Changes in glucagon kinetics and processing in patients with acute pancreatitis

BACKGROUND/AIMS: The kinetics of the pancreatic hormone glucagon in patients with acute pancreatitis have not been investigated as carefully as those of insulin, in spite of its crucial influence on energy metabolism. In the present study, we studied the kinetics of glucagon and glucagon-related peptides assessed by radioimmunoassay. Furthermore, the molecular forms of these peptides were examined using gel filtration chromatography, and the glucagon processes in the pancreas and intestine in the early stage in patients with acute pancreatitis were investigated. METHODOLOGY: Fourteen patients with acute pancreatitis were enrolled in this study. Eight had severe pancreatitis (group S) and six had mild pancreatitis (group M). Ten healthy volunteers were also enrolled as the normal control (group C). Serum levels of glucagon and glucagon-related peptides were assessed on the second admission day in groups S and M, and in an early morning fasting state in group C, using glucagon non-specific N-terminal (glucagon-like immunoreactivity: GLI) and specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The molecular forms of these peptides were also estimated using gel filtration chromatography. We then discuss the glucagon processes based on these findings. RESULTS: Serum GLI and IRG in groups S and M were significantly higher than those of group C (P < 0.01), while those in group S were also significantly higher than those in group M (P < 0.05). In all patients in groups S and M, except for only three in group S, a peculiar glicentin-like peptide (GLLP: MW about 8000) other than pancreatic glucagon was observed in IRG gel filtration chromatography, which was clearly absent from group C. CONCLUSIONS: The kinetics and processing of glucagon in patients with acute pancreatitis were quite different from those of healthy subjects. In patients with acute pancreatitis, the peculiar processing of glucagon proceeded in the intestine quite differently from ordinary glucagon processing either in the pancreas or in the intestine, generating a peculiar GLLP.     

2型糖尿病患者胰高血糖素及生长抑素功能变化分析

目的检测2型糖尿病患者（T2DM组）及健康人（NC组）的胰岛素（INS）、C肽（C-P）、胰高血糖素（GLC）、生长抑素（SS）的水平,探讨2型糖尿病患者胰岛功能受损可能的机制。方法 T2DM组40例和NC组19名均行口服75g葡萄糖耐量试验（OGTT）,于0、30、120min采静脉血,分别测定空腹及口服葡萄糖后30、120min血糖及INS、C-P、GLC、SS。结果 （1）与NC组比较,T2DM组INS、C-P明显降低（P〈0.01）;（2）T2DM组各时间点GLC较NC组显著升高（P〈0.01）。（3）T2DM组口服葡萄糖后30min、120min的SS水平均较0min显著升高,30min较NC组低（P〈0.05）,120min较NC组高（P〈0.01）。结论 T2DM患者INS、C-P分泌水平较正常人显著下降;GLC分泌亢进;SS分泌紊乱。     

Peculiar glucagon processing in the intestine is the genesis of the paradoxical rise of serum pancreatic glucagon in patients after total pancreatectomy

BACKGROUND/AIMS: Although glucagon has been detected even in the serum of totally pancreatectomized patients and the origin was suggested to be the intestine, the kinetics of glucagon are not well known after pancreatectomy. In the present study, we investigated the kinetics of glucagon and glucagon-related peptides in pancreatectomy patients and discuss the glucagon processes. METHODOLOGY: Ten patients who had undergone total pancreatoduodenectomy reconstruction using Billroth II type procedures (group PX) and 12 normal subjects (group C) were also enrolled in this study. All patients received a 75-g oral glucose tolerance test in the early morning fasting state. Serum glucagon levels were assessed using the glucagon specific C-terminal (immunoreactive glucagon: IRG) and nonspecific N-terminal (glucagon-like immunoreactivity: GLI) radioimmunoassays. The molecular forms of these glucagon-related peptides were also estimated using the gel filtration chromatography method before and after the oral glucose load. RESULTS: After the glucose load, serum GLIs were increased significantly in group PX suggesting that these were affected by the alimentary tract reconstructions. Serum IRGs were significantly increased in group PX, but decreased in group C after oral glucose load suggesting that these paradoxical increased responses in group PX might be associated with the insulin secretion deficiencies, but not associated with the alimentary tract reconstruction. CONCLUSIONS: The paradoxical rise in IRGs based on the findings of gel filtration chromatography in group PX were possibly due to the generated peculiar glicentin-like peptide from the glucagon precursor, preproglucagon, after total pancreatectomy, which might be processed in intestines in association with the insulin deficiencies.     

The peculiar processing of glucagon and glucagon-related peptides in patients after pancreatectomy

BACKGROUND/AIMS: Although, glucagon has been detected even in the serum of totally pancreatectomized patients and the origin was suggested to be the intestine, the kinetics of glucagon is not well known after pancreatectomy. In this study, we investigated the kinetics of glucagon and glucagon-related peptides and discuss the glucagon processes in the pancreas and intestine in pancreatectomy patients. METHODOLOGY: Seven patients who had undergone pancreatoduodenectomy reconstruction using Child's procedures (distal pancreatojejunostomy, choledochojejunostomy and gastrojejunostomy) (group PD) and five patients who had undergone distal pancreatectomy (group DP) served as the subjects of this study. In addition to these two groups, five patients who had undergone gastrectomy reconstructions using the Billroth II procedure (group GX), to examine whether the alimentary tract reconstructions themselves would have any effect on the kinetics of glucagon, and 10 normal subjects (group C) were also enrolled in this study. All patients received a 75-g oral glucose tolerance test in the early morning fasting state. Serum glucagon levels were assessed using the glucagon non-specific N-terminal (glucagon-like immunoreactivity: GLI) and specific C-terminal (immunoreactive glucagon: IRG) radioimmunoassays. The molecular forms of these glucagon-related peptides were also estimated using the gel filtration chromatography method before and after the 75-g oral glucose load. RESULTS: After the glucose load, serum GLIs were increased significantly in groups GX and PD suggesting that these were affected by the alimentary tract reconstructions. Serum IRGs including true pancreatic glucagon were slightly increased in groups PD and DP after oral glucose load suggesting that these paradoxical responses might be associated with the glucose tolerance deficiencies observed in both groups, but not associated with the alimentary tract reconstruction. CONCLUSIONS: The paradoxical rise of IRGs based on the findings of gel filtration chromatography were possibly due to the generated peculiar glicentin-like peptide and pancreatic glucagon from the glucagon precursor, preproglucagon, after pancreatectomy, which is processed in association with the glucose tolerance deficiencies after pancreatectomy.     

Effects of immune neutralization of corticotropin-releasing hormone, adrenocorticotropin, and beta-endorphin in the surgically stressed rat

Specific in vivo neutralization was used in an attempt to explore the roles of corticotropin-releasing hormone (CRH), ACTH, and beta-endorphin during surgical stress in Sprague-Dawley rats. Rats were randomly assigned to groups (n = 20-30/group) that received iv injections of rabbit antirat/human CRH (anti-r/hCRH), antihuman ACTH (anti-hACTH), antihuman beta-endorphin (anti-h beta-endorphin), or normal rabbit serum. Three hours later all animals were subjected to a uniform stress consisting of ether anesthesia, surgical laparotomy, and phlebotomy of 7 ml via the inferior vena cava. Survival rates were recorded, and RIAs were performed for ACTH, beta-endorphin, and corticosterone. Rats treated with anti-h beta-endorphin had a survival rate of 64%, which was significantly higher than that of the control group (33%; P less than 0.025, by analysis of variance). Anti-r/hCRH or anti-hACTH treatment was not associated with a change in survival rate. Plasma immunoreactive beta-endorphin levels were markedly decreased in the group treated with anti-h beta-endorphin (P less than 0.0001). Anti-r/hCRH had no effect on plasma immunoreactive ACTH or beta-endorphin. Plasma immunoreactive ACTH and corticosterone levels were decreased in the group treated with anti-hACTH (P less than 0.0001 and P less than 0.01, respectively). We conclude that 1) beta-endorphin immune neutralization is associated with a survival advantage during severe surgical stress, suggesting that circulating beta-endorphin might have deleterious effects during stress; 2) In severe stress, acute immune neutralization of CRH is not sufficient to inhibit ACTH, beta-endorphin, and corticosterone secretion, suggesting significant involvement of other secretagogues of the pituitary-adrenal axis; and 3) moderate decreases in corticosterone cannot affect survival, presumably because glucocorticoids play only a permissive role in maintaining cardiovascular stability during surgical stress.     

Changes in the impedance cardiogram occurring with change in posture in patients with heart disease

The response of the heart to changes in posture from supine through sitting to standing was recorded by impedance cardiography. The study comprised 22 normal subjects and 74 patients with a variety of heart diseases. The results demonstrate that in normal subjects acceleration of blood in systole decreased on sitting and standing. In subjects with impaired cardiac function this acceleration increased on sitting and standing from the supine position. This clear-cut difference in response provides a subtle method of detecting impaired function and in addition, provides a method of monitoring the effects of vasodilator or other treatment.     

肝硬化患者血浆内皮素和胰高血糖素水平的变化及其临床意义

目的 研究肝硬化时血浆内皮素-1(ET-1)和胰高血糖素(GLU)水平的改变及其与肝功能损害和门脉高压形成的关系。方法 采用放射免疫分析法测定40例肝硬化患者和18例对照组空腹血浆ET-1和GLU水平。用彩色多普勒超声测定门静脉及脾静脉的直径、流速和流量。结果 肝硬化患者血浆ET-1和GLU水平显著高于对照组。按肝功能Child-Pugh分级将肝硬化患者分为A、B、C三组，各组血浆ET-1和GLU水平依次升高。合并腹水的肝硬化患者血浆ET-1和GLU水平显著高于未合并腹水者。血浆ET-1和GLU水平与门静脉和脾静脉的直径以及脾静脉的流量呈显著正相关。结论 肝硬化患者血浆ET-1及GIU水平升高反映了肝功能损害的严重程度，同时在门静脉高压的形成和发展过程中起着重要的作用。     

Changes in joint laxity occurring during pregnancy.

We have studied changes in peripheral joint laxity occurring during pregnancy in 68 females using both the finger hyperextensometer to quantify laxity at the metacarpophalangeal joint of the index finger and Beighton et al.'s modification of the Carter and Wilkinson scoring system. Although the latter system recorded no change, the more sensitive hyperextensometer demonstrated a significant increase in joint laxity during the last trimester of pregnancy (0.02 greater than p greater than 0.01) over the readings from the same individuals after parturition. When primigravidae and multigravidae were compared, a highly significant increase in laxity was found in women having their second baby over those having their first (0.01 greater than p greater than 0.001), though no further increase in laxity occurred in subsequent pregnancies.     

Forms of malnutrition in stressed and unstressed patients

PCM can be usefully considered in terms of edematous (kwashiorkor-like) and nonedematous (marasmic) forms, as long as the limitations of the traditional terms are kept in mind. The body composition of subjects with undernutrition, or total starvation, both appear to maintain an extracellular fluid volume at a normal level, which increases as a percentage of the shrinking body weight. This is in contrast to patients with hospital malnutrition, in whom there is often an absolute increase in the extracellular volume while the body cell mass is shrinking. Data from the starvation literature suggest that the adult subject must gain approximately 10% of his or her body weight as extracellular expansion before edema is clinically evident. Preliminary evidence indicates that the hospitalized patient with the edematous form of malnutrition is at greater risk for complications and death when undergoing an operation, or requiring intensive care. The depleted patient who shows a rise in a depressed serum albumin after 7 to 10 days of TPN will have an improved prognosis when undergoing the stress of an elective operation. This improvement appears to be more the result of decreasing the expanded extracellular fluid volume than achieving a major increase in protein stores. The severely catabolic patient, particularly during episodes of major infection, can be expected to benefit by a nutritional intake that is carefully designed to provide calorie and nitrogen equilibrium. Nutritional intake high enough to guarantee positive balances of calories and nitrogen should be delayed until the acute catabolic stimulus has subsided, at which time the nutritional objective is to rebuild lost tissue.     

2型糖尿病患者口服糖耐量试验胰升糖素和生长抑素水平的变化

检测60例2型糖尿病患者和34名正常对照者空腹及口服75 g葡萄糖2h后胰升糖素、生长抑素(SS)和C肽水平。结果显示,与对照组比较,糖尿病组空腹胰升糖素、SS及糖负荷后2 h SS明显降低（均P＜0.01）,空腹及2 h C肽明显升高（均P＜0.01）。两组糖负荷后2 h激素水平均显著高于空腹(均P＜0.01),与对照组比较,糖尿病组胰升糖素（1.40±0.48对1.20±0.30,P＜0.05）和SS(2.79±2.17对1.14±0.22,P＜0.01)餐后增加倍数更高,C肽增加倍数较低（3.58±3.10对8.33±6.99,P＜0.01）;两组空腹胰升糖素水平与SS呈正相关（均P＜0.01）。以上结果提示,2型糖尿病患者不仅β细胞功能紊乱,尚存在α、δ细胞相关激素紊乱。     

胰高血糖素在冠心病心力衰竭患者血浆中水平的变化和临床意义(英文)

目的:探讨冠心病所致心力衰竭患者血浆中胰高血糖素水平的变化及其临床意义。方法:选择冠心病所致心力衰竭患者30例作为心力衰竭组,年龄性别与之相匹配的门诊健康体检者30例作为正常对照组。对心力衰竭病人按中国慢性心力衰竭诊治指南给予强心、利尿、扩血管等综合治疗7～10 d,观察其治疗前后胰岛血糖素水平的变化。结果:治疗前,心力衰竭组血浆胰高血糖素水平明显高于正常对照组[(205.67±120.22)ng/L比(90.53±20.5)ng/L,P<0.05]。治疗后,心力衰竭组血浆胰高血糖素水平为(120.42±30.33)ng/L,较治疗前明显下降(P<0.05)。结论:心力衰竭患者血浆胰高血糖素水平明显升高,症状控制后又逐渐降低至接近正常水平,或许胰高血糖素可以作为临床判断冠心病心力衰竭患者病情变化的指标之一。     

Naturally occurring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes.

Treatment of erythrocytes with the thiol-specific oxidant azodicarboxylic acid bis(dimethylamide) (diamide) enhances their phagocytosis by adherent monocytes. Phagocytosis of diamide-treated erythrocytes required that the cells were opsonized with whole serum, since complement inactivation abolished phagocytosis. Opsonization with whole serum containing 20-100 times the physiological concentration of naturally occurring anti-band-3 antibodies enhanced phagocytosis of diamide-treated erythrocytes. High inputs of anti-band-3 also restored phagocytosis of erythrocytes that had been incubated with complement-inactivated serum. Elevated concentrations of anti-spectrin antibodies were ineffective in whole and complement-inactivated serum. Specific recognition of diamide-treated erythrocytes by anti-band-3 antibodies may be due to generation of anti-band-3 reactive protein oligomers on intact diamide-treated erythrocytes. Generation of such oligomers was dose-dependent with respect to diamide. Bound anti-band-3 alone was not sufficient to mediate phagocytosis. It resulted in deposition of complement component C3b on the cells through activation of the alternative complement pathway in amounts exceeding that of bound antibodies by two orders of magnitude. Thus, anti-band-3 and complement together mediate phagocytosis of oxidatively stressed erythrocytes, which stimulate senescent erythrocytes with respect to bound antibody and complement.     

Changes in the glucagon and growth hormone levels in the blood plasma of healthy persons and of patients with disordered glucose tolerance after insulin administration

In 15 patients with the normal body mass and disturbed glucose tolerance a glycemia level was higher and insulin levels lower than in 10 healthy persons in the first 20 min after i. v. insulin injection (1.2 units per 1 m2 of the body surface). It was suggestive of resistance to insulin in such patients. The level of glucagon in the blood plasma after insulin injection rose in the patients as well as in healthy persons indicating an unchanged response of pancreatic alpha-cells to insulin in this type of diabetes mellitus. A growth hormone level in the blood after insulin injection bid not significantly change in both groups. Glucose homeostasis after insulin injection was regulated not by the growth hormone but mainly by glucagon.     

Changes in ventricular depolarization and repolarization in 116 cases of surgically treated interauricular communication

The postoperative changes of ventricular depolarization and repolarization were studied in 116 cases of atrial septal defect 3 to 8 years after surgical treatment. High fidelity multiple unipolar registries as well as the vectorcardiographic curves in three planes were obtained. Before surgery there were 101 RBBB (87.07% of this series). Of 22 minor degree RBBB, 17 (77.27%) showed no changes, 2 (9.09%) became distal blocks and 3 (13.64%) became intermediate degree RBBB. Of 77 preoperative intermediate degree RBBB, 20 (25.97%) diminished to a minor degree, 1 (1.3%) became a distal block and 2 (2.6%) augmented to an advanced degree. Fifteen distal right blocks (12.93% of the total of cases) persisted postoperatively. Signs of right ventricular enlargement disappeared in all the cases. The right Q-Tc, previously prolonged in 38 cases (32.76% of this series), was normal after surgery. Peaked or negative interpolated T waves disappeared in right precordial and transitional leads. The electrocardiographic features of ventricular repolarization seem to reflect hemodynamic improvement better than those of depolarization. The electrocardiogram permits classification of the disturbances of right ventricular conduction, while the vectorcardiogram shows variations in dimensions of the right ventricle.     

Radiation injuries of the intestines

The outstanding early symptom of radiation injury of the intestine is diarrhea, mild to severe in degree. Later manifestations are pain, demonstrable ulceration and stricture formation with partial or complete obstruction. The early lesions, located usually on the anterior wall of the rectum and rectosigmoid, are characterized by an edematous friable mucous membrane. Later ulceration, with a grayish white slough, occurs at the level of the cervix. In time perirectal fibrosis resembling a “frozen” pelvis may develop and result in obstruction. In the severe injuries with stenosis, hemorrhage or persistent severe pain, temporary or permanent colostomy may be required with or without resection of the bowel. Intractable pain may be treated by colostomy and resection of the afferent nerve supply to the rectum. The ideal therapy is, of course, prophylactic, the avoidance of radiation injury. Whether or not it is possible by attention to the details of technic to administer effective carcinocidal doses of irradiation without occasional severe injury to adjacent normal tissue such as the rectum seems questionable at present.