Radioimmunoassay of gastric inhibitory polypeptide

A radioimmunoassay for the measurement of gastric inhibitory polypeptide (GIP) in unextracted plasma in man has been developed using a rabbit antiserum raised against porcine GIP. Porcine GIP was employed also as standard and to produce a 125I-labelled tracer. The assay was able to distinguish 110 pg/ml GIP from zero in plasma samples. Negligible cross-reactivity was demonstrated with cholecystokinin, insulin, pancreatic polypeptide, glucagon, secretin, and vasoactive intestinal polypeptide. The mean overnight fasting plasma GIP level in 28 normal subjects was 203 pg/ml (range: undetectable--420 pg/ml). Plasma GIP levels rose, within 45 minutes of eating a mixed meal, to a mean level of 1573 pg/ml.     

Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs.

To determine whether gastric inhibitory polypeptide (GIP) promotes the clearance of chylomicron triglycerides (TG) from the circulation in dogs, chyle collected from donor dogs via a thoracic duct fistula was infused at a rate of 2 ml/min i.v. into normal recipient dogs during an infusion of either porcine GIP (1 microgram/kg per h) or saline as a control. In the GIP-infused dogs the rise in plasma TG was significantly below that of the control animals [mean peak of 36 +/- 4 mg/dl vs. 82 +/- 18 mg/dl (P less than 0.05)]. It is concluded that GIP exerts an effect upon the removal of chylomicron TG from the blood. The results suggest that GIP may play a physiologic role in the disposition of ingested fat.     

Lack of direct splanchnic nerve inhibitory effects on histamine-induced gastric acid secretion in rats

Effects of stimulation of the splanchnic nerves (gastric sympathetic nerves) on the histamine-induced increases in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized rats. The gastric acid secretion and MBF were increased by i.v. infusion of a submaximal dose of histamine (50 micrograms/kg/min). Stimulation of the splanchnic nerve, carried out under an increased steady state of acid secretion and MBF, inhibited the histamine-induced acid secretion and MBF and these effects were abolished by phentolamine and augmented by propranolol. The manner of inhibition by splanchnic nerve stimulation was similar to the inhibitory effects of vasopressin on histamine-induced acid secretion and MBF, but differed from the inhibitory effects of somatostatin; i.v. infusion of vasopressin reduced both histamine-induced acid secretion and MBF, whereas i.v. infusion of somatostatin reduced the histamine-induced acid secretion more effectively than MBF. Inhibitory effects of splanchnic nerve stimulation or infusion of vasopressin on the histamine-induced gastric acid secretion and MBF paralleled the increases in the systemic blood pressure during such treatment. These results suggest that the splanchnic nerves have no direct inhibitory effect on the histamine-induced gastric acid secretion in rats. Decreases in the histamine-induced gastric acid secretion are probably secondary to the decrease in the MBF during splanchnic nerve stimulation.     

Effects of atropine and gastric inhibitory polypeptide on hepatic glucose uptake and insulin extraction in conscious dogs.

Previous studies comparing the effects of oral, intraportal, and peripheral venous administration of glucose in conscious dogs demonstrated a significant increase in hepatic extraction of insulin only after oral glucose, but similar hepatic uptake of glucose after oral and intraportal glucose, which was greater than that after peripheral intravenous glucose infusion. This study evaluated the effect of atropine blockade of the parasympathetic nervous system on the increased fractional hepatic extraction of insulin and the role of gastric inhibitory polypeptide (GIP) on augmented hepatic uptake of oral glucose in conscious dogs with chronically implanted Doppler flow probes on the portal vein and hepatic artery, and catheters in the portal and hepatic veins and carotid artery. Since atropine infusion decreased absorption of glucose, and in order to achieve comparable portal vein levels of glucose and insulin, the dogs receiving atropine were given 1.9 +/- 0.1 g/kg glucose, compared with the control dogs who received 1.1 +/- 0.1 g/kg. The percentage of the glucose load that was absorbed was greater in the dogs not given atropine (80 +/- 4 vs. 44 +/- 7%), but because of the different loads, the absolute amount of glucose absorbed was similar in both groups (20.2 +/- 1.6 vs. 21.7 +/- 4.1 g). Although delayed by atropine, the peak portal vein glucose and insulin concentrations and the amounts presented to the liver were similar in both groups. However, the increased portal vein plasma flow and fractional hepatic extraction of insulin observed after oral glucose was not observed in the dogs infused with atropine. The net hepatic glucose uptake after oral glucose was significantly less at 10, 20, and 45 min in the atropine-treated dogs, and the area under the curve over the 180-min period was 44% less. However, the latter was not statistically significant. Infusion of GIP with peripheral intravenous glucose did not increase hepatic uptake of glucose or the fractional hepatic extraction of insulin compared with peripheral intravenous glucose alone. These results indicate an important role for parasympathetic innervation in the augmented fractional hepatic extraction of insulin, and increased portal vein plasma flow after oral glucose. Although a relationship between the augmented fractional extraction of insulin and the net hepatic glucose uptake may exist, it does not necessarily indicate that the former is required for the latter. Such parasympathetic innervation may be involved in the greater removal of glucose by the liver after oral compared with peripheral glucose administration. The augmented hepatic uptake of glucose and fractional hepatic extraction of insulin after oral glucose doesn not appear to be mediated by gastric inhibitory polypeptide.     

Impaired feedback control of fat induced gastric inhibitory polypeptide (GIP) secretion by insulin in obesity and glucose intolerance

Abstract. To investigate the role of endogenous insulin on the secretion of immunoreactive gastric inhibitory polypeptide (IR-GIP) the response of IR-GIP and immunoreactive insulin (IRI) to an oral fat load (100 g triglyceride) alone and during an intravenous glucose infusion (0.7 g/kg/h) was examined in normal weight and obese subjects. In normal weight subjects the fat induced integrated rise of IR-GIP was 112.7 ± 9.4 ng/ml/120 min. When glucose and fat were given together this IR-GIP response was lowered to 46.2 ± 2.9 ng/ml/120 min while the serum IRI response to i.v. glucose and the glucose tolerance were enhanced by fat ingestion. In obese subjects with normal glucose tolerance the GIP suppressing effect of i.v. glucose infusion was less marked than in controls. The integrated IR-GIP response to fat ingestion was 225.6 ± 20.3 ng/ml/120 min and to fat plus glucose 152.6 ± 14.8 ng/ml/120 min. In obese subjects with glucose intolerance i.v. glucose completely failed to lower the exaggerated secretion of IR-GIP following oral fat. Thus, a graded abnormality of the GIP response to glucose induced insulin release occurs in obesity with normal and pathological glucose tolerance. After reducing the ideal body weight of six obese subjects with glucose intolerance by hypocaloric diet for 3 weeks the exaggerated rise of IR-GIP after oral fat was reversed and the lowering effect of i.v. glucose on the IR-GIP response re-established.     

Glucose-induced responses of insulin and gastric inhibitory polypeptide in various animal models

In order to clarify the role of gastric inhibitory polypeptide (GIP) in an enteroinsular axis, 19 healthy mongrel dogs were divided into following groups: 5 normal dogs (N), 4 dogs with gastrojejunostomy (GJ), 5 dogs with duodenal fistula (D) and 5 vagotomized dogs (V). Four weeks after the operation glucose was administered orally or intraduodenally in a conscious state. In group D, glucose administration was repeated under atropine injection (A). Glucose-induced response of plasma GIP was exaggerated in all the groups compared with group N. The regression equation reported by Lauritsen and Moody was obtained in each dog from the ratio of plasma insulin to blood glucose and from plasma GIP. The slope of the regression line was elevated in group GJ and reduced in group V. However, groups D and A did not reveal any difference in the slope of the regression line compared with group N. From the present study, it might be concluded that the B-values in Lauritsen and Moody's equation indicates the sensitivity of the B cell in the pancreatic islet and that GIP secretion plays an important role in the glucose-induced insulin response even in the conditions with various surgical modifications.     

Interrelationships among insulin, glucagon, and gastric inhibitory polypeptide in insulinoma

The interrelationships of serum insulin, glucagon, and gastric inhibitory polypeptide were examined in 13 patients with insulinoma during fed and fasted states. Compared with normal subjects, patients with insulinoma had significantly lower glucose and higher insulin levels during both the fed and the fasted states. Although glucagon concentration was higher at the completion of the fast in patients with insulinoma compared with normals, no significant differences were apparent during the fed state. No difference was noted in gastric inhibitory polypeptide either during the fed state or at the termination of the fast. Under the conditions of the study, no direct suppressive effect of insulin on glucagon or gastric inhibitory polypeptide secretion was apparent. In addition, as opposed to that in normals, the insulinotropic effect of glucagon did not appear to be blunted by hypoglycemia in most of the patients. After glucagon injection, all symptomatically hypoglycemic patients experienced an amelioration of symptoms and restoration of the plasma glucose into the normal range.     

The role of adrenaline and of the vagus in gastrin release and acid secretion in dogs

Serum gastrin, gastric acid secretion and plasma adrenaline in response to intravenous injection of 2-deoxy-D-glucose and to insulin were measured in six dogs with gastric fistulae before and after denervation of the antrum and the intestine (antral-intestinal vagotomy). Serum gastrin and gastric acid secretion were also measured in the same dogs during intravenous infusion of adrenaline in doses which produced an elevation of plasma adrenaline to levels occurring during hypoglycaemia and after the injection of 2-deoxy-D-glucose. Antral-intestinal vagotomy reduced basal gastrin concentration slightly and basal gastric acid secretion considerably. The rise in serum gastrin in response to 2-deoxy-D-glucose and hypoglycaemia was abolished while the increase in gastric acid secretion was reduced after antral-intestinal vagotomy. Beef meal-stimulated gastrin secretion was the same before and after vagotomy. Intravenous infusion of adrenaline had no effect on either serum gastrin or gastric acid secretion. It is concluded that in the dog, in contradistinction to man, gastrin release after insulin is dependent on an intact vagus. Release of gastrin by adrenaline in the dog does not appear to be physiological since it is not achieved by the amount of adrenaline released in response to hypoglycaemia.     

解痉多肽在应激胃黏膜适应性保护中的作用

目的 研究解痉多肽(spasmolytic polypeptide,SP)在水浸束缚应激(WRS)大鼠胃黏膜的基因表达变化,探讨其在应激胃黏膜适应性保护中的作用.方法 采用单次和重复水浸束缚应激制作模型,动态监测胃黏膜血流量(GMBF),大体及光镜下观察黏膜损伤程度(UI)及组织学变化,逆转录-多聚酶链反应(RT-PCR)检测研究SP基因表达变化,免疫组化染色进一步证实SP表达.结果 ①单次应激造成胃黏膜广泛损伤,但损伤指数在3、5、7 d逐渐减小,至7 d降为208%,GMBF逐渐恢复,至7 d上升为正常94.5%,SP基因表达逐渐增强(0.50±0.12 vs 0.71±010,P＜0.01),免疫组化染色计分为0.94±0.10 vs 1.50±0.13 (P＜0.01);②重复应激后胃黏膜产生适应性,胃黏膜血流量上升,损伤逐渐减轻,4次应激后,损伤指数降低为单次应激的22%,胃黏膜血流量上升为正常94.2%,并且胃腺区细胞增殖,SP基因表达增强(0.57±0.01 vs 0.97±003,P＜0.01),免疫组织化学染色计分为1.25±0.11 vs 2.56±0.16(P＜0.01).结论 SP可能参与了应激胃黏膜适应性细胞保护.     

Role of endogenous prostaglandins in gastric secretion and mucosal defense

Prostaglandins are found in high concentration in the gastric mucosa and gastric juice. Exogenous prostaglandins inhibit acid secretion, stimulate mucus and bicarbonate secretion, alter mucosal blood flow, and provide dramatic protection against a wide variety of agents which cause acute mucosal damage. The physiological role of prostaglandins is still being elucidated. There is now strong evidence that endogenous prostaglandins modulate acid secretion by blocking the histamine-stimulated increase in cyclic AMP within the parietal cell. This function is probably controlled by intraluminal pH. It is likely that mucus and bicarbonate secretion by both stomach and duodenum are influenced by endogenous prostaglandins. A physiological role of prostaglandins in mucosal protection is less certain. Prostaglandins are released by trivial injury, and this probably serves a defensive function. A mucosa which is prostaglandin-depleted is more susceptible to damage, but does not spontaneously ulcerate. It is conceivable that peptic ulcer disease may be in part caused by an impaired mucosal prostaglandin response to food.