oral administration of C. colocynthis and insulin injection on the serum biochemical parameters of diabetic dogs. Twelve apparently healthy mixed breed dogs were selected and randomly allocated into three groups, two diabetic groups and one control group (n?=?4). Diabetes was induced with alloxan tetrahydrate. One diabetic group and the control group were treated with a dose of 100?mg/kg/day of C. colocynthis. Three days after confirmation of diabetes mellitus, the dogs were orally administered C. colocynthis capsules twice daily for 8?days. The other diabetic group was injected with a combination of neutral protamine Hagedorn (NPH) [insulin isophane (NPH)–Human-Exir] and regular crystalline insulin [insulin (regular)–Human-Exir] (70% NPH and 30% regular) twice daily for 8?days. Blood samples were collected from the cephalic vein at three time points: immediately before alloxan injection, 3?days after diabetic induction, and 12?h after the last treatment. Serum concentrations of glucose, insulin, triglyceride, cholesterol, high-density lipoprotein, low-density lipoprotein, blood urea nitrogen, creatinine, alkaline phosphatase, alanine aminotransferase, and aspartic aminotransferase were measured. Results showed that the serum concentrations of glucose in insulin-injected dogs were not significantly different with those of the C. colocynthis-administered diabetic dogs. The serum concentrations of all measured parameters showed no significant change 8?days after the administration of C. colocynthis in the control group, whereas oral administration (capsule) of C. colocynthis at a dose of 100?mg/kg/day caused severe and mild diarrhoea in the control and C. colocynthis-treated diabetic groups, respectively. The present study indicated a significant antihyperglycaemic effect of C. colocynthis fruit and supports its traditional usage in the treatment of diabetes mellitus.     

Separation of physiological factors influencing glucose insulin kinetics in diabetic patients

A new quantitative method was developed for separation of physiological factors influencing glucose intolerance in diabetes mellitus using a three-compartmental model and the intravenous glucose tolerance test (IVGTT) in humans. The present model includes the physiologic factors of the hepatic glucose balance function, the peripheral tissue's glucose utilization rate, and the insulin secretion rate. The insulin sensitivity parameter and hepatic glucose sensitivity parameter were estimated in optimal fitting of the model-based data of glucose and insulin concentrations to the measured IVGTT data in 9 normal and 11 diabetic subjects. The results show that these sensitivity parameters are important for separation of the effects of the interactive physiologic factors, and, also useful in evaluating different glucose-insulin kinetics in 3 clinical groups of normal and diabetic subjects.     

Effects of leg exercise on insulin absorption in diabetic patients

To examine the effects of leg exercise on insulin absorption from various injection sites, 125I-labelled rapid actin insulin (9 units) was injected subcutaneously into the leg, arm or abdomen of patients with insulin-dependent diabetes before one hour of intermittent leg (bicycle) exercise and on a resting, control day. Insulin disappearance from the leg increased by 135 per cent during the first 10 minutes of leg exercise (P less than 0.05) and remained 50 per cent above resting levels after 60 minutes (P less than 0.02). Leg exercise had no effect on insulin disappearance from the arm, but insulin disappearance from the abdomen was reduced during the post-exercise recovery period (P less than 0.02). As compared to leg injection, arm or abdominal injection reduced the hypoglycemic effect of exercise by 57 per cent (P less than 0.02) and 89 per cent (P less than 0.005), respectively. Leg exercise accelerates insulin absorption from the leg. Arm or abdominal injection avoids this acceleration during leg exercise and reduces exercise-induced hypoglycemia.     

Effects of dietary-fiber levels on RANK/RANKL/OPG expression in the appendix of weanling rabbits

Background/purposeThe dietary fiber can regulate the intestinal mucosal immunity, and the M cell is the portal for initiating mucosal immunity. We investigated the effects of dietary fiber on the transport of Escherichia coli to assess the function of microfold (M) cells in the appendix.MethodA total of 150 New Zealand rabbits were fed three diets (high fiber (HF): 31.72%; control: 37.36%; low dietary fiber (LF): 41.84%; neutral detergent fiber (NDF). An infection model was established in vivo using E. coli containing green fluorescent protein as the indicator in appendix loops. Samples were collected before and after inoculation with indicator for 10, 30, or 60 min. The M cells number, differentiation-related genes and proteins were monitored by respectively using immunofluorescence, Q-PCR and Western-blot.ResultsThe number of M cells in HF group was significantly higher than that of LF group before and at 10 min, 30 min post injection with E.coli (P < 0.01), which has an opposite at 60 min. The number of fluorescent E. coli transported across the appendix was significantly increased in the HF group (P < 0.01) compared with the LF group at 30 min (P < 0.001); expression of RANKL gene and protein levels were no difference between HF and LF group. The variation tendency of RANK, OPG genes and proteins were consistent with the change of M cell transport indicator number in different time points.ConclusionOur study showed that a high-fiber diet can increase number of M cells and speed up antigen transfer under regulation of ANKL/OPG/RANK system.     

局部应用胰岛素对糖尿病大鼠烫伤创面愈合的影响

目的研究局部应用胰岛素对糖尿病大鼠烫伤创面愈合的作用,初步探索相关机制。方法 60只Wistar大鼠经高脂饮食喂养和小剂量脲佐菌素（STZ）多次注射诱导糖尿病,5周后,造成背部皮肤20%TBSA深Ⅱ度烫伤。随机分为胰岛素治疗组和对照组（每组30只大鼠）,分别于创面下浸润注射0.2 U中性胰岛素和等体积0.9%氯化钠溶液。观察创面愈合速度及伤后第1、4和12天两组创面表皮角质形成细胞迁移、炎症细胞浸润以及胶原沉积情况。酶联免疫吸附测定法检测创面活化素A（Activin A）、单核细胞趋化蛋白-1（MCP-1）和血小板衍生因子A（PDGF-A）水平。结果胰岛素治疗组创面愈合时间明显缩短,血糖无明显变化。和对照组相比,胰岛素治疗组伤后第4天创面表皮迁移舌长度明显延长;伤后第12天创面胶原沉积增加;创面巨噬细胞浸润和消退的时间提前,巨噬细胞在创面表达特征与创面MCP-1表达趋势一致。伤后第1、4天胰岛素治疗组创面Activin A的表达分别（142.52±15.26）pg/mL和（271.46±49.73）pg/mL,较对照组创面的（52.36±33.18）pg/mL和（46.08±8.92）pg/mL明显增加（P=0.0057,0.0001）,PDGF-A于伤后第1、4天的表达分别为（52.12±9.00）pg/mL和（74.75±7.00）pg/mL较对照组的（47.35±8.21）pg/mL和（34.07±5.05）pg/mL也有明显增加（P=0.4080,0.0001）。结论局部应用胰岛素促进创面巨噬细胞的浸润和提早消退、促进表皮细胞的迁移和血管生成相关细胞因子表达和胶原组织沉积,从而促进糖尿病大鼠烫伤创面的愈合。