Autonomic and endocrine participation in opioid peptide-induced hyperglycemia.

Intracisternal administration of synthetic human beta-endorphin to conscious, ambulatory adult male rats caused dose-related increases in plasma glucose concentration. The largest dose of beta-endorphin examined, 7.25 nmol, increased plasma glucose concentration within 7 min and this effect lasted 2.5 h. On the other hand, only 58 pmol was required to induce transient hyperglycemia, when compared to the response observed in saline-injected control rats. This hyperglycemic effect of beta-endorphin was prevented by prior systemic administration of naloxone, thus supporting the hypothesis that this beta-endorphin-induced effect is mediated at opioid receptors. beta-Endorphin also markedly increased plasma concentrations of epinephrine, norepinephrine and, to a lesser extent, dopamine. A significant positive correlation was demonstrated between plasma glucose and plasma epinephrine responses to increasing doses of intracisternally administered beta-endorphin. In addition, intracisternal beta-endorphin also increased plasma glucagon concentration without significantly increasing plasma insulin concentration. Thus, it is probable that epinephrine and glucagon are the major factors mediating this hyperglycemic effect. beta-Endorphin-induced hyperglycemia was prevented by ganglionic blockade with chlorisondamine. This further supports the thesis that intracerebral beta-endorphin increases plasma glucose concentration by activation of the central autonomic outflow. In addition to these effects on short-term regulators of glycemia, intracisternal beta-endorphin increased plasma concentrations of corticosterone and growth hormone. Both of these glucose counterregulatory hormones may play minor roles in modulating beta-endorphin-induced hyperglycemia.

Motilin and human pancreatic polypeptide measured in CSF from alcoholic and non-alcoholic neurological patients.

Thirty-one CSF samples from alcoholics and non-alcoholic neurological patients were assayed for immunoreactive motilin and human pancreatic polypeptide (HPP). Both peptides were detected in all samples. Alcoholics without liver disease had significantly higher levels of motilin and lower levels of HPP than neurological controls.

Radioimmunoassay of c-myc protein.

A sensitive radioimmunoassay for human c-myc protein was developed by using an amino-terminal fragment of c-myc protein, c-myc(11-24). Immunoreactive c-myc protein was found to be present in 3 human tumors (HL-60, N231, Lu-65), which are known to have c-myc gene amplification. In contrast, c-myc protein was undetectable in 1 human tumor (H69) without c-myc gene amplification as well as in human heart tissues.

PHI structural requirements for potentiation of glucose-induced insulin release.

Immunoreactive PHI was detected in rat pancreas. The potentiating effect of 10(-9) M PHI upon insulin release from the isolated perfused rat pancreas was significant and most consistent when 250 mg% glucose was present in the perfusion medium. PHI(1-15) retained a substantial potentiating effect on insulin release, while PHI(14-27) was essentially inactive. Replacement of amino-terminal decapeptide portion of the PHI molecule with the corresponding part of VIP resulted in a drastic decrease of the potentiating effect of PHI on insulin release. 10(-8) M PHI(14-27) substantially diminished the potentiation by 10(-9) M PHI while PHI(1-15) was without an inhibitory effect. The present results indicate that the PHI active site for potentiation of glucose-induced insulin release resides in the amino-terminal segment of the molecule but requires the carboxyl terminal segment primarily for binding to exhibit full biological activity.

Diabetic Chinese hamsters: metabolic effects of long term guar gum consumption.

The effect of 13 weeks of guar gum or cellulose diet consumption upon metabolic parameters was examined in diabetic and control adult Chinese hamsters. Diabetic hamsters displayed typical diabetic metabolic profiles. Both 8% guar gum and 8% cellulose diets maintained body weights in all 4 groups during the study. Diabetic and control hamsters fed guar gum drank less water as the study progressed. At weeks 9 and 13, diabetic hamsters fed guar gum excreted less urine compared to those fed cellulose. Diabetic hamsters fed guar gum had reduced urinary glucose excretion at weeks 1, 9 and 13 compared to those fed cellulose. Control hamsters fed either diet had normal urine volumes with only traces of glucose. Similar fasting plasma glucose levels were measured initially for all diabetic hamsters; all 3 subsequent measurements revealed lower levels for the group fed guar gum. Control hamsters had normal fasting plasma glucose levels. Comparable fasting plasma insulin levels were measured for all diabetic hamsters; these levels increased during the study. Control hamster fasting plasma insulin levels were 3 times higher and did not change. Throughout the study, diabetic hamsters fed guar gum consistently had healthier metabolic profiles than those fed cellulose.

Guar gum consumption in adolescent and adult rats: short- and long-term metabolic effects.

Metabolic responses to short- and long-term guar gum consumption were studied in adolescent and adult rats. For the long-term study, male adolescent rats were divided into four groups (n = 60/group) and fed guar gum, cellulose, or bran diet for 67 weeks. Metabolic studies (food--water intake, feces--urine output, body weight, carbohydrate tolerance) were performed eight times during the 67 weeks. The guar gum group consumed less diet throughout the entire study and gained less weight over the first 20 weeks compared with the cellulose and bran groups. A second bran-fed group was food restricted over the first 20 weeks to match the reduced weight gain of the guar gum group and then fed ad libitum. Reduced plasma glucose excursions were measured for only the guar gum group after both fibre-free glucose and sucrose challenges at weeks 6, 12, and 18; from 24 to 64 weeks all four groups had similar glucose tolerance responses. Twenty-four hour urinary glucose excretion was similar during all eight metabolic studies up to 64 weeks for guar gum and cellulose groups. In the short-term study, male adolescent (200 g; n = 10/group) and adult (630 g; n = 15/group) rats were divided into five and four groups, respectively, and fed guar gum, guar by-product (GBP), cellulose, or bran diet for 6 weeks. A metabolic study was performed during the 6th week. Adolescent rats fed guar gum or GBP diets gained less weight than the cellulose group; only the guar gum group displayed improved carbohydrate tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Guar by-product improves carbohydrate tolerance in healthy human subjects.

Guar gum possesses distinct hypoglycemic properties. The other fraction of the guar bean, guar by-product (GBP), was studied to determine if it possesses any hypoglycemic properties. When 25 g GBP or wheat bran were consumed with a carbohydrate test meal by 10 healthy subjects, at 15 and 30 min after the GBP test meal significantly lower normalized plasma glucose responses were measured. Postprandial plasma insulin responses were similar after both test meals. During the first 60 min postprandially, the mean integrated plasma glucose response area was significantly lower after the GBP test meal. These data indicate that GBP, like guar gum, possesses hypoglycemic properties; because of the different chemical characteristics of these 2 guar bean fractions, it seems that their hypoglycemic properties are due probably to different mechanisms.

Guar by-product improves carbohydrate tolerance in rats.

These studies were designed to assess the effect of guar by-product (GBP) upon carbohydrate tolerance in rats. Both 1% and 10% GBP suspensions administered immediately before a glucose challenge (1 g/kg body weight) caused a 31% reduction in the integrated plasma glucose response area during a 180 min test. Because 10% GBP caused a flattened glucose response curve, it was studied further. Ten percent GBP caused a similar reduction in plasma glucose during a 360-minute test; similar plasma insulin levels were measured in both 0% and 10% GBP groups throughout the 360-minute test. Ten percent oat bran and 10% soy bran had no effect upon plasma glucose responses. Ten percent GBP was effective in lowering glycemic excursions after sucrose and starch challenges. Rats fed pellet fractions from water and acid treated GBP had the lowest plasma glucose excursions after a glucose challenge; simulated gastric juice treatment of GBP reduced the hypoglycemic activity and simulated pancreatic juice treatment destroyed it. These studies demonstrate the ability of GBP suspensions to significantly reduce plasma glucose excursions after carbohydrate challenge.

Plasma glucose and insulin responses in growing rats fed a total parenteral nutrition diet either intravenously or intragastrically.

The effect of administering either intravenously (group I) or intragastrically (group II) a glucose-amino acid total parenteral nutrition diet over a 12-day period upon plasma glucose and insulin responses was examined in adolescent rats. Infusion of the 25% glucose - 12.2% amino acid diet at a rate of 300 kCal X kg body weight-1 X 24 h-1 supported normal weight gain over the 12-day study period in both intravenously (group I) and intragastrically (group II) alimented rats. Mean plasma glucose levels rose dramatically in both groups by the end of day 1; group I had significantly higher mean plasma insulin levels. By day 3, the group I mean plasma glucose value decreased significantly while the group II mean glucose value remained virtually unchanged. Mean plasma insulin values more than doubled in both groups with the group I level still remaining significantly above the group II level. At days 6 and 12, group I mean plasma glucose levels were significantly below group II while both groups had similar plasma insulin levels. Data from this 12-day intravenous-intragastric alimentation study reveals quite different metabolic responses compared with acute (120-180 min) studies of the enteroinsular axis.

Prostaglandin biosynthesis by gastric mucosa. I. Studies in rat.

A technique for determination of the prostaglandin E2 biosynthetic capacity ( PGBC ) of gastric mucosa is described. The effects of food deprivation and indomethacin pretreatment on PGBC were studied. Indomethacin (1 mg/kg i.p.) significantly reduced the PGBC of fundal and antral tissue. This effect was more marked in the fundal tissue. Food deprivation for up to 22 h had no effect on fundal PGBC . In the antrum, a 12-hour fast caused a significant reduction in PGBC while a 22-hour fast had no effect. These changes in PGBC may relate to the increase in susceptibility to gastric ulceration caused by fasting or indomethacin pretreatment. This technique may be applicable to clinical studies.

Cholinergic control mechanisms for immunoreactive motilin release and motility in the canine duodenum.

The relationship of immunoreactive (IR) motilin release from the duodenum to duodenal motility changes was investigated in anaesthetized dogs. Stimulation of one or both vagi at 5 or 15 Hz or field stimulation of intrinsic duodenal nerves produced significant increases in duodenal vein IR motilin concentrations and accompanying increases in duodenal motility. However, only stimulation of both vagi at 15 Hz produced significant changes in peripheral venous concentrations of IR motilin. These occurred after a delay at a time when both the duodenum and the antrum were quiescent. Either hexamethonium or atropine blocked IR motilin release induced by stimulation of intrinsic or extrinsic nerves while only atropine inhibited the release induced by intraarterial carbachol. The response stimulated by carbachol and blocked by atropine was tetrodotoxin insensitive and the muscarinic receptor involved was presumably located on a nonneural structure. The site sensitive to hexamethonium was presumably the neural pathway which terminated at the muscarinic receptor. Concomitant studies of duodenal motility responses to vagal and field stimulation suggested a conventional neural pathway with preganglionic cholinergic nerves in the vagus, postganglionic cholinergic nerves in the duodenum (activated by field stimulation) and a smooth muscle muscarinic receptor. Activation of antral motility by stimulation of the abdominal vagus or intraarterial carbachol injections to the antrum increased duodenal IR motilin release in the absence of duodenal motility. Thus activation of the intrinsic nerves which cross the pylorus initiated IR motilin release as well as inhibited duodenal motility.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic mild restraint protects the rat gastric mucosa from injury by ethanol or cold restraint.

The effects of chronic mild restraint on the susceptibility of the rat gastric mucosa to ethanol or cold-restraint injury were studied. Gastric mucosas of animals subjected to chronic mild restraint exhibited less damage when bathed with 40% ethanol than those of control animals. This reduced damage was observed with 2 days of mild restraint and was maximal (93% less damage; p less than 0.0005) when the animal was mildly restrained for 10 days. Pretreatment with indomethacin abolished the protection afforded by chronic mild restraint, suggesting a mechanism involving endogenous prostaglandin synthesis. Chronic mild restraint significantly (p less than 0.05) reduced the injury to the gastric mucosa caused by cold-restraint stress. This model of mild restraint may prove useful in future studies on the mechanism of stress-induced and other gastric mucosal lesions.

Regulatory peptides of the gut and brain.

The concept of the gut-brain axis has emerged from the recent demonstration, mainly by radioimmunoassay and immunohistochemistry, that many peptides are common to both gut and brain cells. The general term regulatory peptide is at present the most appropriate for these peptides until more is known about their precise hormonal, neurotransmitter and neuromodulator activities. Consideration of possible local endocrine (paracrine) and neuroendocrine secretion necessitates re-evaluation of the importance of peripheral regulatory peptide concentrations. Central and peripheral administration of these peptides is a useful way to establish their potential regulatory roles in endocrine and nervous pathways. The concept of the gut-brain axis demonstrates the intimate relations between endocrinology and neuroendocrinology.

Sustained pectin ingestion delays gastric emptying.

The effects of sustained fiber ingestion on gastric emptying glucose tolerance, hormone responses, and jejunal absorption of glucose and lysine were studied in healthy volunteers. Subjects were placed on a low-fiber (3 g) diet for 2 wk, followed by 4 wk of an isocaloric diet supplemented with 20 g/day of either apple pectin (7 subjects) or alpha-cellulose (6 subjects). At the conclusion of each dietary period subjects ingested a low-fiber breakfast surface-labeled with 99mtechnetium sulfur-colloid. Gastric emptying half-time, plasma glucose, calcium, phosphorus, insulin, glucagon, gastrin, human pancreatic polypeptide, and motilin were determined. Gastric emptying half-time was prolonged approximately twofold after pectin supplementation (p less than 0.005) and returned to normal 3 wk after discontinuing pectin supplementation. Cellulose supplementation did not alter the gastric emptying rate. Plasma glucose, calcium, phosphorus, and hormonal responses to the meal were unchanged after either pectin or cellulose supplementation. Pectin ingestion did not impair intestinal absorption of glucose or lysine. In contrast to sustained cellulose ingestion, sustained pectin ingestion slows the gastric emptying rate; the mechanism underlying this adaptive effect is unknown.

Cholinergic control of canine antral immunoreactive gastrin release and motility.

We used acute anesthetized dogs to investigate the role of cholinergic receptors in the relationship between antral immunoreactive (I) gastrin release and antral motility. Electrical stimulation of extrinsic nerves via the cervical vagus or the nerve of Latarjet appeared to increase I gastrin release and antral motility by separate pathways as blockade of muscarinic receptors, i.e., atropinization inhibited motility but did not alter I gastrin release. On the other hand, blockade of nicotinic receptors by hexamethonium treatment obliterated I gastrin release induced by stimulation of the extrinsic nerves but only reduced motility. Field stimulation of intrinsic nerves via serosal electrodes also increased both I gastrin release and local motility. Since hexamethonium treatment only slightly reduced both I gastrin release and motility and atropinization eliminated both during field stimulation, the presence of a muscarinic receptor in the final pathway for each is proposed. Atropine eliminated carbachol-induced I gastrin release and motility increases, even in the presence of nerve blockade by tetrodotoxin. This suggests that this muscarinic receptor is on the smooth muscle cell itself and possibly on the gastrin cell. However a proposed role of the somatostatin cell in controlling gastrin release is also consistent with these data. Thus, both an intrinsic cholinergic and a separate extrinsic noncholinergic pathway are involved in antral release of I gastrin but initiation of motility appears to involve a final common pathway terminating in a muscarinic receptor on the smooth muscle cell.

Improved carbohydrate tolerance in fibre-fed rats: studies of the chronic effect.

The effect of chronic consumption of diets containing either different sources of dietary fibre (8% guar, 8% pectin, or 8% multifibre) or low carbohydrate upon carbohydrate tolerance was examined in rats. Weight gain was significantly lower throughout the entire 28-day study period with the guar group and after 20 days with the multifibre group. When tested with a liquid meal (1 g sucrose/kg body weight) after 14 days on the diets, only the guar rats had significantly lower fasting and postprandial plasma glucose concentrations. After 28 days, the improved carbohydrate tolerance persisted in the guar rats and started to appear in the multifibre rats. Pectin and low carbohydrate diets had no effect upon either weight gain or carbohydrate tolerance. Consuming the fibre diets did not affect jejunal sucrase activities. Jejunal glucose uptake activity was significantly diminished when measured in fasting guar rats while postprandially activities were similar to controls. Jejunal Na-K-ATPase activities in fasting and postprandial guar rats were not related to changes in glucose uptake. These studies confirm that only certain types of dietary fibre improve carbohydrate tolerance and suggest that reduced weight gain and altered intestinal glucose uptake are factors involved in the chronic fibre effect.

Bombesin-like immunoreactivity in developing human lung.

Bombesin-like immunoreactivity (BLI) was detected by a specific radioimmunoassay in extracts of 15 human lungs from fetuses, neonates, infants and children. A higher concentration of lung BLI was found in the fetal/neonatal group (2053.2 +/- 316.3 ng bombesin/g protein, n = 6) compared to the infant/children group (416.3 +/- 64.3 ng/g, n = 9). The peaking of BLI in lungs during the fetal/neonatal period suggests an important function for this peptide in intrauterine life and neonatal adaptation.