Effects of hyperglycemia and hyperinsulinemia on satiety in humans.

Hyperglycemia may influence satiety. One mechanism by which glucose could influence food intake is hyperinsulinemia. Therefore, we investigated the short-term effects of acute hyperglycemia and euglycemic hyperinsulinemia on satiety. Six healthy volunteers (aged 20 to 26 years) were studied for 240 minutes on three separate occasions in random order during (1) intravenous (i.v.) saline (control), (2) acute hyperglycemic hyperinsulinemia (HG) with plasma glucose at 15 mmol/L, and (3) euglycemic hyperinsulinemia (HI) with plasma insulin at 80 mU/L and glucose at 4 to 5 mmol/L. Subjective criteria for appetite like the wish to eat, prospective feeding intentions ("How much food do you think you can eat?"), and feelings of hunger and fullness were scored on a 100-mm visual analog scale (VAS) at 30-minute intervals. Appetite was also measured every 60 minutes with the use of a food selection list (FSL). Appetite (prospective feeding intentions, feelings of hunger, and the wish to eat) gradually increased over basal levels during control conditions and HI. In contrast, prospective feeding intentions and feelings of hunger gradually decreased during HG and were significantly (P < .05) reduced versus basal and control levels during the last hour of the experiment. The wish to eat followed the same pattern. Feelings of fullness did not significantly change in all three experiments. Total food selection was not significantly decreased during HG, but the preference for fat-rich or carbohydrate-rich items tended to be reduced. The study suggests that in humans hyperglycemia induces satiety. This effect seems not to be mediated by insulin, since HI had no effect on appetite. However, a potentiating effect of endogenous insulin on the satiating effect of high blood glucose levels cannot be excluded.

Cholecystokinin secretion in patients with chronic pancreatitis and after different types of pancreatic surgery.

UNLABELLED: Cholecystokinin (CCK) secretion may be affected in patients with chronic pancreatitis (CP), but little is known on the effect of pancreatic surgery on CCK secretion. We measured CCK secretion (radioimmunoassay, RIA) in response to bombesin infusion (100 ng/kg/20 min) for 120 min to test CCK secretory capacity, to ingestion of a liquid diet (400 kcal) for 120 min, and in response to a solid fat-rich meal (500 kcal) for 120 min. These studies were performed in 45 patients with CP (25 with exocrine insufficiency), 15 patients after duodenum-preserving pancreatic head resection (DPRHP), 18 patients after the Whipple operation, 12 patients after distal pancreatectomy (DP), and 35 control subjects. In CP patients, the CCK secretory capacity was preserved, but the postprandial CCK response was reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after Whipple's operation, CCK secretory capacity and postprandial CCK secretion were significantly (p < 0.05) reduced. In patients after DPRHP, CCK secretory capacity was not affected, but the postprandial CCK response was significantly (p < 0.05) reduced, depending on meal composition and the presence of exocrine insufficiency. In patients after DPRHP, fasting plasma CCK levels were significantly (p < 0.01) increased, pointing to the absence of feedback inhibition on CCK secretion by intraluminal enzymes. After DP, the CCK secretory capacity was not affected. IN CONCLUSION: alterations in CCK secretion are observed in patients with chronic pancreatitis and after pancreatic surgery. These alterations are related not only to the disease process (exocrine insufficiency) but also to the type of surgery and type of stimulus.

Intrinsic properties of the developing motor cortex in the rat: in vitro axons from the medial somatomotor cortex grow faster than axons from the lateral somatomotor cortex.

The axons that originate in the medial somatomotor cortex of the rat depart, during development, after those from the lateral somatomotor cortex, yet they arrive in the cervical spinal cord first. Either the medially originating axons elongate faster, or the laterally originating ones pause along the descent pathway. To investigate the presence of an intrinsic difference of the axonal elongation velocity between the lateral and medial somatomotor cortical areas, we cultured explants taken from these areas for 2 days, and measured the length of the outgrowth. After 2 days the explants were surrounded by a radiate corona of axons of which the longest measured 1.95 mm. A significant difference was detected between the medial and lateral somatomotor cortical areas in vitro. Axons originating from explants taken from the medial somatomotor cortical area are, after 2 days in culture, on average 0.16 mm longer than those from the lateral somatomotor cortical area. Though the observed difference is not large enough to allow for the overtaking observed in vivo, it does indicate that intrinsic differences exist within the developing rat somatomotor cortex. This in turn indicates that intrinsic cortical traits not only influence regionalization and targeting behavior of cortical projection neurons, but also their axonal elongation speed.

Medium chain triglycerides activate distal but not proximal gut hormones.

BACKGROUND AND AIMS: Compared to long chain triglycerides (LCT), medium chain triglycerides (MCT) are considered an attractive caloric source in malabsorptive diseases because of their favorable physico-chemical characteristics. The use of MCTis, however, limited by the occurrence of gastrointestinal symptoms such as diarrhoea. We have, therefore, investigated the effects of MCT and LCT on proximal (cholecystokinin; CCK) and distal (peptide YY; PYY) gut hormone secretion. METHODS: Eight healthy volunteers participated in four experiments performed in random order during continuous intraduodenal administration for 360 min of a) saline (control); b) LCT15 mmol/h; c) MCT15mmol/h (equimolar); d) MCT 30 mmol/h (equicaloric). Plasma CCK and PYY were determined at regular intervals (radioimmunoassay). Duodenocecal transit (DCTT) was measured by lactulose H(2)breath test. RESULTS: DCTT during LCT (105 +/- 11 min) was not significantly different from saline (111 +/- 10 min). Both low dose MCT (54 +/- 5 min) and high dose MCT (61 +/- 6 min) significantly accelerated DCTT (P< 0.05). Plasma CCK increased significantly (P< 0.05) during LCT but not during MCT or saline. PYY increased significantly (P< 0.05) not only during LCT, but also during low and high dose MCT but not during saline. CONCLUSIONS: Intraduodenal MCTs a) accelerate intestinal transit; b) do not stimulate CCK release; c) but stimulate release of the distal gut hormone PYY. These results suggest that MCTs are not rapidly absorbed in the proximal gut but probably reach the ileocolonic region and stimulate PYY release.

Is the effect of acute hyperglycaemia on interdigestive antroduodenal motility and small-bowel transit mediated by insulin?

Acute hyperglycaemia inhibits antroduodenal motility. In non-diabetic subjects this inhibitory effect may result from reactive endogenous hyperinsulinaemia. Therefore, we investigated the effects of hyperinsulinaemia during both hyperglycaemia and euglycaemia on interdigestive antroduodenal motility (perfusion manometry) and duodenocaecal transit time (DCTT; lactulose breath-H2 test). Six healthy volunteers (age 20-26 years) were studied for 240 min on three separate occasions in random order during: (a) i.v. saline (control); (b) acute hyperglycaemic hyperinsulinaemia (HG) with plasma glucose at 15 mmolL-1; and (c) euglycaemic hyperinsulinaemia (HI) with plasma insulin at 80 mUL-1 and glucose at 4-5 mmolL-1, RESULTS: DCTT was significantly (P < 0.05) prolonged during HG (158 +/- 23 min) compared with control (95 +/- 25 min), whereas HI had no effect (100 +/- 17 min). Mean duration of complete migrating motor complex (MMC) cycles was significantly (P < 0.05) reduced during HG (63 +/- 9 min) compared with control (103 +/- 15 min) and HI (105 +/- 16 min), which resulted from a significantly (P < 0.05) shorter duration of phase II. Antral motility was significantly (P < 0.05) reduced during both HI (20 +/- 8 contractions 240 min-1) and HG (9 +/- 5) compared with control (43 +/- 7). It is concluded that in healthy subjects hyperglycaemia prolongs DCTT, increases duodenal MMC cycle frequency and inhibits antral motility. Hyperinsulinaemia reduces antral motor activity but has no effect on interdigestive duodenal motility or DCTT. Thus, other factors, apart from insulin, mediate the inhibitory effect of hyperglycaemia on interdigestive intestinal motility and transit.

Effects of medium-chain and long-chain triglycerides on antroduodenal motility and small bowel transit time in man.

UNLABELLED: Medium-chain triglycerides are known to induce diarrhea, possibly resulting from accelerated intestinal transit. We performed antroduodenal manometry and lactulose hydrogen breath testing simultaneously in eight healthy subjects in order to determine the effects of intraduodenally administered medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on gastrointestinal motility and small bowel transit time. LCT (15 mmol/hr) induced a fed motor pattern. In contrast, during MCT, in both equimolar (15 mmol/hr; MCT-1) and equicaloric (30 mmol/hr; MCT-2) amounts comparable to LCT, interdigestive motility was preserved but with a significantly (P < 0.05) shorter MMC cycle length (MCT-1, 65 +/- 7 min; MCT-2, 53 +/- 6 min) compared to control (saline infusion; 127 +/- 14 min). Duodenocecal transit time (DCTT) was significantly (P < 0.05) accelerated during administration of MCT (MCT-1, 56 +/- 6 min; MCT-2, 69 +/- 9 min) and was not affected by LCT (105 +/- 13 min) when compared to control (101 +/- 9 min). IN CONCLUSION: MCT, in contrast to LCT, preserve interdigestive motility with a shorter MMC cycle length and accelerate DCTT.

Effect of gastrin on antroduodenal motility: role of intraluminal acidity.

The effect of gastrin on the migrating motility complex (MMC) was studied in seven healthy subjects. It was hypothesized that a potential effect of gastrin on the MMC may result from intraluminal acidification through increased gastric acid secretion. Therefore, antroduodenal manometry and intraluminal acidity were recorded simultaneously. The effect of gastric acid inhibition, with and without administration of gastrin, on antroduodenal motility and intraluminal acidity was also evaluated and compared with saline infusion (control). Continuous infusion of gastrin-17 (20 pmol. kg-1. h-1) increased intragastric and intraduodenal acidity and suppressed phase II and phase III motor activity in both antrum and duodenum. Concomitant gastric acid inhibition with intravenous famotidine, as demonstrated by intragastric neutralization of pH, completely antagonized the effect of gastrin on the MMC. In fact, famotidine infusion, both with and without administration of gastrin, significantly shortened MMC cycle length. It is concluded that the effect of gastrin on interdigestive antroduodenal motility results from increased intraluminal acidity.

Pancreatic polypeptide secretion in patients with chronic pancreatitis and after pancreatic surgery.

AIM: We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. METHODS: Included were patients with CP without (n = 20) and with (n = 30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n = 20), after Whipple's procedure (n = 19), following distal pancreatectomy (DP; n = 12), and healthy controls (n = 36). RESULTS: In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01-0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01-0.05) reduced. CONCLUSION: Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).