W. F. Lam

Effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure in humans

The effect of acute hyperglycemia on esophageal motility and lower esophageal sphincter pressure (LESP) was investigated. Esophageal manometry was performed for 120 minutes in seven healthy volunteers on two separate occasions during euglycemia and during hyperglycemia with blood glucose levels stabilized at 15 mmol/L. At 90 minutes, motility was stimulated with edrophonium chloride (0.08 mg/kg intravenously). Pancreatic polypeptide (PP) secretion was determined as an indirect measure of vagal-cholinergic tone. During hyperglycemia the LESP decreased significantly (P less than 0.05) from 20.1 +/- 1.6 mm Hg to 10.7 +/- 0.6 mm Hg; plasma PP levels were also significantly (P less than 0.05) decreased during hyperglycemia. Edrophonium induced significant (P less than 0.05) increases in LESP and PP levels in both experiments. However, LESP and PP levels after edrophonium stimulation remained significantly (P less than 0.05) reduced during hyperglycemia compared with euglycemia. During hyperglycemia a significant (P less than 0.05) increase in peristaltic wave duration and a decrease in peristaltic velocity were observed in the distal part of the esophagus. It is concluded that blood glucose levels affect esophageal motility, acute hyperglycemia reduces LESP and impairs esophageal motility under both basal and edrophonium-stimulated conditions, and hyperglycemia reduces plasma PP levels, suggesting impaired vagal-cholinergic activity during hyperglycemia.

Effect of insulin on basal and cholecystokinin-stimulated gallbladder motility in humans

BACKGROUND/AIMS Acute hyperglycemia inhibits gallbladder contraction. In non-diabetic subjects this inhibitory effect may result from endogenous hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin-stimulated gallbladder motility. METHODS Gallbladder volume (ultrasonography) and duodenal bilirubin output were studied simultaneously in nine healthy volunteers (age 20-52 years) on 3 separate occasions in random order during: (a) saline infusion (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mmol/l), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/l, glucose at 4-5 mmol/l). After a 2-h basal clamp period, cholecystokinin was infused intravenously for 60 min at 0.25 IDU x kg(-1) x h(-1), followed by another 60 min at 0.5 IDU x kg(-1) x h(-1). RESULTS HI and HG significantly (p<0.05) reduced basal duodenal bilirubin output compared to control, while basal gallbladder volume did not change. At the low dose cholecystokinin, gallbladder emptying during HG (25+/-3%) and HI (39+/-4%) was significantly (p<0.01) reduced compared to control (61+/-4%). The inhibitory effect of HG was significantly (p<0.05) stronger compared to HI. Duodenal bilirubin output during the low dose cholecystokinin was significantly (p<0.05) reduced by HG, but not by HI. No inhibitory effect of HG and HI on gallbladder emptying and duodenal bilirubin output was observed with the high dose of cholecystokinin. CONCLUSIONS In healthy subjects acute hyperglycemia and euglycemic hyperinsulinemia reduce basal duodenal bilirubin output and inhibit gallbladder emptying stimulated by low dose cholecystokinin. These results suggest that insulin is involved in the inhibitory effect of hyperglycemia on basal and cholecystokinin-stimulated gallbladder motility.

Hyperglycemia Modulates Gallbladder Motility and Small Intestinal Transit Time in Man

The aim of the present study was to investigate the effect of acute hyperglycemia on (1) the intestinal phase of gallbladder contraction induced by the intraduodenal administration of emulsified fat, and (2) the small intestinal transit time measured by the lactulose breath hydrogen test. Six healthy volunteers were studied in random order during normoglycemia and hyperglycemia (blood glucose levels 15 mmol/liter). Gallbladder volumes were measured with ultrasonography. Administration of 1 and 2 g/hr of fat resulted in significant reductions in gallbladder volumes from 24±2 cm3 to 11±1 cm3 (P<0.05) and 8±1 cm3 (P<0.05), respectively during normoglycemia, and from 24±2 cm3 to 21±2 cm3 (P<0.05) and 16±2 cm3, respectively (P<0.05) during hyperglycemia. Compared to normoglycemia, the gallbladder contraction was significantly (P<0.05) reduced during hyperglycemia. No significant differences in CCK secretion were observed between experiments. Small intestinal transit time during hyperglycemia (101±12 min) was significantly (P<0.05) prolonged compared to normoglycemia (57±12 min). During hyperglycemia, basal PP levels and PP secretion in response to intraduodenal fat were significantly (P<0.05) reduced compared to normoglycemia. It is concluded that (1) low doses of intraduodenal emulsified fat result in significant gallbladder contraction and CCK secretion, (2) acute hyperglycemia inhibits intraduodenal fat induced gallbladder contraction, (3) acute hyperglycemia does not affect the intraduodenal fat induced CCK secretion, (4) small intestinal transit is significantly prolonged during acute hyperglycemia, and (5) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Hyperglycemia Reduces Gastric Secretory and Plasma Pancreatic Polypeptide Responses to Modified Sham Feeding in Humans

We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 +/- 1.0 mmol/h) was not significantly different from euglycemia (5.4 +/- 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 +/- 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 +/- 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 +/- 95 pmol/l.90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 +/- 71 pmol/l.90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia.

Effect of hyperglycaemia on gallbladder motility in Type 1 (insulin-dependent) diabetes mellitus

SummaryPatients with diabetes mellitus are at increased risk of developing gallstones. This has been attributed, among other factors, to alterations in gallbladder motility in the presence of autonomic neuropathy. Since high blood glucose concentrations impair gastric emptying in diabetic patients, we have investigated the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin-dependent) diabetic patients were studied twice during euglycaemia (blood glucose 5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique. In addition, seven healthy volunteers were studied during euglycaemia and hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied before and during infusion of step-wise increasing doses of cholecystokinin-33, 0.25, 0.5 and 1.0 Ivy Dog Unit · kg−1 · h−1, each dose for 30 min. Mean basal gallbladder volumes were not significantly different in the four experiments. Administration of cholecystokinin resulted in significant (p<0.05) dose-dependent reductions in gallbladder volume in all experiments. During euglycaemia the gallbladder contraction in diabetic patients was not significantly different from the control subjects. During hyperglycaemia the gallbladder contraction in the diabetic patients was significantly (p<0.05) reduced compared to euglycaemia only during infusion of 0.25 Ivy Dog Unit · kg−1 · h−1 of cholecystokinin (19±6% vs 33±6%). Compared to euglycaemia, during hyperglycaemia the gallbladder contraction in the control subjects was significantly (p<0.05) reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit · kg−1 · h−1 of cholecystokinin (14±4% vs 31±3%; 42±6% vs 65±5%; 74±4% vs 90±3%, respectively). It is concluded that during euglycaemia the gallbladder contraction in response to cholecystokinin in Type 1 diabetic patients is not significantly different from control subjects. During hyperglycaemia the gallbladder contraction in response to 0.25 Ivy Dog Unit · kg−1 · h−1 cholecystokinin, leading to cholecystokinin levels as observed after ingestion of a light meal, is significantly reduced in Type 1 diabetic patients.

Effect of Insulin and Glucose on Basal and Cholecystokinin-Stimulated Exocrine Pancreatic Secretion in Humans

Pancreaticobiliary secretion is reduced during acute hyperglycemia. In nondiabetics, this inhibitory effect also may result from hyperinsulinemia. Therefore we investigated the effects of acute hyperglycemia and euglycemic hyperinsulinemia on basal and cholecystokinin (CCK)-stimulated pancreaticobiliary secretion. Nine healthy volunteers (age, 22-52 years) were studied on three occasions in random order during (a) intravenous saline (control), (b) hyperglycemic hyperinsulinemic clamping (HG; plasma glucose at 15 mM), and (c) euglycemic hyperinsulinemic clamping (HI; plasma insulin at 150 mU/L, glucose at 4-5 mM). Duodenal outputs of bilirubin, amylase, trypsin, and bicarbonate were measured under basal conditions and during CCK infusion (0.25 and 0.5 IDU/kg/h). Basal pancreaticobiliary secretion was significantly (p < 0.05) reduced during both HG and HI. During low-dose CCK stimulation, HG significantly (p < 0.05) reduced bilirubin and trypsin output compared with control. In contrast, HI did not significantly reduce pancreatic enzyme and bilirubin output during low-dose CCK infusion. During high-dose CCK infusion, neither HI nor HG influenced pancreatic enzyme and bilirubin output. Pancreatic bicarbonate output was not influenced by CCK and remained significantly (p < 0.05) reduced during HI and HG compared with control. It is concluded that during both acute hyperglycemia and euglycemic hyperinsulinemia, basal pancreaticobiliary secretion is significantly reduced. CCK-stimulated pancreatic enzyme and bilirubin output is significantly reduced only during hyperglycemia. The inhibitory effect of hyperglycemia on pancreaticobiliary secretion in healthy volunteers may occur independent of insulin.

Effects of Parenteral Nutrients on Gastrointestinal Motility and Secretion

BACKGROUND The stimulation of gastrointestinal motility and secretion during nutrient digestion is generally divided into a cephalic, gastric and intestinal phase. Little is known about the effects of macronutrients on gastrointestinal function during the postabsorptive or circulatory phase of digestion. METHODS Review of studies investigating the effects of circulating macro-nutrients such as fat, amino acids and glucose on gastrointestinal motility and secretion. RESULTS Intravenous infusion of fat emulsions delays gastric emptying and interrupts the interdigestive intestinal motor pattern. Intravenous amino acids, administered in high doses, stimulate gastric acid secretion, pancreatic secretion, gallbladder contraction, and intestinal motility. Patients receiving total parental nutrition (TPN) have inert gallbladders and are at risk of developing gallbladder sludge and stones. Administering a proportion of the daily amino acid requirement by rapid intravenous infusion may prove useful in the prevention of sludge and stone formation during TPN by promoting gallbladder contraction. Intravenous infusion of glucose, already at physiological postprandial plasma levels, inhibits gastrointestinal motility and secretion. The inhibitory effect of glucose is dose-dependent, that is, more pronounced at higher plasma glucose levels. Recent studies have indicated that in patients with diabetes mellitus alterations in gastrointestinal function are related to the degree of hyperglycaemia. CONCLUSIONS Nutrients during the circulatory phase of digestion influence gastrointestinal motility and secretion. Knowledge of these effects is relevant for conditions with increased plasma levels of macro-nutrients such as in patients with diabetes mellitus or during total parenteral nutrition.

Effect of intravenous glucose on intravenous amino acid-induced gallbladder contraction and CCK secretion

The present study was undertaken to investigate the effect of acute hyperglycemia on the gallbladder contraction induced by intravenous administration of high doses of amino acids (Vamin 18, 250 mg protein/kg/hr). Six healthy volunteers were studied in random order on two occasions during normoglycemia and hyperglycemia with blood glucose levels stabilized at 15 mmol/liter. Gallbladder volumes, measured with ultrasonography, were studied for 60 min before and for 120 min during intravenous infusion of amino acids (IVAA). Administration of IVAA resulted in a significant reduction (P<0.05) in gallbladder volume from 32±5 cm3 to 17±2 cm3 during normolgycemia. During hyperglycemia no significant changes in gallbladder volume were observed in response to IVAA. No significant changes in plasma CCK concentration, the major hormonal stimulus for gallbladder contraction, occurred in response to IVAA. During hyperglycemia, pancreatic polypeptide (PP) secretion, as an indirect measure of vagal cholinergic tone, in response to IVAA was significantly (P<0.05) reduced compared to normoglycemia. It is concluded that: (1) administration of high doses of IVAA results in significant gallbladder contraction, (2) high doses of IVAA do not stimulate CCK secretion, (3) acute hyperglycemia inhibits IVAA-induced gallbladder contraction, and (4) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.

Effect of acute hyperglycemia on basal and cholecystokinin stimulated exocrine pancreatic secretion in humans

This study was undertaken to investigate the effect of acute hyperglycemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of bilirubin, amylase, trypsin and bicarbonate were measured by aspiration using a recovery marker under basal condition for 75 min and during continuous infusion of CCK (0.5 IDU/kg.h for 60 min). Seven healthy subjects participated in two experiments performed in random order during normoglycemia and during acute hyperglycemic clamping at 15 mmol/l. At regular intervals plasma PP levels were determined as an indirect measure of vagal-cholinergic tone. Basal pancreatico-biliary secretion was significantly (p<0.05) reduced during acute hyperglycemia. CCK significantly (p<0.05) increased bilirubin, amylase and trypsin output both during normo- and hyperglycemia. During the initial 30 min of CCK infusion the bilirubin, amylase and trypsin outputs were significantly (p<0.05) inhibited in the hyperglycemic experiment compared to normoglycemia. In the following 30 min of CCK infusion the bilirubin, amylase and trypsin output were not different between hyper- and normoglycemia. Basal and CCK-stimulated plasma PP concentrations were significantly (p<0.05) reduced during hyperglycemia. In summary: 1) basal pancreatico-biliary secretion is significantly reduced during acute hyperglycemia 2) during hyperglycemia CCK-stimulated pancreatico-biliary secretion is also significantly reduced with the pattern of a delayed response 3) hyperglycemia inhibits basal and CCK-stimulated PP secretion suggesting impaired vagal-cholinergic activity during hyperglycemia.

Influence of hyperglycemia on the satiating effect of CCK in humans

In the present study the effects of intraduodenal (i.d.) fat (endogenous CCK) and of CCK infusion on satiety were studied during normo-and hyperglycemic conditions. Eight healthy subjects participated in two protocols consisting of two experiments each. First protocol: (a) normoglycemia (control) with i.d. emulsified fat (i.d. fat) infusion, (b) acute hyperglycemia (HG) with plasma glucose levels stabilized at 15 mmol/L and i.d. fat infusion. In the second protocol the effect of exogenous cholecystokinin (CCK) on satiety was studied during normo- and hyperglycemia. Intraduodenal fat (Intralipid 10%) was infused at a dose of 1 g/h via a nasoduodenal tube in the first protocol, whereas in the second protocol CCK-33 was infused intravenously at a dose of 0.5 IDU/kg x h. Satiety was scored using visual analog scales (VAS). Plasma CCK levels were determined at regular intervals. During infusion of i.d. fat and i.v. CCK the VAS scores of wish to eat, hunger, and prospective feeding decreased significantly (p<0.05) in the normoglycemic experiments. During hyperglycemia satiety did not significantly change in the basal period; however, the scores of wish to eat, hunger, and prospective feeding increased significantly (p<0.05) when i.d. fat or i.v. CCK was administered. Plasma CCK levels in the basal and the stimulated period were not significantly different between normo- and hyperglycemia. In summary, the present study shows that in healthy humans volunteers 1) during normoglycemic conditions satiety can be induced by very low dose of i.d. fat and by CCK infusion, 2) during hyperglycemia the effect of i.d. fat and CCK on satiety are reversed, resulting in increased appetite.