Effect of medium-chain triglycerides and long-chain triglycerides on plasma pancreatic polypeptide secretion in man

Since it has been shown that stimulation of pancreatic enzyme secretion by triglycerides is dependent on the chain length of the fatty acids, we have studied whether the secretion of pancreatic polypeptide (PP) in response to triglycerides is also related to the chain length of the fatty acids. Therefore, the effect of equimolar amounts (60 mmol) of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on plasma PP was studied in 6 normal subjects. In the control study the subjects ingested 60 ml of 0.15 mol/l saline. Ingestion of LCT resulted in significant increases in plasma PP from 33 +/- 7 to 55 +/- 7 pmol/l (P less than 0.01), whereas both MCT and saline did not significantly increase plasma PP concentrations. Similarly, the integrated plasma PP secretion after LCT (1022 +/- 392 pmol/l per 90 min) was significantly greater than that after MCT (-690 +/- 358 pmol/l per 90 min; P less than 0.001) and that after saline (-462 +/- 205 pmol/l per 90 min; P less than 0.01). It is concluded that the secretion of PP in response to triglycerides is dependent on the chain length of the fatty acids.     

Naloxone and the ventilatory response to exercise in man

Endogenous opiate peptides are known to exert a depressant action on ventilation (VE), and their plasma levels have been shown to be elevated during a variety of exercise protocols. We investigated whether they might modulate the control of the hyperpnea of short-term constant-load (CLE) and incremental (IE) cycle-ergometer exercise. Four healthy subjects performed CLE tests at ca. 80% of the anaerobic threshold (theta an) for 5 min following a period of unloaded pedaling, and IE tests (10 or 20 W min-1) to the limit of tolerance. Normal saline (3 ml) or the opiate antagonist naloxone (1.2 mg in 3 ml) were administered intravenously prior to each test. Naloxone elicited no discernible effect on VE, alveolar gas tensions, or heart rate throughout the entire range of work rates; neither were theta an nor the maximum work rate affected. It is concluded that, for short-term exercise ranging in intensity from moderate to severe, the role played by endogenous opiate peptides in the control of the exercise hyperpnea appears to be negligible in man.     

Effect of truncal vagotomy on pancreatic polypeptide response after intravenous glucose administration

Intravenous glucose infusion was performed in six dogs with and without truncal vagotomy, and plasma pancreatic polypeptide (PP) responses were compared before and after truncal vagotomy. Following truncal vagotomy, basal PP levels decreased significantly from 286 ± 64 pg/ml (mean ± S.E.) to 94 ± 14 pg/ml (P < 0.05). Basal plasma insulin and blood glucose levels also tended to be lower, but not significantly. During the influsion of glucose, blood glucose concentrations rose rapidly in both groups and after 15 min reached peak values which were not significantly different from each other. In the vagotomized group the plasma insulin response to intravenous glucose infusion was significantly lower than in the control group. Following intravenous glucose loading, plasma PP concentrations decreased rapidly in both groups, but the PP level in the vagotomized group was suppressed only to 77 ± 4% of the basal level whereas in the control group it decreased to 45 ± 8%, significantly lower than in the vagotomized group (P < 0.01).These results suggest that basal PP is regulated by vagal tonus and that vagus controls, at least in part, suppression by intravenous glucose administration.     

Inflammatory response to strenuous muscular exercise in man

Based on the humoral and cellular changes occurring during strenuous muscular work in humans, the concept of inflammatory response to exercise (IRE) is developed. The main indices of IRE consist of signs of an acute phase response, leucocytosis and leucocyte activation, release of inflammatory mediators, tissue damage and cellular infiltrates, production of free radicals, activation of complement, and coagulation and fibrinolytic pathways. Depending on exercise intensity and duration, it seems likely that muscle and/or associated connective tissue damage, contact system activation due to shear stress on endothelium and endotoxaemia could be the triggering mechanisms of IRE. Although this phenomenon can be considered in most cases as a physiological process associated with tissue repair, exaggerated IRE could have physiopathological consequences. On the other hand, the influence of several factors such as age, sex, training, hormonal status, nutrition, anti-inflammatory drugs, and the extent to which IRE could be a potential risk for subjects undergoing intense physical training require further study.     

Stimulatory effect of intravenous calcium on pancreatic polypeptide secretion in man

In the present work we have examined the effect of i.v. calcium administration on the secretion of human pancreatic polypeptide (hPP) in normal subjects. The infusion of calcium glucono-galactono-gluconate, as to deliver 10 mg of calcium element per kilogram of body weight in two hours, was followed by a progressive elevation of plasma hPP which attained values two-fold those of the basal levels. This finding demonstrates that calcium behaves as a pancreatic polypeptide secretagogue in man.     

Roles of pancreatic polypeptide in regulation of food intake

Pancreatic polypeptide (PP) is produced in pancreatic islets of Langerhans and released into the circulation after ingestion of a meal. Peripherally administered PP suppresses food intake and gastric emptying. On the other hand, central administration of PP elicits food intake and gastric emptying. Therefore, PP actions on food intake may be, in part, attributable to gastric emptying. PP transgenic mice exhibit decreases in both food intake and gastric emptying rate that were clearly reversed by anti-PP antiserum. PP is an anorexigenic signal in the periphery and an orexigenic signal in the central nervous system.     

Impaired pancreatic polypeptide response to insulin hypoglycemia in obese subjects

We have studied the effect of insulin hypoglycemia on the secretion of pancreatic polypeptide (PP) in 14 obese subjects with normal glucose tolerance and in 6 normal controls. Infusion of insulin 0.1 U/kg/h in controls and 0.12 U/kg/h in the obese, for one hour, produced a progressive hypoglycemia, similar in both groups (nadir 2 mmol/l at 50 min). The secretion of PP was less in obese subjects than in controls (peak 116 mmol/l vs 184 pmol/l, P less than 0.01) (integrated secretion sigma delta PP 288 vs 472 pmol/l, P less than 0.01) and was also delayed in the obese subjects beginning at 50 min instead of 40 min. The secretion of glucagon and of C-peptide were not different in the two groups, but the integrated response of ACTH was higher in the obese (sigma delta ACTH 52 pmol/l vs 25 pmol/l, P less than 0.01). The secretory response of growth hormone (STH) was smaller in the obese group (peak 8.6 +/- 1.28 vs 21.4 +/- 6.4 ng/ml, P less than 0.01). The reduced secretion of PP in obese subjects could be due to impaired sensitivity to hypoglycemia of the central control mechanism for PP release. The similarity of the reductions in the secretion of both PP and STH support this hypothesis, although a reduction in the secretory capacity of pancreatic PP cells cannot be excluded.     

Evidence for dopaminergic modulation of pancreatic polypeptide secretion in man

This study examines the role of dopaminergic mechanisms in the regulation of human pancreatic polypeptide (hPP) secretion in 11 normal male volunteers. Administration of domperidone (20 mg iv), an extracerebral inhibitor of dopamine receptors, resulted in a hPP rise (p<0.05) within 10 min and a peak response (p<0.01) at 15 min after drug administration. Administration of the dopaminergic agonist, bromocriptine, 2.5 mg tid for 4 days eliminated hPP responses to isometric handgrip exercise in these 11 volunteers. These results suggest that dopaminergic mechanisms may exert a tonic inhibitory effect on hPP secretion in normal subjects.     

Effect of neurotensin on pancreatic function in man

The effect of neurotensin on submaximally-stimulated hepatobiliary and pancreatic secretion was studied in 6 healthy subjects. An intravenous infusion of neurotensin 1.4 ± 0.3 pmol/kg/min, designed to reproduce plasma neurotensin immunoreactivity levels within the physiological range, produced a significant increase in pancreatic bicarbonate output. Plasma concentrations of pancreatic polypeptide rose by 83 ± 16 pmol/l and were associated with a small reduction in trypsin, but no significant change in bilirubin outputs.     

Effect of glycogen depletion on the ventilatory response to exercise

Five male subjects performed two graded exercise studies, one during control conditions and the other after reduction of muscle glycogen content by repeated maximum exercise and a high fat-protein diet. Reduction in preexercise muscle glycogen from 59.1 to 17.1 mumol X g-1 (n = 3) was associated with a 14% reduction in maximum power output but no change in maximum O2 intake; at any given power output O2 intake, heart rate, and ventilation (VE) were significantly higher, CO2 output (VCO2) was similar, and the respiratory exchange ratio was lower during glycogen depletion compared with control. The higher VE during glycogen depletion was associated with a higher VE/VCO2 ratio, lower end-tidal and mixed venous CO2 partial pressures, and higher blood pH than in the control studies. Changes in exercise VE accompanying glycogen depletion were not explained by changes in CO2 flux to the lungs suggesting that other factors served to modulate VE in these experimental conditions.     

Effect of adding albumin to solutions of cholecystokinin on pancreatic protein output and pancreatic polypeptide release

In four conscious dogs with chronic gastric and pancreatic Thomas fistulas we studied the effect of 99% pure cholecystokinin-33 (CCK-33) solutions on pancreatic secretion and PP release. CCK-33 was dissolved in 0.154 M NaCl alone or in the same solution containing 1 g per 100 ml dog albumin. The response of pancreatic protein output to increasing doses of CCK-33 (0.5, 1, 2, 4 IDU/kg per h) was significantly $\text{(P < 0.05)}$ higher when CCK was dissolved in NaCl with albumin than in NaCl alone. These results were confirmed by measuring CCK immunoreactivity in samples from tips of infusion lines by a gastrin radioimmunoassay. Release of pancreatic polypeptide (PP) following increasing doses of CCK-33 was also significantly $\text{(P < 0.05)}$ elevated when CCK was dissolved in an albumin-containing solution. There was a significant $\text{(P < 0.02)}$ correlation between plasma concentrations of PP and pancreatic protein output.This study suggests that albumin should be added to CCK-33 solutions to preserve biological activity. The biological effect of CCK-33 may be substantially underestimated if albumin is omitted.     

Effect of training on cardiovascular response to exercise in women.

Seventeen women (mean age 31 yr) participated in a training program divided into an initial 9-wk period and a subsequent 52-wk period, during which time 6 continued to exercise and the remainder detrained. Improvements in VO2max were significant (+34%) during the initial 9 wk and small (+5%) for the final 52 wk. Four women who stopped training showed a decrease in VO2max (-10%) during the last phase. During the initial 9 wk, central adaptation was important, with SV showing an increase of 28% at 80% VO2max. Peripheral adaptation (a-v O2 difference) was unchanged. Subjects who trained an additional 52 wk showed a slight drop in SV at submaximal work loads from the initial increase following the first 9 wk. When compared with the initial test the change at 9 wk in peripheral adaptation was a small and nonsignificant rise, followed by a significant increase at 61 wk. Women who are very unfit initially (predicted VO2max of 28 ml/kg-min), apparently adapt to the initial training with a central change followed by a much stronger peripheral adaptation during a longer training program.     

Effect of lowered muscle temperature on the physiological response to exercise in men

The effect of low muscle temperature on the response to dynamic exercise was studied in six healthy men who performed 42 min of exercise on a cycle ergometer at an intensity of 70% of their maximal O2 uptake. Experiments were performed under control conditions, i.e. from rest at room temperature, and following 45 min standing with legs immersed in a water bath at 12 degrees C. The water bath reduced quadriceps muscle temperature (at 3 cm depth) from 36.4 (SD 0.5) degrees C to 30.5 (SD 1.7) degrees C. Following cooling, exercise heart rate was initially lower, the mean difference ranged from 13 (SD 4) beats.min-1 after 6 min of exercise, to 4 (SD 2) beats.min-1 after 24 min of exercise. Steady-state oxygen uptake was consistently higher (0.2 l.min-1). However, no difference could be discerned in the kinetics of oxygen uptake at the onset of exercise. During exercise after cooling a significantly higher peak value was found for the blood lactate concentration compared to that under control conditions. The peak values were both reached after approximately 9 min of exercise. After 42 min of exercise the blood lactate concentrations did not differ significantly, indicating a faster rate of removal during exercise after cooling. We interpreted these observations as reflecting a relatively higher level of muscle hypoxia at the onset of exercise as a consequence of a cold-induced vasoconstriction. The elevated steady-state oxygen uptake may in part have been accounted for by the energetic costs of removal of the extra lactate released into the blood consequent upon initial tissue hypoxia.