High plasma cholecystokinin response following ingestion of test meal by patients with non-insulin dependent diabetes mellitus

Postprandial responses of plasma cholecystokinin (CCK) in patients with non-insulin dependent diabetes mellitus (NIDDM) were studied with a CCK specific radioimmunoassay. After the ingestion of a liquid test meal, plasma CCK levels increased from the basal level of 9.8 +/- 1.1 pg/ml to a peak of 19.4 +/- 1.8 pg/ml at 20 min in healthy subjects (n = 10). The ingestion of a test meal in patients with NIDDM (n = 10) resulted in a significantly greater increase of plasma CCK than in healthy subjects and a significant increase of plasma CCK from a basal level of 14.2 +/- 4.4 pg/ml to a peak of 47.4 +/- 12.4 pg/ml at 10 min.     

Hypersomatostatinemia in chronic renal failure

Plasma concentrations of somatostatin-like immunoreactivity (SLI) were determined in uremic patients on maintenance hemodialysis. Plasma SLI levels were significantly (p less than 0.001) elevated in 26 diabetic uremic patients (67.1 +/- 6.8 pg/ml, mean +/- SE) and in 24 non-diabetic uremic patients (43.5 +/- 7.2 pg/ml), when compared with 60 healthy subjects (5.0 +/- 0.7 pg/ml). Paired pooled plasma from uremic patients before and after hemodialysis was subjected to a reverse-phase octadecasilyl-silica (C-18) cartridge and then the extract was gel filtered on a Sephadex G-25 column (1.6 X 90 cm). Both elution profiles showed two peaks of SLI which coeluted with synthetic somatostatin (SS)-28 and SS-14 markers, respectively. The SS-28-like immunoreactivity (LI) peak, which was estimated by using SS-14 as a reference standard, was 3-fold larger than that for SS-14 LI. On the basis of immunoequivalency of the two components in the present assay, SS-28 LI constitutes approximately 75% of circulating somatostatin. In conclusion, plasma SLI is substantially high in uremic patients of both diabetic and non-diabetic etiology and the SS-28 is a predominant form of circulating SLI in these patients, probably, in part, for a lower clearance of this molecule.     

Plasma somatostatin and vasoactive intestinal polypeptide responses to an oral mixed test meal in obese patients

Ten obese and 10 control subjects were studied in basal conditions and after ingestion of a standard mixed test meal. Blood glucose, insulin, somatostatin (SLI) and vasoactive intestinal polypeptide (VIP) concentrations were determined before and 30, 60, 90, 120, 180 and 240 min after the start of the meal. Basal SLI levels in the obese (14.4 +/- 0.7 ng/l) were not significantly different from those in the controls (15.5 +/- 0.8 ng/l), whereas after the meal a blunted secretory response was recorded. Baseline plasma VIP levels were higher in the obese (29.7 +/- 1.5 ng/l) than in the control subjects (19.8 +/- 1.3 ng/l) and, similarly to the controls, were unaffected by meal ingestion. Data suggest that in the course of obesity an enhanced VIP secretion in association with a diminished SLI responsiveness to meals occurs.     

Changes in somatostatin-like immunoreactivity in lungs from perinatal guinea pigs and the effects of somatostatin-14 on lung liquid production.

Somatostatin-like immunoreactivity was measured by radioimmunoassay with a monoclonal antibody in lungs from perinatal guinea pigs (62 +/- 2 days of gestation). Fetuses delivered by Caesarean section and dissected before breathing showed 4748 +/- 758 pg/lung (n = 25). Fetuses allowed to breathe (neonates) showed marked increases in activity: 7629 +/- 1355 pg/lung (n = 12) after breathing 30 seconds, and 10729 +/- 1064 pg/lung (n = 6) after breathing 3 minutes (2.3-fold increase, P < 0.005). Values then declined (5203 +/- 1050 pg/lung (n = 9) at 30 minutes; 1458 +/- 105 pg/lung (n = 4) at 60 minutes). Changes were similar in pg/g wet tissue. HPLC characterized the immunoreactive peptides as somatostatin-14 (SS-14) and somatostatin-28 (SS-28) in both fetuses and neonates (n = 11). SS-28 made up only 13.7 +/- 1.7% of the activity; this percentage did not change with breathing. The effects of synthetic SS-14 on lung liquid production were investigated in in vitro lungs from 42 fetal guinea pigs. All 21 preparations immersed in 10(-5)-10(-7) M SS-14 during the middle hour of 3 h incubations reduced production, often approaching zero after treatment (rates, ml/kg body weight per h, succeeding hours: 10(-5) M (n = 9), 3.09 +/- 0.68, 0.93 +/- 0.39, -0.05 +/- 0.60 (fall significant during and after treatment, P < 0.025-0.005); 10(-6) M (n = 6), 3.06 +/- 0.68, 1.29 +/- 0.58, 0.36 +/- 0.38 (P < 0.05-0.005); 10(-7) M (n = 6), 1.96 +/- 0.66, 1.11 +/- 0.34, 0.64 +/- 0.28 (P < 0.05-0.025).(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary platelet-activating factor excretion is elevated in non-insulin dependent diabetes mellitus.

Proteinuria is currently considered a very sensitive predictor of diabetic nephropathy, but 20-25% of all diabetic patients with negative Albustix reaction excrete higher than normal (< 20 mg/24 h) amounts of albumin in their urine. It is our hypothesis that platelet-activating factor (PAF), a potent glycerophospholipid that acts as a chemical mediator for a wide spectrum of biological activities, including increased vascular permeability, may be produced in significant amounts during periods preceding microalbuminuria. In this study, we compared urinary PAF excretion in Mexican-American subjects who were diagnosed with non-insulin dependent diabetes mellitus (NIDDM) with their healthy control counterparts. The age of the NIDDM subjects (45.9 +/- 2.1 years) was not significantly different from the healthy control group, which was 39.4 +/- 2.7 years (P < 0.0672). The NIDDM subjects (body mass index, 29.9 +/- 1.1 compared to 26.1 +/- 0.9 kg/m2 in healthy controls) were characterized by significantly increased (P < 0.05) fasting plasma glucose (192 +/- 11 vs. 97 +/- 4 mg/dl in healthy controls), fasting insulin (20.9 +/- 2.4 vs. 12.3 +/- 1.6 microU/ml), fasting C-peptide (2.93 +/- 1.26 vs. 1.48 +/- 0.51 ng/ml), and hemoglobin A1c (10.3 +/- 0.7 vs. 5.6 +/- 0.3%), respectively. The urine output for the NIDDM and control subjects were 1942 +/- 191 ml/24 h and 1032 +/- 94 ml/24 h, respectively, and urinary albumin excretion (UAE) rates were estimated to be 38 +/- 7 micrograms/min and 11 +/- 1 micrograms/min, respectively. The NIDDM subjects produced significantly increased levels of urinary PAF (2606.3 +/- 513.1 ng/24 h compared with 77.9 +/- 14.1 ng/24 h in controls (or 1706.3 +/- 420.8 ng/ml compared with 85.4 +/- 17.8 pg/ml of urine, in NIDDM and control subjects, respectively). We found that urinary PAF excretion was significantly correlated with microalbumin excretion (r = 0.7) especially at UAE rates greater than 30 mg/day and more importantly, some NIDDM patients with negative Albustix reaction (i.e. normal UAE) produced significantly more PAF, suggesting that PAF excretion may precede microalbuminuria and that subtle injury to the kidneys are present in NIDDM long before overt albuminuria ensues, urinary PAF measurements could potentially therefore serve as a sensitive indicator of renal injury in diabetes mellitus. These results lend further credence to our hypothesis that PAF may be the biochemical compound linking the various members of the insulin resistance syndrome.     

Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes

Maximal dynamic exercise results in a postexercise hyperglycemia in healthy young subjects. We investigated the influence of maximal exercise on glucoregulation in non-insulin-dependent diabetic subjects (NIDDM). Seven NIDDM and seven healthy control males bicycled 7 min at 60% of their maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. In both groups, glucose production (Ra) increased more with exercise than did glucose uptake (Rd) and, accordingly, plasma glucose increased. However, in NIDDM subjects the increase in Ra was hastened and Rd inhibited compared with controls, so the increase in glucose occurred earlier and was greater [147 +/- 21 to 169 +/- 19 (30 min postexercise) vs. 90 +/- 4 to 100 +/- 5 (SE) mg/dl (10 min postexercise), P less than 0.05]. Glucose levels remained elevated for greater than 60 min postexercise in both groups. Glucose clearance increased during exercise but decreased postexercise to or below (NIDDM, P less than 0.05) basal levels, despite increased insulin levels (P less than 0.05). Plasma epinephrine and glucagon responses to exercise were higher in NIDDM than in control subjects (P less than 0.05). By use of the insulin clamp technique at 40 microU.m-2.min-1 of insulin with plasma glucose maintained at basal levels, glucose disposal in NIDDM subjects, but not in controls, was enhanced 24 h after exercise. It is concluded that, because of exaggerated counter-regulatory hormonal responses, maximal dynamic exercise results in a 60-min period of postexercise hyperglycemia and hyperinsulinemia in NIDDM. However, this event is followed by a period of increased insulin effect on Rd that is present 24 h after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumor necrosis factor alpha production as a possible predictor of relapse in patients with multiple sclerosis.

No biological parameter is currently available as a specific marker of multiple sclerosis (MS) activity. The aim of this study was to determine whether an evolution of the neurological disability is associated with a modified profile of cytokine production. Clinical disease activity was quantitated by the Kurtzke's expanded disability status scale (EDSS). Whole blood was stimulated with phytohemagglutinin (PHA) for 2 hours at 37 degrees C and the activated plasma was assayed for Tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1 beta). Relapsing-remitting MS patients enduring a relapse (RRMS, in relapse) (721 +/- 58 pg/ml, n = 27) and chronic progressive MS (CPMS) patients (516 +/- 33 pg/ml, n = 17) had an higher TNF-alpha production capacity as compared to healthy subjects (143 +/- 25 pg/ml, n = 17), RRMS, stable patients, (123 +/- 11 pg/ml, n = 26) or other neurological diseases (OND) without immunological or inflammatory disease in the peripheral immune compartment (131 +/- 24 pg/ml, n = 14) (t test: p < 0.0001). IL-1 beta production was also significantly higher but to a lesser extent in the same conditions. Concentration of TNF-alpha was also found to be significantly higher in the cerebrospinal fluid (CSF) of CPMS patients (199 +/- 7.8 pg/ml, n = 7, p < 0.0001) but also in RRMS, in relapse (149 +/- 5.7 pg/ml, n = 11, p < 0.05) as compared to RRMS, stable (130 +/- 4.4 pg/ml, n = 7) or OND without inflammatory or immunological disease of the central nervous system (CNS) (142 +/- 6.2 pg/ml, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal (n = 12) and chemically sympathectomized (n = 11) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the early postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.     

Age-related change in plasma concentration of 7B2 (a novel pituitary polypeptide) in normal humans

Using a specific radioimmunoassay, we measured concentrations of plasma 7B2 (a novel pituitary polypeptide) immunoreactivity (7B2-IR) in normal human subjects, patients with chronic renal failure and those with liver cirrhosis. Mean (+/- SEM) values of plasma 7B2-IR in normal healthy men and women were 55.8 +/- 1.2 pg/ml (n = 266) and 56.1 +/- 0.9 pg/ml (n = 408), respectively. The elevation of plasma 7B2-IR showed a relationship with age of the subjects, in both men (r = 0.39, t = 6.86, p less than 0.001) and women (r = 0.35, t = 7.44, p less than 0.001). Plasma 7B2-IR concentrations were elevated in patients with chronic renal failure (536 +/- 45 pg/ml, Mean +/- SEM, n = 10) as well as those in liver cirrhosis (95 +/- 10 pg/ml, Mean +/- SEM, n = 15) compared to values in normal subjects, suggesting that 7B2 is mainly eliminated through the kidney and is partly metabolized in the liver.     

Comparison of somatostatin-28 and somatostatin-14 clearance by the perfused rat liver

The hepatic clearances of somatostatin (SS)-28 and SS-14 by the perfused rat liver were compared, using a recirculating, plasma-free, erythrocyte-containing perfusion system. The disappearance rate constant, half time, clearance, and hepatic extraction ratio when 1.2 nM SS-28 was added to the perfusate were 0.0221 +/- 0.0051 min-1, 36.6 +/- 7.6 min, 0.34 +/- 0.08 mL/min, and 17.2 +/- 3.9%, respectively. The corresponding values obtained when SS-14 was added to the perfusate were 0.0405 +/- 0.0022 min-1, 17.3 +/- 1.0 min, 0.71 +/- 0.05 mL/min, and 35.4 +/- 2.6%, respectively. The differences between the SS-28 and SS-14 indices were all statistically significant. In addition, the perfusates with SS-28 added were eluted on Sephadex G-25 fine columns and somatostatinlike immunoreactivity (SLI) was determined. No SS-14 was found in perfusate containing SS-28 at both 5 and 30 min after the beginning of the perfusion. To investigate whether or not the liver plays an important role in the clearance of SS-28 or the conversion of SS-14 in vivo, the plasma disappearance of 2 micrograms SS-28 was compared in the whole rat and the functionally hepatectomized model. The half time of plasma SS-28 was 1.43 +/- 0.12 min in the whole rat, significantly shorter than the 2.20 +/- 0.14 min in the hepatectomized model. Gel filtration of plasma extract samples at 0.5 min after the SS-28 injection showed two major peaks of SLI: a first peak corresponding to SS-28 and a second peak coeluted in the position of SS-14 in both the whole rat and the hepatectomized model. At 4 min after the SS-28 injection, the first peak disappeared and only a small second peak was observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nutrient ingestion on glucagon-like peptide 1 (7-36 amide) secretion in human type 1 and type 2 diabetes.

Exogenous glucagon-like peptide 1(GLP-1) bioactivity is preserved in type 2 diabetic patients, resulting the peptide administration in a near-normalization of plasma glucose mainly through its insulinotropic effect. GLP-1 also reduces meal-related insulin requirement in type 1 diabetic patients, suggesting an impairment of the entero-insular axis in both diabetic conditions. To investigate this metabolic dysfunction, we evaluated endogenous GLP-1 concentrations, both at fasting and in response to nutrient ingestion, in 16 type 1 diabetic patients (age = 40.5 +/- 14yr, HbA1C = 7.8 +/- 1.5%), 14 type 2 diabetics (age = 56.5 +/- 13yr, HbA1C = 8.1 +/- 1.8%), and 10 matched controls. In postabsorptive state, a mixed breakfast (230 KCal) was administered to all subjects and blood samples were collected for plasma glucose, insulin, C-peptide and GLP-1 determination during the following 3 hours. In normal subjects, the test meal induced a significant increase of GLP-1 (30', 60': p < 0.01), returning the peptide values towards basal concentrations. In type 2 diabetic patients, fasting plasma GLP-1 was similar to controls (102.1 +/- 1.9 vs. 97.3 +/- 4.01 pg/ml), but nutrient ingestion failed to increase plasma peptide levels, which even decreased during the test (p < 0.01). Similarly, no increase in postprandial GLP-1 occurred in type 1 diabetics, in spite of maintained basal peptide secretion (106.5 +/- 1.5 pg/ml). With respect to controls, the test meal induced in both diabetic groups a significant increase in plasma glucagon levels at 60' (p < 0.01). In conclusion, either in condition of insulin resistance or insulin deficiency chronic hyperglycemia, which is a common feature of both metabolic disorders, could induce a progressive desensitization of intestinal L-cells with consequent peptide failure response to specific stimulation.     

Plasma concentrations of endothelin in patients with abnormal vascular reactivity. Effects of ergometric exercise and acute saline loading

We measured circulating concentrations of endothelin, a recently discovered vasoconstrictor peptide produced by vascular endothelial cells, in healthy subjects and in patients with abnormal vascular reactivity. Endothelin concentrations were determined by radio-immunoassay after extraction of plasma using Sep-Pak C-18 cartridges in healthy subjects (n = 20), in patients with diabetes mellitus type I (n = 10), in patients with mild to moderate essential hypertension (n = 12) and in non-dialyzed patients with stable chronic renal failure (n = 12). Plasma concentrations were similar in healthy controls, in diabetics and in hypertensive patients averaging 5.0 +/- 0.6 pg/ml, 4.7 +/- 0.2 pg/ml and 6.5 +/- 1.0 pg/ml, respectively. In contrast, plasma concentrations of endothelin were markedly elevated in patients with chronic renal failure averaging 16.6 +/- 2.9 pg/ml (p less than 0.005). No correlations were observed between serum creatinine concentrations ranging from 124 to 850 mumol/l or blood pressure and plasma concentrations of endothelin. Bicycle ergometric exercise in six healthy subjects and an acute modest i.v. saline load of 1,000 ml of 0.45% NaCl administered within 60 min in six patients with mild essential hypertension did not affect plasma concentrations of endothelin. Thus, it is unlikely that vascular synthesis of endothelin is related to acute physiological changes in systemic hemodynamics or to the circulatory and renal responses to acute extracellular fluid volume (ECFV) expansion. A potential role of endothelin, however, in the control of regional blood flow cannot be excluded. Elevated plasma concentrations of endothelin observed in patients with chronic renal failure require further investigations.     

Beta-endorphin and insulin/glucose responses to different meals in obesity.

The responses of plasma beta-endorphin, insulin and glucose to two different isocaloric mixed meals--high carbohydrate (CHO meal) and high fat (fat meal)--were assessed in women with android obesity before (n = 11) as well as after (n = 5) weight reduction, and in normal-weight controls (n = 8). Basal plasma beta-endorphin concentrations in the obese subjects (7.7 +/- 1.2 pmol/l) were significantly (p less than 0.005) higher than in the controls (3.8 +/- 0.5 pmol/l) and were not influenced by weight loss. Fasting plasma levels and the integrated releases of insulin and glucose, both after the CHO meal and after the fat meal were significantly higher in the obese subjects than in the controls. The fat meal induced no changes in beta-endorphin levels in either group. After the CHO meal a significant decrease in plasma beta-endorphin concentration was observed only in the obese group before weight reduction. An influence on beta-endorphin release by macronutrients is hypothesized.     

Chlorpropamide-ethanol induced met-enkephalin secretion in dogs: release mechanisms and biochemical characterisation

Circulating met-enkephalin-like immunoreactivity (MLI) rises in man after chlorpropamide and ethanol although the origin and molecular forms of circulating MLI are not well defined. We have studied the response to oral ethanol in conscious and anaesthetised dogs pretreated with chlorpropamide. In conscious dogs MLI rose from a basal level of 29 +/- 7 pg/ml to a peak of 55 +/- 14 pg/ml 10 min after ethanol (P less than 0.001). In anaesthetised animals, following ethanol, plasma MLI rose in caval (35 +/- 6 pg/ml to a peak of 70 +/- 10 pg/ml), in portal (28 +/- 6 pg/ml to 51 +/- 6 pg/ml) and in adrenal blood (897 +/- 316 pg/ml to 1483 +/- 298 pg/ml; P less than 0.001). Biogel P-4 chromatography of caval and portal basal plasma showed 87% of MLI measured coeluted with the synthetic pentapeptide, while chromatography of peak plasma showed that only 65% coeluted with the pentapeptide and the remaining 35% was of larger molecular size. Sephadex G75 chromatography of adrenal vein plasma revealed three peaks of MLI of differing molecular sizes (8 k = 69.7%; 3-5 k = 12.1% and the pentapeptide = 18.2%). Treatment of the column fractions with trypsin and carboxypeptidase B resulted in the generation of new MLI with peaks of approximate molecular sizes 31 k (10.4%), and 18 k (37.1%) in addition to 8 k (40.0%), 3-5 k (5.0%) and the pentapeptide (7.5%). Acetaldehyde involvement in MLI release was investigated. Following acetaldehyde infusion, plasma MLI rose both in caval (35 +/- 9 pg/ml to 86 +/- 8 pg/ml) and adrenal vein (417 +/- 121 pg/ml to 1768 +/- 433 pg/ml) bloods. Thus we have established an animal model which enables further study of the mechanisms of MLI release and characterisation of the molecular forms. The adrenal medulla, unlike the gut, may be an important source of circulating met-enkephalin and acetaldehyde formation an essential intrinsic component of chlorpropamide-ethanol induced met-enkephalin release.     

Effect of different anesthetics on immunoreactive atrial natriuretic factor concentrations in rat plasma

The effect of different conditions of blood withdrawal and use of different anesthetics on immunoreactive atrial natriuretic factor (IR-ANF) concentrations in plasma was studied in rats. The concentration of IR-ANF in plasma from jugular vein of non-anesthetized conscious rats, cannulated either 24 hr before blood withdrawal was 93.9 +/- 17.1 pg/ml (n = 30); and 48 hr: 81.9 +/- 11.5 pg/ml (n = 29). Immobilization stress (4 hr) increased IR-ANF concentration: 248.0 +/- 80.2 pg/ml (n = 5). Anesthesia by morphine, diethyl-ether, chloral hydrate and ketamine chlorhydrate increased IR-ANF concentrations to 2,443.0 +/- 281.2 pg/ml (n = 24), 806.1 +/- 74.6 pg/ml (n = 64), 224.0 +/- 81.4 pg/ml (n = 20), and 195.0 +/- 20.3 pg/ml (n = 51), respectively. IR-ANF in plasma of sodium-pentobarbital and urethane anesthetized rats was 59.2 +/- 6.7 pg/ml (n = 10) and 42.6 +/- 8.1 pg/ml (n = 8), respectively. These changes in IR-ANF evoked by different types of anesthetics and different conditions of blood withdrawal have to be taken into consideration during studies on the physiopathological role of atrial natriuretic factor.     

Human atrial natriuretic polypeptide in plasma of patients with anorexia nervosa

To examine the effects of chronic dehydration and starvation on plasma levels of human atrial natriuretic polypeptide (hANP) in human subjects, the basal level and saline-induced rise of plasma hANP in 7 patients with anorexia nervosa were compared with those in age-matched healthy subjects. The unstimulated level of plasma hANP was markedly high in the patients with anorexia nervosa (patients vs. control; 55.4 +/- 9.0 pg/ml vs. 11.4 +/- 6.1 pg/ml, P less than 0.01). However, no significant increase of plasma hANP in the anorectic patients was observed in response to saline-infusion, while a 3-fold increase over the basal level of plasma hANP was noted in the saline-infused normal young subjects. These results show that hANP may be secreted to an inadequate extent, hence the release would be resistant to volume-loading. The pathophysiological meaning of such a high plasma concentrations of hANP in anorexia nervosa is the subject of ongoing studies.     

Galanin and pancreastatin inhibit stimulated insulin secretion in the mouse: comparison of effects

The effects of the two intrapancreatic peptides galanin and pancreastatin on basal and stimulated insulin and glucagon secretion in the mouse were compared. It was found that at 2 min after intravenous injection of galanin or pancreastatin (4.0 nmol/kg), basal plasma glucagon and glucose levels were slightly elevated. Galanin was more potent than pancreastatin to elevate basal plasma glucagon levels: they increased from 60 +/- 15 to 145 +/- 19 pg/ml (p less than 0.01) after galanin compared to from 35 +/- 5 to 55 +/- 8 pg/ml (p less than 0.05) after pancreastatin. Plasma insulin levels were lowered by galanin (p less than 0.05), but not by pancreastatin. CCK-8 (6.3 nmol/kg) or terbutaline (3.6 mumol/kg) markedly increased the plasma insulin levels. Galanin (4.0 nmol/kg) completely abolished the insulin response to CCK-8 (p less than 0.001), but pancreastatin (4.0 nmol/kg) was without effect. Galanin inhibited the insulin response to terbutaline by approximately 60% (p less than 0.01), but pancreastatin inhibited the insulin response to terbutaline by approximately 35% only (p less than 0.05). CCK-8 and terbutaline did both elevate plasma glucagon levels by moderate potencies: neither pancreastatin nor galanin could affect these responses. Thus, in the mouse, galanin and pancreastatin both inhibit basal and stimulated insulin secretion, and stimulate basal glucagon secretion. Galanin is thereby more potent than pancreastatin. The study also showed that galanin potently inhibits insulin secretion stimulated by the octapeptide of cholecystokin and by the beta 2-adrenoceptor agonist terbutaline, and that pancreastatin inhibits terbutaline-induced insulin secretion.     

Inhibitory effect of somatostatin-28 on pancreatic polypeptide, glucagon and insulin secretion in normal man

We have compared the effects of equimolar doses of intravenous somatostatin-28 (SS-28) and somatostatin-14 (SS-14) (250 micrograms and 125 micrograms, respectively) on the secretion of pancreatic polypeptide (PP), glucagon and insulin evoked by a protein-rich meal in normal subjects. Both peptides reduced the fasting plasma levels of these hormones and completely abolished their responses to the alimentary stimulus; in addition, they caused an early decrease of plasma glucose followed by a hyperglycemic phase. As compared to SS-14, SS-28 elicited a longer-lasting inhibition of PP and insulin secretion and displayed greater hypo- and hyperglycemic effects. A somatostatin-like component, similar to SS-28, has been identified in pancreatic extracts as well as in peripheral plasma. Thus, it might be hypothesized that this peptide plays a role in the control of pancreatic hormone release.     

Gastric secretion and gastrin under progressive doses of somatostatin-14 and -28 administered intraperitoneally to the rat

The actions of progressive doses of intraperitoneally (IP) administered somatostatin-14 (SS-14) and -28 (SS-28) on gastric secretion (acid, pepsin) and mucosal blood flow (MBF) were studied in conscious gastric fistula rats both under basal conditions and under additional administration of pentagastrin. Also, somatostatin-like immunoreactivity was measured in aortal blood in all groups as well as aortal gastrin levels under basal conditions. IP infusion of equimolar doses of SS-14 and SS-28 resulted in an equal and dose-dependent inhibition of basal as well as pentagastrin-stimulated gastric acid secretion. MBF was reduced by either peptide both in the basal and pentagastrin experiments. Under basal conditions pepsin secretion was significantly increased by infusion of SS-14 at the higher doses, by infusion of SS-28 only at the intermediate dose (3.1 nmole kg-1.hr-1). In the pentagastrin experiments, low and intermediate doses of SS-14 tended to lower pepsin outputs but the highest dose of SS-14 stimulated pepsin secretion, whereas SS-28 had no effect on pepsin. Administration of SS-28 inhibited gastrin only at the highest dose (12.3 nmole kg-1.hr-1), and SS-14 had no influence at all on gastrin. After IP infusion of both peptides, plasma SLI rose dose-dependently under basal and stimulated conditions. Gel chromatography indicated an in-vivo conversion of SS-28 to SS-14 or intermediate fragments. It is concluded that SS-14 and SS-28 delivered by IP infusion, inhibit basal and stimulated gastric acid equally in the rat without suppressing gastrin. The mechanism underlying SS-mediated pepsin stimulation is unknown.     

Effects of hydrocortisone and aminophylline on plasma leukotriene C4 levels in patients during an asthmatic attack

To study the role of leukotriene C4(LTC4) and the effect of hydrocortisone and aminophylline on plasma LTC4 levels in patients with asthmatic attacks, we measured LTC4 in plasma of 18 asthmatics during a wheezing attack and of 7 normal subjects. Blood samples were obtained before and after treatment with aminophylline and/or hydrocortisone injections. We extracted LTC4 using a Sep-Pak C18 cartridge for the measurement of LTC4 by radioimmunoassay. The plasma levels of immunoreactive LTC4 (i-LTC4) of the normal subjects were 142 +/- 25 pg/ml (n = 7), while those of nonatopic type asthmatic patients with wheezing attacks were 208 +/- 68 pg/ml (n = 15) (p less than 0.01). Before and after treatment with both hydrocortisone succinate (100 mg) and aminophylline (250 mg), 6 asthmatic patients with wheezing attacks had a mean plasma level of i-LTC4 181 +/- 24 and 132 +/- 18 pg/ml (p less than 0.01), respectively. On the other hand, the treatment with aminophylline 250 mg alone increased the i-LTC4 levels from 178 +/- 19 pg/mg to 213 +/- 16 pg/mg (n = 6)(p less than 0.05), while treatment with hydrocortisone succinate 100 mg decreased the i-LTC4 level 0.05 from 284 +/- 99 pg/ml to 249 +/- 85 pg/ml (n = 4)(p less than 0.05). In conclusion, the present study shows that the i-LTC4 level in venous blood of patients with asthmatic attacks is decreased significantly by treatment with hydrocortisone succinate.