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Biomedical subjects

V L Go

Publications and source records attributed to V L Go.

At least 91 records · Page 5Linked to original sources
PubMed1988

Gastrointestinal and metabolic effects of amylase inhibition in diabetics.

A partially purified amylase inhibitor given with a single meal causes maldigestion of carbohydrate, increases delivery of carbohydrate to the ileum, and reduces postprandial plasma glucose. To determine the effect of more prolonged administration of the inhibitor on gastrointestinal function and carbohydrate tolerance, we studied 6 non-insulin-dependent diabetics (3 previously treated with oral agents and 3 treated with diet alone) for 3 wk while they ate a weight-maintenance diet. Patients taking oral agents continued them during the first week. During the second week, 4-6 g of the inhibitor was given with each meal. Capillary blood glucose concentration was measured before each meal and 90 min postprandially. On the last day of each week venous blood samples for glucose, hormones, and lactic acid analysis and a quantitative stool culture were obtained. Total carbohydrate absorption was estimated by comparing postprandial breath hydrogen on study days 7, 14, and 21 with breath hydrogen after ingesting 15 g of lactulose on days 0, 15, and 22. There 24-h stools were collected and weighed at the end of each week and analyzed for carbohydrate, lactic acid, short-chain fatty acids, pH, dry matter, amylase, and fat. The inhibitor significantly (p less than 0.05) reduced postprandial plasma glucose, C-peptide, insulin, and gastric inhibitory polypeptide concentrations, significantly increased (p less than 0.05) breath hydrogen excretion, and caused carbohydrate malabsorption. Diarrhea occurred the first day the inhibitor was ingested, but thereafter cessation of diarrhea was associated with changes in the metabolism of carbohydrate by colonic flora. As the amylase inhibitor improves carbohydrate homeostasis and is not associated with continuing diarrhea, it may be a useful adjuvant in the treatment of patients with non-insulin-dependent diabetes mellitus.

Aged↗
PubMed1988

Gastrointestinal neuropeptide concentrations following guanethidine sympathectomy.

In an effort to investigate the interaction of the adrenergic and enteric components of the autonomic nervous system, gut neuropeptide concentrations were examined following chemical sympathectomy. Adult male rats were treated with guanethidine (40 mg/kg i.p., 5 days/week for 5 weeks), which selectively destroys peripheral sympathetic neurons. Controls received equal volumes of saline vehicle. Tissues from fundic and pyloric stomach, duodenum, jejunum, jejuno-ileum, ileum, caecum and colon were extracted and concentrations of selected neuropeptides determined by radioimmunoassay. Dopamine-beta-hydroxylase (DBH) in peripheral nerve, measured as an index of degree of sympathectomy, was depleted 80-90%. One week after cessation of treatment, vasoactive intestinal peptide (VIP) was elevated in jejunum (52%), ileum (53%), caecum (41%) and colon (59%), as was neurotensin (NT) in caecum (117%) and colon (261%). Methionine-enkephalin (MET) was lowered in duodenum by 28%. With the exception of MET in duodenum and NT in caecum, these alterations normalized by 5 weeks post-treatment, although DBH remained depressed. Statistically non-significant increases in substance P content were observed in upper gut regions. An inhibitory sympathetic input to VIPergic and NTergic systems is postulated.

Animals↗
PubMed1988

Distribution, quantitation, and origin of immunoreactive neuropeptide Y in the human gastrointestinal tract.

A radioimmunoassay for measurement of immunoreactive neuropeptide Y has been developed using antiserum from a rabbit (221) immunized with porcine neuropeptide Y. Antibody 221 has been characterized for both sensitivity and specificity. To determine the distribution of neuropeptide Y in the human gastrointestinal tract, fresh tissue specimens were separated by microdissection into the muscularis externa and the mucosa-submucosa. To examine the origin of neuropeptide Y in human colon, specimens of aganglionic and ganglionic colon were obtained from patients with Hirschsprung's disease. Immunoreactive neuropeptide Y in human gut was present in highest concentrations in the muscularis externa of the stomach and in lowest concentrations in the muscularis externa of the ileum and descending colon. Neuropeptide Y in the stomach was present in higher concentrations in the muscularis externa than in the mucosa-submucosa, but in the descending colon there were lower concentrations of neuropeptide Y in the muscularis externa than in the mucosa-submucosa. In Hirschsprung's disease, concentrations of neuropeptide Y were increased in aganglionic colon in both the muscularis externa and the mucosa-submucosa, compared to corresponding layers from proximal ganglionic colon. Extracts of the gastric muscularis externa and the colonic mucosa-submucosa were separated by C18 reverse-phase high-performance liquid chromatography. One major immunoreactive species was identified by radioimmunoassay which eluted in a position similar to synthetic human neuropeptide Y. These results demonstrated both regional and layer differences in concentrations of neuropeptide Y in human gut. Increased concentrations of neuropeptide Y in aganglionic colon from Hirschsprung's disease most likely result from enlargement of neuropeptide Y-containing extrinsic nerve fibers in both the mucosa-submucosa and the muscularis externa.

Animals↗
PubMed1988

Potential incretins.

A greater plasma concentration of insulin after isoglycemic enteral than after parenteral administration of glucose is called the incretin effect. The primary mediator of this effect, gastric inhibitory polypeptide, may not account for the complete manifestation of this phenomenon. We evaluated other gastroenteric polypeptides with respect to a differential response to oral ingestion of glucose and intravenous administration of glucose at rates that achieved arterial plasma glucose concentrations matched to those from orally administered glucose. Gastrin, peptide histidine methionine, peptide YY, and neurotensin showed increases in plasma concentrations in response to oral ingestion of glucose but not to intravenous administration of glucose. Vasoactive intestinal polypeptide showed no increased concentration in response to either oral or intravenous administration of glucose. The differential responses to orally and intravenously administered glucose noted in the former gastroenteric polypeptides qualifies them as potential mediators of the incretin effect.

Administration, Oral↗
PubMed1988

Characterization and control of pulsatile secretion of insulin and glucagon.

Periodic oscillation of insulin and glucagon by isolated mice islets has been studied. Pulsatile secretion of insulin and glucagon was observed at all glucose concentrations tested. The frequency of oscillation per 20 min for glucagon was 5.0 +/- 0.26 and for insulin 4.0 +/- 0.26 (n = 6), approximating to periodicities of 4 and 5 min, respectively. These did not change by increasing the glucose concentration to 11.1 or 22.2 mM from 5.5 mM (basal). The maximal amplitude of glucagon secretion was not altered by raising the glucose concentration to 11.1 mM from basal. However, 22.2 mM glucose significantly suppressed the amount of glucagon released when compared with glucagon secretion in the presence of 5.5 mM glucose. In contrast, the maximal amplitude of insulin increased from 444.2 +/- 37.7 to 777.2 +/- 61.4 and from 271.8 +/- 35 to 701 +/- 26.5 pg/min (p less than 0.01, n = 6) by switching from basal to 11.1 and 22.2 mM glucose, respectively. We conclude from this study that the pacemaker controlling pulsatile secretion of insulin and glucagon is within the islet. Although the amplitude of secretion of these hormones is regulated by the ambient glucose concentration, the frequency of their pulsatile secretion is not.

Animals↗
PubMed1988

Opiate antagonist nalmefene inhibits ethanol-induced flushing in Asians: a preliminary study.

Ethanol-induced flushing (EIF) occurs in up to 80% of Asians and is characterized by facial flushing, tachycardia, and increased cardiac output. Since endogenous opiates and prostaglandins may be mediators of flushing syndromes, we attempted to block EIF in four Asian flushers with single doses of either the opiate antagonist nalmefene, or the prostaglandin synthesis inhibitor indomethacin. Nonflushers (2 Caucasian, 2 Asian) and four Asian flushers were given on separate days water, ethanol (0.4 g/kg p.o.), ethanol plus nalmefene (2 mg i.v.), or ethanol plus indomethacin (50 mg p.o.). Ethanol concentrations of flushers and nonflushers were similar. Mean (+/- SEM) plasma acetaldehyde concentrations of flushers (28.2 +/- 11.8 microM) were significantly greater than nonflushers (1.4 +/- 0.5 microM) following ethanol ingestion (p less than 0.001). Ethanol alone always induced a significant rise in facial skin temperature [mean area under the curve (AUC) = 5142 +/- 648 % delta T x min, p less than 0.01] and of pulse (mean AUC = 1622 +/- 120 bpm x min, p less than 0.001) in flushers compared to water ingestion. A single dose of nalmefene (2 mg i.v.) but not indomethacin (50 mg p.o.), reduced the mean (+/- SEM) ethanol-induced rise in facial skin temperature of flushers by 58 +/- 14% (p less than 0.05) without changing plasma acetaldehyde concentrations. These data are preliminary evidence that the opiate antagonist, nalmefene, blocks some of the vascular manifestations of EIF without altering the elevated plasma concentrations of acetaldehyde.

Acetaldehyde↗
PubMed1988

Role of gastric inhibitory polypeptide in postprandial hyperinsulinemia of obesity.

To assess the contribution of gastric inhibitory polypeptide (GIP) to the postprandial hyperinsulinemia of obesity, secretion rates of GIP (generated from kinetic analyses from infusions of porcine GIP) and insulin (from C-peptide applied to a validated kinetic model) to meals of 3 sizes were determined in 10 obese (5 male and 5 female) and 10 lean, sex- and age-matched healthy subjects. Although the postprandial secretion rates of GIP were greater in obese subjects (P = 0.03), postprandial concentrations of GIP were not. The latter may be explained by the greater volume of distribution of GIP in obese subjects (P = 0.036). Secretion rates and volume of distribution of GIP were correlated (r = 0.652, P less than 0.01). Despite excessive integrated postprandial (P = 0.010) insulin concentrations, insulin secretion was not significantly different between obese and lean subjects. We conclude that 1) although postprandial plasma GIP concentrations are normal, GIP secretion is increased in obesity, 2) the postprandial hyperinsulinemia of obesity is not due to excessive insulin secretion but is likely secondary to altered insulin clearance, and 3) GIP cannot account for the hyperinsulinemia of obesity through its insulinotropic action.

Adult↗
PubMed1988

Human pancreatic secretion during phase II antral motility of the interdigestive cycle.

We determined if changes in the irregular motor activity of phase II, the dominant motility phase in awake fasting humans, are associated with fluctuations in pancreatic secretion by intubating the upper gastrointestinal tract of 15 healthy humans and recording antral and duodenal motility and obtaining duodenal samples for one or two interdigestive motility cycles. Antral phase II activity was graded as having low, intermediate, or high frequency of contractions and related to duodenal trypsin output and plasma concentrations of motilin and human pancreatic polypeptide (HPP), a marker of vagal cholinergic tone. Low, intermediate, and high phase II motor activities were significantly associated with trypsin outputs (U/10 min; mean +/- SE) of 576 +/- 137, 1,441 +/- 225, and 3,621 +/- 521, respectively (P less than 0.001). Plasma motilin levels did not vary with the grades of phase II motility (P greater than 0.1), but levels of plasma HPP and the grades of phase II motility were positively correlated (P less than 0.001). The close correlation among motility, pancreatic secretion, and plasma HPP during phase II suggests that vagal cholinergic pathways are involved in the common regulatory mechanism controlling phase II interdigestive motility and pancreatic secretion.

Adolescent↗
PubMed1988

Incretin effect due to increased secretion and decreased clearance of insulin in normal humans.

To assess the contribution of changes in insulin secretion and clearance to the incretin effect (greater insulinemia after oral than after intravenous glucose), 10 healthy subjects were studied after oral glucose (1 g/kg body wt) and again when glucose was infused intravenously at rates to match arterialized plasma glucose concentrations after oral glucose. Although basal and integrated plasma glucose did not differ between oral and intravenous glucose, integrated responses of insulin (3.3 +/- 0.5 vs. 1.8 +/- 0.4 mU ml-1.240 min-1, P less than .001), C-peptide (456.5 +/- 58.5 vs. 327.9 +/- 46.3 ng.ml-1.240 min-1, P = .002), gastric inhibitory polypeptide, (16.8 +/- 3.5 vs. -2.8 +/- 1.0 micrograms.ml-1.240 min-1, P less than .001), and insulin secretion (6.6 +/- 1.1 vs. 4.7 +/- 0.7 U.240 min-1, P = .003) were greater with oral than intravenous glucose. However, insulin clearance, whether calculated as the molar ratio of integrated C-peptide to integrated insulin responses (6.9 +/- 0.7 vs. 14.2 +/- 3.8, P = .005) or from the formula insulin clearance equals insulin secretion divided by integrated insulin responses (1.1 +/- 0.2 vs. 2.5 +/- 0.7 L.min-1.m-2, respectively, P = .002), was less for oral than for intravenous glucose. Therefore, the incretin effect is mediated both by increased secretion and decreased clearance of insulin.

Administration, Oral↗
PubMed1988

Subnormal pancreatic polypeptide and epinephrine responses to insulin-induced hypoglycemia identify patients with insulin-dependent diabetes mellitus predisposed to develop overt autonomic neuropathy.

Sixteen patients with insulin-dependent diabetes mellitus with no current evidence of autonomic dysfunction underwent an insulin tolerance test during which plasma pancreatic polypeptide and epinephrine responses were determined. Compared to 11 age- and weight-matched nondiabetic volunteers, 9 diabetic subjects had subnormal plasma pancreatic polypeptide responses (n = 6) or plasma epinephrine responses (n - 8). When autonomic function was reassessed 2 to 3 years later by standard cardiovascular reflex tests and clinical examination, 8 of 9 diabetic subjects with subnormal hormonal responses to hypoglycemia developed either abnormal cardiovascular reflexes (6 of 9) or overt symptoms consistent with diabetic autonomic neuropathy (6 of 9), whereas none of the subjects with previously normal plasma pancreatic polypeptide and epinephrine responses did (P less than 0.01). Diminished pancreatic polypeptide and epinephrine responses to hypoglycemia can predict the development of overt autonomic neuropathy in patients with insulin-dependent diabetes mellitus; identification of patients with a predilection to develop autonomic neuropathy may permit earlier treatment.

Adult↗
PubMed1987

Neuronal cholecystokinin-like immunoreactivity is postprandially released from primate hypothalamus.

By use of the push-pull perfusion technique, release of neuronal cholecystokinin-like immunoreactivity (CCK-LI) from hypothalamus of owl monkeys was investigated in relation to an intragastric meal. In overnight fasted, halothane-anesthetized owl monkeys, levels of CCK-LI in the hypothalamic push-pull perfusate were below assay sensitivity (less than 4 pg/30 min). After intragastric administration of a carbohydrate/amino acid meal, however, a 10-fold increase in CCK-LI release (51 +/- 7 pg/30 min) was observed in 5 out of 15 perfusion sites during the first postprandial 30 min. During the subsequent two 30-min intervals, release of CCK-LI was still increased with 32 +/- 5 pg/30 min and 15 +/- 6 pg/30 min, respectively. Thereafter, CCK-LI release was below assay sensitivity again. Addition of 40 mM potassium chloride (KCl) to the perfusion solution, which causes neuronal depolarization, resulted in a second increase in CCK-LI release of 56 +/- 7 pg/30 min which was comparable to the meal-induced release. All sites that exhibited an increase in CCK-LI were located in the anterolateral aspect of the hypothalamus. In experiments without meal-induced release, KCl did not have any effect on CCK-LI in perfusate, suggesting that these particular sites did not contain CCK-releasing terminals. High performance liquid chromatography (HPLC) identified the C-terminal octapeptide of CCK (CCK-8) as the predominant molecular form of CCK within the owl monkey hypothalamus. No gastrin-17 was present.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Identification and distribution of immunoreactive peptide YY in the human, canine, and murine gastrointestinal tracts: species-related antibody recognition differences.

A radioimmunoassay using two antisera (antibody 80 and antibody 213) from rabbits immunized with porcine peptide YY has been characterized for both sensitivity and specificity. To determine the distribution of peptide YY in the gut, fresh tissue specimens from the human and canine gut were separated into mucosal-submucosal and muscularis externa layers by microdissection. These tissues and transmural specimens from murine gut were acid-extracted and neutralized, followed by radioimmunoassay using each antiserum. Immunoreactive peptide YY in canine and murine gut was present in similar concentration and distribution using each antiserum, with highest concentrations in the mucosal-submucosal layer of the descending colon. Using antibody 213, immunoreactive peptide YY throughout the human gut was measured only at the lower detection limit of the radioimmunoassay. By contrast, using antibody 80, peptide YY in human gut was present in a distribution similar to canine and murine gut. Using antibody 80, one major immunoreactive species was identified with C18 reverse-phase high-performance liquid chromatography in extracts of human, canine, and murine colon. These results suggest species-related antibody recognition differences. The similar concentrations of peptide YY in canine and murine gut determined with the two antisera are consistent with the hypothesis that the amino acid sequences of canine and murine peptide YY are similar to porcine peptide YY. Using antibody 213, the low concentrations of immunoreactive peptide YY found in human gut are consistent with the hypothesis that human and porcine peptide YY have different amino acid sequences. Antisera prepared by immunization with porcine PYY must therefore be carefully characterized prior to studies using human sera or human tissue extracts.

Animals↗
PubMed1987

Release of cholecystokinin from rat cerebral cortex in vivo: role of GABA and glutamate receptor systems.

Using cortical cups in chloralose-urethanized rats, the in vivo release of cholecystokinin-like immunoreactivity (CCK-LI) from cerebral cortex was examined. Resting levels of cholecystokinin-like immunoreactivity ranged from 20 to 30 pg/20 min sample. The addition of potassium (40 mM) in excess, resulted in a highly significant elevation in the levels of CCK-LI in the cortical superfusate. Deletion of calcium and the substitution of cobalt (10 mM), resulted in a significant reduction in both resting release and the release otherwise evoked by the addition of potassium. Focal electrical stimulation of the cortex (20 Hz), resulted in a significant (1.9 +/- 0.2-fold, n = 8) increase in the levels of CCK-LI. The addition of glutamate (10(-6)-10(-4) M) of kainic acid (10(-8)-10(-6) M), also resulted in significant elevations in the levels of CCK-LI. The co-administration of a putative glutamate receptor antagonist, kynurenic acid (10(-4) M) resulted in a significant reduction in the levels of release otherwise evoked by the addition of glutamate, but not by electrical stimulation. The addition of GABA (10(-5)-10(-3) M) resulted in a dose-dependent decrease in the resting release of CCK-LI, and the release evoked by glutamate. Picrotoxin (10(-6)-10(-4) M), resulted in a highly significant increase in the levels of CCK-LI in the cortical effluent. These results are consistent with a tonic GABAergic inhibition of CCK-releasing neurons. The treatment of the animal with diazepam (30 mg/kg, i.p.) also resulted in a significant reduction in resting release and the release otherwise evoked by focal cortical stimulation.

Amino Acids↗
PubMed1987

Distribution and quantitation of gut neuropeptides in normal intestine and inflammatory bowel diseases.

To study hyperplasia of peptidergic nerves purported to be diagnostic of Crohn's disease, we determined the distribution and concentrations of gut neuropeptides in specimens of normal intestine, ulcerative colitis, and Crohn's disease. Tissue specimens obtained at surgery were dissected into the mucosal-submucosal and muscularis externa layers, and immunoreactive gut neuropeptides were acid-extracted for measurement by radioimmunoassay. The immunoreactive species were characterized by column chromatography. Mucosal-submucosal layer concentrations of vasoactive intestinal peptide were significantly decreased in Crohn's colitis and ulcerative colitis, while mucosal-submucosal layer concentrations of substance P were significantly increased in left-sided ulcerative colitis. Muscularis externa layer concentrations of vasoactive intestinal peptide and met5-enkephalin were decreased in left-sided Crohn's colitis. These neuropeptide concentration abnormalities did not clearly differentiate between Crohn's colitis and ulcerative colitis, and no increase in concentration of a neuropeptide diagnostic of Crohn's disease was identified.

Adult↗