Glucagon secretion in chronic pancreatitis.

Plasma insulin, pancreatic glucagon and immunoreactive glucagon-like polypeptide of intestinal origin (enteroglucagon) have been measured in 10 patients with chronic pancreatitis and 5 normal subjects. Basal levels and changes following oral glucose (50 g) and an intravenous infusion of arginine (25 g in 30 min) have been studied. In patients with chronic pancreatitis the plasma insulin response to oral glucose and intravenous arginine was reduced. Basal pancreatic glucagon was increased in the patients and increased further with oral glucose. During an arginine infusion the pancreatic glucagon showed a brisk early increase greater than that seen in the normal subjects. Basal enteroglucagon levels were significantly increased in chronic pancreatitis but response to orla glucose and arginine infusion were little different from those seen in the normal subjects.     

Effect of maternal exercise on fetal liver glycogen late in gestation in the rat

To determine the effect of maternal exercise on fetal liver glycogen content, fed and fasted rats that were pregnant for 20.5 or 21.5 days were run on a rodent treadmill for 60 min at 12 m/min with a 0% grade or 16 m/min up a 10% grade. The rats were anesthetized by intravenous injection of pentobarbital sodium, and fetal and maternal liver and plasma samples were collected and frozen. Fetal liver glycogenolysis did not occur as a result of maternal exercise. Fetal blood levels of lactate increased 22-60%, but glucose, plasma glucagon, and insulin were unchanged during maternal exercise. Maternal liver glycogen decreased as a result of exercise in all groups of rats except the fasted 20.5-day-pregnant group. Plasma free fatty acids increased in all groups and blood lactate increased in fed (20.5 days) and fasted (21.5 days) pregnant rats. Maternal glucose, glucagon, and insulin values remained constant during exercise. The fetus appears to be well-protected from metabolic stress during moderate-intensity maternal exercise.     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.     

Metabolic and hormonal responses to cooling the fetal sheep in utero

The metabolic and hormonal effects of cooling 10 fetal sheep in utero (115-142 days of gestation) for 2h were studied. The fetal core temperature fell by 2.81 +/- 0.14 degrees C while the maternal temperature fell 0.86 +/- 0.15 degrees C. This hypothermia caused a significant rise in the fetal and maternal plasma glucose concentrations (P less than 0.001) and a fall in the fetal insulin concentrations (P less than 0.01). The fetal plasma lactate and cortisol concentrations rose rapidly (P less than 0.01) while the growth hormone fell (P less than 0.01) and remained low until cooling ceased when a rapid rebound occurred. There was no significant change in any of the fetal iodothyronines and no elevation of nonesterified free fatty acid concentrations, in contrast to the rapid rise (P less than 0.01) which occurred when newborn lambs were cooled. These observations demonstrate that appropriate glucose, insulin, lactate and cortisol responses to hypothermia have differentiated by 120 days of gestation. However, neither a thyroid hormone response nor an elevation in free fatty acid levels was observed. Thus not all components of the thermogenic response to hypothermia can be demonstrated in the late gestation fetail sheep in utero.     

Effect of pinealectomy on plasma glucose, insulin and glucagon levels in the rat

In an attempt to know the role of the pineal gland on glucose homeostasis, the blood plasma concentrations of glucose, insulin and glucagon under basal conditions or after the administration of nutrients were studied in the jugular vein of conscious pinealectomized (Pn), melatonin-treated pinealectomized (Pn + Mel) and control (C) rats. Glucose levels were smaller in C than in Pn rats, while immunoreactive insulin (IRI) concentrations were significantly greater in C than in Pn rats. Contrary to this, immunoreactive glucagon (IRG) levels were significantly greater in Pn than in C animals. Melatonin treatment of Pn rats induces an increase of IRI concentrations and a reduction in IRG levels. Similar changes were obtained when hormonal determinations were carried out in portal blood plasma. Although ether anesthesia increases circulating glucagon levels in the porta and cava veins, the qualitative changes of plasma insulin and glucagon in Pn and Pn + Mel were similar to those found in conscious rats. To determine the effects of nutrients on pancreatic hormone release, intravenous arginine or oral glucose were administered to the animals of the three experimental groups. In C rats, both glucose and IRI levels reached a peak 30 minutes after glucose ingestion, decreasing thereafter. However, in Pn rats a glucose intolerance was observed, with maximum glucose and insulin concentrations at 60 minutes, while in Pn + Mel animals, glucose and IRI concentrations were in between the data obtained with the other two groups. Furthermore, glucose ingestion induced a significant reduction of IRG levels in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of serum growth hormone levels by glucagon in patients with active acromegaly.

One mg of glucagon was given subcutaneously to eight patients with active acromegaly. Seven out of eight patients had a rapid decrease in serum growth hormone (GH) levels at 30 min after the glucagon injection. In two out of seven patients a rebound increase in serum GH following the early GH reduction was observed. On the other hand, oral administration of 50 g glucose which caused a comparable increase in blood glucose to that after the glucagon injection elicited no early suppression in serum GH levels in the same patients. These data suggest that the inhibition of GH release induced by glucagon could not be related to the increase in blood glucose by glucagon.     

Effects of hypersecretion of growth hormone and prolactin on plasma levels of glucagon and insulin in GH3-cell-tumor-bearing rats, and the influence of bromocriptine treatment

Plasma levels of prolactin, growth hormone, glucagon insulin and glucose were measured in non-treated control rats, bromocriptine-treated control rats and GH3-cell-tumor-bearing rats with and without bromocriptine treatment. Bromocriptine treatment increased plasma levels of glucagon, insulin and glucose in control rats. Tumor-bearing rats had increased body weight and increased plasma levels of prolactin, growth hormone, glucagon, insulin and glucose. Bromocriptine treatment reduced body weight and decreased the plasma levels of prolactin, glucagon and insulin, as compared to non-treated tumor-bearing rats. The drug had no effect on plasma levels of growth hormone and glucose. These results indicate that, in GH3-cell-tumor-bearing rats, prolactin, glucagon and insulin are more sensitive to the action of bromocriptine than growth hormone.     

Basal insulin, glucagon, and growth hormone replacement

Conclusions drawn from the pancreatic (or islet) clamp technique (suppression of endogenous insulin, glucagon, and growth hormone secretion with somatostatin and replacement of basal hormone levels by intravenous infusion) are critically dependent on the biological appropriateness of the selected doses of the replaced hormones. To assess the appropriateness of representative doses we infused saline alone, insulin (initially 0.20 mU.kg(-1).min(-1)) alone, glucagon (1.0 ng.kg(-1).min(-1)) alone, and growth hormone (3.0 ng.kg(-1).min(-1)) alone intravenously for 4 h in 13 healthy individuals. That dose of insulin raised plasma insulin concentrations approximately threefold, suppressed glucose production, and drove plasma glucose concentrations down to subphysiological levels (65 +/- 3 mg/dl, P < 0.0001 vs. saline), resulting in nearly complete suppression of insulin secretion (P < 0.0001) and stimulation of glucagon (P = 0.0059) and epinephrine (P = 0.0009) secretion. An insulin dose of 0.15 mU.kg(-1).min(-1) caused similar effects, but a dose of 0.10 mU.kg(-1).min(-1) did not. The glucagon and growth hormone infusions did not alter plasma glucose levels or those of glucoregulatory factors. Thus, insulin "replacement" doses of 0.20 and even 0.15 mU.kg(-1).min(-1) are excessive, and conclusions drawn from the pancreatic clamp technique using such doses may need to be reassessed.     

Studies on the growth of the fetal guinea pig. The effects of nutritional manipulation on prenatal growth and plasma somatomedin activity and insulin-like growth factor concentrations

In guinea pigs between days 41-46 of pregnancy prenatal growth has been manipulated by alteration of nutritional state. Three methods were used. Uterine artery ligation at day 30 of pregnancy depressed fetal growth rate by greater than 50% and was associated with falls in plasma insulin, IGF-1, cortisol, thyroid hormone, glucose, acetate and free fatty acid concentrations and rises in that of IGF-2, glucagon and amino acids. Fetal plasma was inhibitory to sulphate incorporation into pig costal cartilage. Complete food withdrawal from pregnant guinea pigs for 2 days at days 43-44 of pregnancy caused mild fetal growth retardation and similar changes in plasma constituents, except in that plasma IGF-2 concentrations were now depressed and plasma was not inhibitory to sulphate incorporation into pig costal cartilage. Production of hypoglycaemia by 4-times-daily maternal injections of glucose between days 41-46 of pregnancy accelerated fetal growth rate. It also elevated fetal plasma concentrations of insulin, IGF-1, IGF-2, sulphation-promoting activity, thyroid hormones, glucose and free fatty acids and depressed that of glucagon and amino acids. Fetal growth rate during the experimental period showed a good correlation with plasma glucose, insulin and IGF-1 and, to a certain extent, with sulphation-promoting activity. It did not correlate closely with fetal plasma IGF-2 concentration. Hepatic glycogen concentrations showed a good correlation with plasma IGF-2 levels.     

Muscle energetics during prolonged cycling after exercise hypervolemia

This study examined the question of whether increases in plasma volume (hypervolemia) induced through exercise affect muscle substrate utilization and muscle bioenergetics during prolonged heavy effort. Six untrained males (19-24 yr) were studied before and after 3 consecutive days of cycling (2 h/day at 65% of peak O2 consumption) performed in a cool environment (22-23 degrees C, 25-35% relative humidity). This protocol resulted in a 21.2% increase in plasma volume (P less than 0.05). During exercise no difference was found in the blood concentrations of glucose, lactate, and plasma free fatty acids at either 30, 60, 90, or 120 min of exercise before and after the hypervolemia. In contrast, blood alanine was higher (P less than 0.05) during both rest and exercise with hypervolemia. Measurement of muscle samples extracted by biopsy from the vastus lateralis muscle at rest and at 60 and 120 min of exercise indicated no effect of training on high-energy phosphate metabolism (ATP, ADP, creatine phosphate, creatine) or on selected glycolytic intermediate concentrations (glucose 1-phosphate, glucose 6-phosphate, fructose 6-phosphate, lactate). In contrast, training resulted in higher (P less than 0.05) muscle glucose and muscle glycogen concentrations. These changes were accompanied by blunting of the exercise-induced increase (P less than 0.05) in both blood epinephrine and norepinephrine concentrations. Plasma glucagon and serum insulin were not affected by the training. The results indicate that exercise-induced hypervolemia did not alter muscle energy homeostasis. The reduction in muscle glycogen utilization appears to be an early adaptive response to training mediated either by an increase in blood glucose utilization or a decrease in anaerobic glycolysis.     

Nippostrongylus brasiliensis: changes in plasma levels of gastrointestinal hormones in the infected rat

Plasma concentrations of gastrointestinal hormones were measured by radioimmunoassay in fasted rats 9 days after infection with a range of doses of Nippostrongylus brasiliensis. Values for infected rats fed ad libitum were compared with those of weight matched, pair fed, uninfected rats to control for the possible effects of dose-dependent reductions in food intake associated with infection. The plasma concentrations of some of the gastrointestinal hormones in infected rats were very different from those of their pair fed partners. The magnitude and direction of the changes varied according to the hormone being examined. Plasma concentrations of gastrin and pancreatic polypeptide were similar in pair fed and infected rats at all doses used. For the other hormones assayed, infection was associated with dose-related changes. The plasma concentrations of cholecystokinin and insulin were slightly but significantly reduced in infected rats. In contrast, secretin, enteroglucagon, and pancreatic glucagon concentrations were markedly increased. At the highest dose given (52 larvae/g body wt), the plasma levels of secretin and enteroglucagon in infected rats were elevated 9 X and 15 X, respectively. A comparison of the changes seen in N. brasiliensis-infected rats with those reported for other helminth infections revealed striking differences. The possible etiology of alterations in plasma gastrointestinal hormone concentrations and their contribution to the pathological changes seen in animals infected with helminths are discussed.     

Effect of different muscle shortening velocities during prolonged incremental cycling exercise on the plasma growth hormone, insulin, glucose, glucagon, cortisol, leptin and lactate concentrations.

BACKGROUND: Strenuous exercise was reported to involve the alteration in the release of some "stress" hormones such as growth hormone (GH), cortisol, catecholamines and appropriate adjustment of energy metabolism but the relative contribution of these hormones to metabolic response, to cycling exercise performed at different muscle shortening velocities, has not been clarified. AIMS: The purpose of this experiment was to assess the effect of applying different pedalling rates during a prolonged incremental cycling exercise test on the changes in the plasma levels of growth hormone, cortisol, insulin, glucagon and leptin in humans. Material and METHODS: Fifteen healthy non-smoking men (means +/- SD: age 22.9 +/- 2.4 years; body mass 71.9 +/- 8.2 kg; height 178 +/- 6 cm; with VO2max of 3.896 +/- 0.544 1 x min(-1), assessed in laboratory tests, were subjects in this study. The subjects performed in two different days a prolonged incremental exercise tests at two different pedalling rates, one of them at 60 and another at 120 rev x min(-1). During this tests the power output has increased by 30 W every 6 minutes. The tests were stopped when the subject reached about 70 % of the VO2max. RESULTS AND CONCLUSIONS: We have found that choosing slow or fast pedalling rates (60 or 120 rev min(-1)), while generating the same external mechanical power output, had no effect on the pattern of changes in plasma cortisol, insulin, glucagon, glucose and leptin concentrations. But, generation of the same external mechanical power output at 120 rev min(-1) causes more stepper increase (p < 0.01) in the plasma growth hormone concentration [GH]pl and plasma lactate concentrations [La]pl when compared to that observed during cycling at 60 rev x min(-1). We have also found that the onset of a significant increase in [GH]pl during cycling at 60 rev x min(-1) was not accompanied by significant increase in [La]pl. While during cycling at 120 rev x min(-1) the onset of a significant increase in [La]pl occurred without increase in [GH]pl, but with continuation of exercise when plasma [La]pl increased, there was also a parallel rise in plasma [GH]pl, as reported before. This results indicates that the increase in [GH]pl during exercise is not closely related to the increase in [La]pl.     

Plasma insulin and glucagon concentrations and biochemical variables in regularly menstruating females with ovulatory and anovulatory menstrual cycles.

Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations.     

Pituitary and extrapituitary effects of somatostatin in normal man.

The effects of synthetic linear somatostatin on basal circulating levels on several pituitary and pancreatic hormones, and of glucose and free fatty acids (FFA) were studied in 6 normal men after an overnight fast. A priming intravenous infusion of 250 mug of somatostatin in 18 sec was followed by a constant infusion of 500 mug over a period of 60 min. A decrease in plasma values of GH, prolactin, TSH, insulin and glucagon and in blood glucose was observed during somatostatin infusion, while FFA levels increased progressively. Plasma IRI and blood glucose increased rapidly when the somatostatin infusion was stopped, while FFA decreased progressively; GH, prolactin, TSH and glucagon remained low as compared to basal levels for one hour after the end of the infusion, i.e. until the end of the experiment. A slight but significant increase of LH and ACTH was observed after the end of the infusion.     

Hepatic glucagon clearance during insulin induced hypoglycemia

Studies concerning the importance of glucagon secretion in hypoglycemic counterregulation have assumed that peripheral levels of glucagon are representative of rates of pancreatic glucagon secretion. The measurement of peripheral levels of this hormone, however, may be a poor reflection of secretion rates because of glucagon's metabolism by the liver. Therefore, in order to understand the relationship between pancreatic glucagon secretion and levels of glucagon in the peripheral blood during hypoglycemia, we evaluated hepatic glucagon metabolism during insulin induced hypoglycemia. Four dogs received an insulin infusion to produce glucose levels less than 50 mg/dl for 45 minutes. In response to this, the delivery of glucagon to the liver increased from 36.7 +/- 5.9 ng/min in the baseline to 322.6 +/- 6.3 ng/min during hypoglycemia. Hepatic glucagon uptake increased proportionally from 13.6 +/- 7.2 ng/min to 103.1 +/- 28.3 ng/min and the percentage of delivered hormone that was extracted did not change (30.8 +/- 13.8% vs 32.9 +/- 11.6%). The absolute amount of glucagon metabolized by the liver was dependent on the rate of delivery and was not directly affected by plasma glucose level per se. To directly study the effect of hypoglycemia on hepatic glucagon metabolism, five dogs were given an exogenous infusion of somatostatin followed by an infusion of glucagon and then administered insulin to produce hypoglycemia. The percent of glucagon extracted by the liver (19.5 +/- 4.9% and 21.3 +/- 6.4%) was not affected by a fall in the plasma glucose level.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of hypophysectomy on pancreatic islet hormone and insulin-like growth factor I content and mRNA expression in rat

The growth arrest after hypophysectomy in rats is mainly due to growth hormone (GH) deficiency because replacement of GH or insulin-like growth factor (IGF) I, the mediator of GH action, leads to resumption of growth despite the lack of other pituitary hormones. Hypophysectomized (hypox) rats have, therefore, often been used to study metabolic consequences of GH deficiency and its effects on tissues concerned with growth. The present study was undertaken to assess the effects of hypophysectomy on the serum and pancreatic levels of the three major islet hormones insulin, glucagon, and somatostatin, as well as on IGF-I. Immunohistochemistry (IHC), in situ hybridization (ISH), radioimmunoassays (RIA), and Northern blot analysis were used to localize and quantify the hormones in the pancreas at the peptide and mRNA levels. IHC showed slightly decreased insulin levels in the cells of hypox compared with normal, age-matched rats whereas glucagon in cells and somatostatin in cells showed increase. IGF-I, which localized to cells, showed decrease. ISH detected a slightly higher expression of insulin mRNA and markedly stronger signals for glucagon and somatostatin mRNA in the islets of hypox rats. Serum glucose concentrations did not differ between the two groups although serum insulin and C-peptide were lower and serum glucagon was higher in the hypox animals. These changes were accompanied by a more than tenfold drop in serum IGF-I. The pancreatic insulin content per gram of tissue was not significantly different in hypox and normal rats. Pancreatic glucagon and somatostatin per gram of tissue were higher in the hypox animals. The pancreatic IGF-I content of hypox rats was significantly reduced. Northern blot analysis gave a 2.6-, 4.5-, and 2.2-fold increase in pancreatic insulin, glucagon, and somatostatin mRNA levels, respectively, in hypox rats, and a 2.3-fold decrease in IGF-I mRNA levels. Our results show that the fall of serum IGF-I after hypophysectomy is accompanied by a decrease in pancreatic IGF-I peptide and mRNA but by partly discordant changes in the serum concentrations of insulin and glucagon and the islet peptide and/or mRNA content of the three major islet hormones. It appears that GH deficiency resulting in a low IGF-I state affects translational efficiency of these hormones as well as their secretory responses. The maintenance of normoglycemia in the presence of reduced insulin and elevated glucagon serum levels, both of which would be expected to raise blood glucose, may result mainly from the enhanced insulin sensitivity, possibly due to GH deficiency and the subsequent decrease in IGF-I production.     

Diabetes mellitus secondary to idiopathic chronic calcifying pancreatitis in an adolescent woman

We describe the results of metabolic studies in a 17-year-old woman with diabetes mellitus which was the initial manifestation of idiopathic chronic calcifying pancreatitis (CCP). These studies were done on 2 occasions, 5 months and 5 years after the onset of diabetes, when her diabetes could be managed by glibenclamide and insulin, respectively. Five months after the onset of diabetes, oral glucose produced a small increase in insulin and a paradoxical rise in both glucagon immunoreactivity (GI) and growth hormone (GH). BY contrast, arginine-stimulated responses of the three hormones were normal. No increase in GI and a blunted rise in GH resulted from an insulin-induced decrease in blood glucose. Five years later, when CCP was demonstrated by roentogenologic examinations and tests of pancreatic exocrine function, oral glucose was followed by a flat and depressed response of C-peptide immunoreactivity and a markedly elevated response of gut glucagon-like-immunoreactivity (gut GLI). There were delayed and extremely low responses of pancreatic polypeptide to a test meal, irrespective whether or not her diabetes required treatment with insulin. These results demonstrate that CCP can cause diabetes in adolescents, as it does in adults, and that the adolescent woman described here had impaired responses of PP and gut GLI as well as insulin, GI and GH, especially to changes in blood glucose levels.     

Greater serum GH response to arm than to leg exercise performed at equivalent oxygen uptake

The aim of this study was to provide information concerning the mechanism of exercise-induced stimulation of growth hormone (GH) release in human subjects. For this reason serum GH as well as some hemodynamic variables and blood concentrations of noradrenaline (NA), insulin (IRI), lactate (LA), glucose (BG), and free fatty acids (FFA) were determined in seven healthy male subjects exercising on a bicycle ergometer with arms or legs and running on a treadmill at equivalent oxygen consumption levels. Significantly greater increases in serum GH concentration accompanied arm exercises than those observed during the leg exercises. This was accompanied by greater increases in heart rate, blood pressure, and plasma NA and blood lactate concentrations. Serum IRI decreased during both leg exercises and did not change during the arm exercise. There were no differences in BG and plasma FFA concentrations between the three types of exercise. The role of humoral and neural signals responsible for the greater GH response to arm exercise is discussed. The findings are consistent with the hypothesis that neural afferent signals sent by muscle "metabolic receptors" participate in the activation of GH release during physical exercise. It seems likely that the stimulation of these chemoreceptors is more pronounced when smaller muscle groups are engaged at a given work load. However, a contribution of efferent impulses derived from the brain motor centres to the control system of GH secretion during exercise is also possible.     

Ghrelin is suppressed by glucagon and does not mediate glucagon-related growth hormone release

BACKGROUND: Glucagon stimulation is routinely used as a provocative test to assess growth hormone (GH) sufficiency in pediatrics. Ghrelin also markedly stimulates GH secretion. Because glucagon stimulates the promoter of the ghrelin gene in vitro as well as ghrelin secretion by the perfused rat stomach, we sought to determine whether ghrelin mediates glucagon-induced GH secretion. METHODS: We compared ghrelin, GH, insulin and glucose responses following administration of 0.03 mg/kg intravenously (iv; max. 1 mg) and 0.1 mg/kg intramuscularly (im; max. 2 mg) of glucagon in two groups (n = 10-11/group) of GH-sufficient children. We also measured ghrelin before and 6 min after iv administration of 1 mg glucagon in 21 adult subjects. RESULTS: In children, glucagon caused a 26% decrease in ghrelin and a 72% increase in glucose concentrations that were independent of the dose or administration route of glucagon. In contrast, the insulin response was 2-3 times higher following administration of 0.1 mg/kg im compared to 0.03 mg/kg of glucagon iv. There was a significant correlation between the maximum decrease in ghrelin and increases in glucose (p = 0.03) but not in insulin. There was a significant correlation between ghrelin and GH area under the curve after controlling for the dose of glucagon (p = 0.03) but not for the maximum increase in glucose.In normal adults, glucagon administration caused a 7% decrease in ghrelin concentrations after 6 min (p = 0.0002). CONCLUSION: Ghrelin does not play a causal role in the GH response to pharmacological glucagon administration, which suppresses ghrelin levels starting a few minutes after injection.     

Hormonal studies in a patient with PP-producing tumors

Five years after the removal of pure pancreatic polypeptide (PP) producing tumors, concentrations of circulating levels of PP, insulin, glucagon, and growth hormone in the basal state, after insulin-induced hypoglycemia, and after a protein-rich meal were determined in a patient with previous truncal vagotomy and Billroth II gastrectomy. Basal plasma levels of PP ranged between 2180 and 2660 pg/ml suggesting persistence or recurrence of PP producing tumors. Concentrations of the other hormones were within normal values. After insulin injection (0.1 U/Kg) levels of PP and glucagon were not modified while those of GH rose from 3.2 to 22.6 ng/ml. After a protein meal (450 gms. of cooked ground beef meat) a sharp rise of plasma PP was observed to a peak of 11310 pg/ml at 10 min. Moreover, plasma levels of immunoreactive insulin also showed an equally prompt rise to a peak of 532 microU/ml while plasma glucagon rose simultaneously to 448 pg/ml. The cause of the abnormal PP, insulin and glucagon responses could not be ascertained but we postulate that they are derived from pancreatic tumors of mixed cell type.