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Biomedical subjects

V Harris

Publications and source records attributed to V Harris.

At least 55 records · Page 3Linked to original sources
PubMed1982

Role of H2-receptors in gastrogenic hyperglycemia and hyperinsulinemia in dogs.

Recent studies have demonstrated that an acidified liver meal stimulates insulin release and raises plasma glucose levels. To examine the mechanism of these changes, a liver extract test meal at either pH 7 or at pH 2 was instilled into the stomach of dogs with a bisected pylorus and a gastric fistula during the infusion of either cimetidine, a specific H2-receptor antagonist, or a saline control. In response to the meal at pH 2 insulin, glucagon and glucose levels rose significantly and were not significantly changed by the infusion of cimetidine. In response to the liver meal at pH 7 a late rise in plasma glucagon levels was observed while plasma insulin and glucose did not change significantly; however, during the infusion of cimetidine a significant rise in plasma insulin and glucose levels occurred. The present data suggest that H2-receptors participate in an inhibitory mechanism with respect to the insulin and glucose response during the gastric phase of a neutral meal, but they do not seem to be involved in the rise in insulin and glucose observed in response to an acidified gastric meal.

Animals↗
PubMed1982

Kassinin: stimulation of insulin and glucagon secretion in the rat.

The effect of the newly discovered tachykinin dodecapeptide kassinin on endocrine pancreatic function was examined in the rat and compared to that of substance P, a neuropeptide which is structurally closely related to kassinin. Kassinin, injected iv in graded doses 10, 20, and 30 min before blood collection, significantly increased both plasma insulin and plasma glucagon in a dose-related fashion. The largest dose examined (10 micrograms) increased plasma insulin by 275% and plasma glucagon by 77%. In contrast, iv injections of equimolar doses of substance P did not affect either hormone. However, both kassinin and substance P increased plasma glucose levels in a dose-dependent fashion. Kassinin appears to have biological actions on the endocrine pancreas which clearly can be distinguished from those of substance P. Should kassinin be present in mammalian tissue and show a distribution similar to that of other neuropeptides, it may play a role in the physiological regulation of carbohydrate metabolism.

Animals↗
PubMed1982

Extraction of somatostatin from human plasma on octadecylsilyl silica.

Human plasma contains substances that interfere with the radioimmunoassay (RIA) of somatostatin-like immunoreactivity (SLI). A method has been developed for rapid, reproducible extraction of somatostatin from human plasma on octadecylsilylsilica (ODS). Hydrophobic binding of somatostatin to ODS permitted extraction of the peptide from untreated human plasma, elution of less tightly bound substances with dilute acid, and then elution of somatostatin by 80:20 acetonitrile:0.1% trifluoroacetic acid. The lyophilized extract was reconstituted to a volume of 0.5 ml prior to quantification by RIA. This 6-fold concentration resulted in an effective lower limit of detection of 7.5 pg/ml of plasma. The interassay coefficient of variation for the combined extraction and RIA was 20% (n = 10) at a mean plasma level of 15 pg/ml. Basal concentrations of somatostatin in human plasma ranged from 8 to 20 pg/ml (n = 35, mean - 13.3 +/- 0.4). Basal somatostatin levels (mean = 14.0 +/- 0.4 pg/ml) for nonobese (BMI less than 30, n = 10) were not different from values (mean = 13.3 +/- 0.7 pg/ml) observed for the obese group (BMI greater than 35, n = 17) nor from the values (n = 8, x = 15.4 +/- 1.2 pg/ml) obtained for subjects with non-insulin dependent diabetes mellitus.

Adolescent↗
PubMed1981

Role of histamine H2-receptors in gastric and pancreatic release of somatostatin-like immunoreactivity during the gastric phase of meal.

The present study was designed to determine the role of H2-receptors in the postprandial release of somatostatin-like immunoreactivity (SLI) from the gastric fundus and antrum and from the pancreas. In dogs subjected to laparotomy, the pylorus was bisected and a gastric fistula was created, following which 250 ml 20% liver extract (LE) at pH 7 or 2 were instilled intragastrically. In the fundic vein the incremental SLI rise in response to LE at pH 7 was 2423 plus or minus 540 pg/ml during a control infusion of saline and 4780 plus or minus 863 pg/ml during the infusion of cimetidine (1 mg/kg per h) (P less than 0.05). In the antral vein the incremental SLI in response to LE at pH 7 was 2182 plus or minus 530 pg/ml during the saline control but did not rise significantly during cimetidine infusion. In the pancreatic vein the incremental SLI level after LE at pH 7 was 1953 plus or minus 358 pg/ml in the control experiments and 4430 plus or minus 1024 pg/ml during cimetidine infusion (P less than 0.025). The incremental inferior vena cava SLI level was approximately 925 pg/ml in both groups (not significant). The instillation of LE at pH 2 during the saline control lowered fundic vein SLI by 500 pg/ml; this decline was abolished during cimetidine infusion. In the antral vein the incremental SLI level of 15 750 plus or minus 2514 pg/ml during saline was lowered to only 6728 plus or minus 2257 pg/ml during cimetidine (P less than 0.025). After LE at pH 2 the incremental pancreatic vein SLI level of 5641 plus or minus 1175 pg/ml during the control infusion was also significantly reduced to 2392 plus or minus 559 pg/ml by cimetidine (P less than 0.05). The incremental SLI in the inferior vena cava was reduced from 1270 plus or minus 280 pg/ml during saline to 680 plus or minus 190 pg/ml when cimetidine was infused (P less than 0.05). The present data suggest a histaminergic influence via stimulation of H2-receptors upon the regulation of gastric and pancreatic somatostatin release during the gastric phase of a meal.

Animals↗
PubMed1981

Kassinin and substance P stimulate somatostatin release in the rat.

1. The effect of the tachykinin dodecapeptide kassinin, which has been extracted from the skin of several African frogs, on somatostatin release was examined in the rat and compared with that of the neuropeptide substance P. 2. Equimolar doses of the two peptides were injected intravenously and the animal killed at specified intervals after injection. Somatostatin was measured by a specific radioimmunoassay. 3. Kassinin and substance P had no effect when given in low doses (0 . 1 and 1 . 0 microgram). However, when administered in a dose of 10 . 0 microgram, both peptides significantly increased plasma somatostatin, by 31 and 22% respectively. 4. These findings suggest that kassinin and substance P have common endocrine actions. The effect of somatostatin release may be specific for tachykinins, since other neuropeptides such as the enkephalins have no effect.

Animals↗
PubMed1981

Progressive bony dysplasia in Apert syndrome.

Ten patients with Apert syndrome (type I acrocephalosyndactyly) were studied. Seven of these patients were observed from infancy for periods ranging from 2 1/2 to 22 years. The patients presented with limited joint mobility and were found to have multiple radiographic abnormalities, including subluxated or flattened humeral heads, irregularities of the glenoid cavity, and early fusion of the calcaneus to the cuboid bone. The limitation of motion and bony defects were progressive, suggesting that Apert syndrome is a generalized dysplasia.

Acrocephalosyndactylia↗
PubMed1981

Plasma somatostatin-like immunoreactivity during the interdigestive period in the dog.

To study possible physiologic relationships between somatostatin and the gastric interdigestive contractions (GIC), gastric motor activity, and plasma somatostatin-like immunoreactivity (SLI) concentration were determined simultaneously in four conscious dogs, each of which was studied on two separate occasions. Plasma SLI level was highest during the GIC period and lowest 60 and 80 min after the cessation of the GIC; the mean difference in plasma SLI was 41 +/- 6 pg/ml. When synthetic motilin, a known stimulus of GIC, was infused at a physiologic rate during the period in which plasma SLI levels were low, SLI rose to approximately the same values observed during the contraction period and GIC similar to those that occur spontaneously were observed. When synthetic somatostatin, a known inhibitor of endogenous motilin release, was infused at a rate that raised the plasma SLI to approximately the levels observed during the contraction period (0.1 microgram/kg per h), the appearance of the subsequent GIC was significantly delayed. These results are consistent with a physiological role for somatostatin in the regulation of GIC in dogs and suggest an interrelationship between motilin and somatostatin.

Animals↗
PubMed1981

Effect of gastric inhibitory polypeptide on plasma levels of chylomicron triglycerides in dogs.

To determine whether gastric inhibitory polypeptide (GIP) promotes the clearance of chylomicron triglycerides (TG) from the circulation in dogs, chyle collected from donor dogs via a thoracic duct fistula was infused at a rate of 2 ml/min i.v. into normal recipient dogs during an infusion of either porcine GIP (1 microgram/kg per h) or saline as a control. In the GIP-infused dogs the rise in plasma TG was significantly below that of the control animals [mean peak of 36 +/- 4 mg/dl vs. 82 +/- 18 mg/dl (P less than 0.05)]. It is concluded that GIP exerts an effect upon the removal of chylomicron TG from the blood. The results suggest that GIP may play a physiologic role in the disposition of ingested fat.

Animals↗
PubMed1981

Effect of 2-deoxy-D-glucose on plasma somatostatin levels in conscious dogs.

The effects of 2-deoxy-D-glucose (2-DG) on plasma levels of somatostatin-like immunoreactivity (SLI) were examined in conscious normal dogs. After an iv infusion of 2-DG (400 mg/kg . h for 15 min), plasma SLI rose significantly from a mean baseline of 130 +/- 5 pg/ml (mean +/- SEM) to a mean peak of 204 +/- 25 pg/ml (P less than 0.005) at 25 min. Plasma insulin and glucagon also increased significantly. Atropine (200 microgram/kg . h for 35 min, iv) and hexamethonium (5 mg/kg, iv) markedly suppressed the SLI response to 2-DG, suggesting that it might be mediated, at least in part, by the autonomic nervous system. In contrast, the plasma insulin and plasma glucagon responses to this glucose analog were only slightly affected by atropine or hexamethonium pretreatment. Carbachol (0.2 mg, sc) caused a mean maximal increase in SLI of 43 +/- 14% (P less than 0.005) and atropine (200 micrograms/kg . h, iv) caused a mean maximal decrease of 25 +/- 2% (P less than 0.001) from the respective baseline levels. Plasma insulin and glucagon rose promptly after carbachol and were unchanged by atropine. To assess th contribution of 2-DG-stimulated gastric acid secretion in the 2-DG-induced SLI rise 2-DG was infused during the infusion of the H2-receptor antagonist cimetidine (3.0 mg/kg . h). Plasma SLI, nevertheless, increased significantly from a mean baseline of 112 +/- 6 pg/ml to a mean peak of 158 +/- 19 pg/ml (P less than 0.005) at 20 min, although the magnitude of the response was substantially reduced (P = NS). These observations suggest that in the conscious dog, 2-DG stimulates SLI secretion in part via cholinergic mechanism.

Animals↗
PubMed1981

Origin of peripheral venous hypersomatostatinemia in alloxan-diabetic dogs.

Basal and postprandial somatostatin-like immunoreactivity (SLI) is elevated in the peripheral venous plasma of chronic alloxan-diabetic dogs. To determine if this hypersomatostatinemia was the consequence of increased somatostatin release from the pancreas, stomach, or both, plasma SLI was measured in the pancreaticoduodenal, antral, and fundic veins and in the inferior vena cava in response to stimulation by a gastric liver test meal, followed by an intragastric HCl load. Basal and postprandial inferior vena caval plasma SLI levels were significantly higher than the control level (P less than 0.05-0.001), confirming earlier findings. Basal pancreatic venous SLI was 780 +/- 45 pg/ml in the diabetic dogs and 493 +/- 65 pg/ml in the controls (P less than 0.02). In response to the liver meal at pH 7, the incremental pancreatic venous SLI level in the diabetic dogs was 1630 +/- 95 pg/ml, and after HCl it rose to 9479 +/- 384 pg/ml compared to 938 +/- 80 and 4677 +/- 192 pg/ml, respectively, in the controls (P less than 0.02 and P less than 0.005). However, antral and fundic venous SLI levels in the diabetic dogs did not differ from the controls in either basal or stimulated states. The present data demonstrate that the pancreas and not the stomach is the probable source of the peripheral hypersomatostatinemia of alloxan-diabetic dogs.

Animals↗
PubMed1981

Evidence for the hormonal status of somatostatin in man.

To determine the hormonal status of somatostatin in man, plasma levels of approximately 1600-dalton somatostatin-like immunoreactivity (SLI) were measured before and after a mixed meal. Plasma was subjected to gel filtration and the fractions coeluting with somatostatin were concentrated ninefold before radioimmunoassay. In this system the recovery of synthetic somatostatin added to plasma averaged 71 +/- 4.6% (mean +/- SE, N = 5). Synthetic somatostatin infused into normal volunteers gave a dose-related increase in the measured SLI value. Fasting SLI in 13 normal volunteers was 8.0 +/- 0.7 pg/ml (mean +/- SE) and rose to 18.6 +/- 1.5 pg/ml and 20.3 +/- 2.0 pg/ml at 60 and 120 min, respectively, after the meal (P less than 0.001). In seven type I diabetics, the fasting level was 11.5 +/- 1.6 pg/ml and the 60- and 120-min postprandial levels were 21.4 +/- 2.5 and 22.3 +/- 2.9 pg/ml, respectively. The meal-induced rise in approximately 1600 M.W. SLI approximated that produced by infusing somatostatin at 2 microgram/h, a rate that significantly suppressed glucagon levels. These results are therefore consistent with a hormonal role for somatostatin in man.

Adult↗
PubMed1981

High plasma free fatty acid levels contribute to the hypersomatostatinemia of insulin deficiency.

High plasma levels of free fatty acids (FFA) stimulate the secretion of splanchnic somatostatin, and both are elevated in insulin deficiency. To determine if the hypersomatostatinemia of insulin deficiency is secondary to high FFA levels, plasma somatostatin-like immunoreactivity (SLI) was measured in a group of insulin-deprived alloxan-diabetic dogs during nicotinic acid-induced lowering of their elevated plasma FFA to normal, and in a group of nondiabetic dogs during nicotinic acid-induced lowering of their FFA to subnormal values. In insulin-deprived diabetic dogs, nicotinic acid reduced plasma FFA from 1.07 +/- 0.2 (M +/- SE) mmol/L to 0.6 +/- 0.1 mmol/L (P less than 0.02), approximately the basal FFA level in normal dogs. This was accompanied by a significant decline in plasma SLI levels from a mean baseline of 247 +/- 15 pg/ml to a mean nadir of 199 +/- 10 pg/ml (P less than 0.005). The latter was, nevertheless, significantly above the basal SLI level of the nondiabetic dogs. In contrast, in normal dogs, nicotinic acid-induced reduction in FFA from 0.54 +/- 0.02 mmol/L to 0.24 +/- 0.03 mmol/L (P less than 0.001) was associated with only a small and inconsistent decrease in SLI. These findings suggest that the hypersomatostatinemia of insulin-deficient alloxan-diabetic dogs is, in part, secondary to high plasma FFA levels.

Animals↗
PubMed1980

Effect of bombesin upon plasma somatostatin-like immunoreactivity, insulin and glucagon in normal and chemically sympathectomized dogs.

The present study was designed to determine the effects of intravenously infused bombesin (10 ng/kg/min) upon basal and postprandial plasma somatostatin-like immunoreactivity (SLI), glucagon, insulin and triglyceride levels in normal (n = 12) and chemically sympathectomized (n = 11) dogs. Basal plasma SLI, glucagon and insulin levels rose significantly during the infusion of bombesin in the normal dogs, and this was not altered by chemical sympathectomy. Bombesin infusion enhanced the postprandial SLI response, while attenuating the postprandial glucagon response by 50% and the insulin response in the early postprandial phase of the meal. Sympathectomy did not significantly alter the basal levels of these polypeptides, but augmented the postprandial plasma SLI response during the first 90 min, and reduced the postprandial glucagon response during the infusion of bombesin. The postprandial insulin response was not affected by sympathectomy. In both normal and chemically sympathectomized dogs the rise in postprandial triglyceride levels was attenuated by bombesin infusion.

Animals↗
PubMed1980

Plasma Somatostatin-like immunoreactivity in chemically sympathectomized dogs.

The present study was designed to determine the role of the adrenergic nerves upon basal and postprandial gastric and pancreatic SLI release. In 19 chemically sympathectomized dogs peripheral venous plasma SLI levels in the basal and postprandial state were significantly below those of 30 controls for the first 135 min after the ingestion of a fat-protein meal. To determine the origin of this reduction, the SLI release from fundus, antrum and pancreas was studied in anesthetized dogs during the gastric phase of a meal at either pH 7 or pH 2. In response to a liver meal at pH 7 fundic, antral and pancreatic vein SLI levels were below the control and the rise in inferior vena cava SLI was abolished. In response to a liver meat at pH 2, the rise in antral and pancreatic vein SLI as clearly reduced in the sympathectomized dogs, while the decrease in fundic SLI was not influenced. The data demonstrate that adrenergic innervation plays a role in basal and postprandial SLI release from the stomach and pancreas.

Adrenergic Fibers↗
PubMed1980

Morphine-induced hyperglycemia: role of insulin and glucagon.

An iv bolus injection of 0.5 mg/kg morphine, about twice the therapeutic dose, caused plasma glucose to rise more than 120 mg/dl in alloxan-diabetic conscious dogs but had little effect on conscious normal dogs. Plasma glucagon rose in the diabetic and nondiabetic groups by 30 +/- 10 and 100 +/- 29 pg/ml, respectively, but insulin levels increased significantly only in the nondiabetics. The hyperglycemic action on morphine may, at least in part, be the result of an increase in glucagon secretion without a sufficient accompanying release of insulin.

Animals↗