Biomedical subjects

E R Trimble

Publications and source records attributed to E R Trimble.

At least 91 records · Page 5Linked to original sources

PubMed1984

Changes in content and secretion of pancreatic enzymes in the obese Zucker rat.

The contents of three major digestive enzymes (amylase, lipase and chymotrypsinogen) were measured in the obese Zucker rat. Only minimal changes were found in 7-week-old rats, but in adult obese rats (14-16 weeks) the amylase content was decreased by 50%, whereas the lipase and chymotrypsinogen contents were increased by 45% and 20%, respectively, compared with lean controls. Abnormalities of enzyme secretion were also found. Since the changes observed in enzyme proportions in adult obese Zucker rats are qualitatively similar to those observed in insulinopenic diabetes and other states associated with decreased glucose metabolism, it is speculated that the abnormalities found in the obese Zucker rat may be due to decreased glucose metabolism in the exocrine tissue consequent to insulin resistance.

Age Factors↗

PubMed1984

Modulation of beta-oxidation and proton conductance pathway of brown adipose tissue in hypo- and hyperinsulinemic states.

The metabolic capacity of interscapular brown adipose tissue of hypoinsulinemic (diabetic) rats is decreased and a reduced beta-oxidative capacity contributes to this metabolic alteration. It was thus of interest to compare, in diabetic and in chronically (8 days) insulin-infused rats, the beta-oxidative capacity and indices of the thermogenic state (GDP-binding and 32 000 Mr protein) in this tissue. Mitochondrial GDP-binding and 32 000 Mr protein were both decreased in diabetic rats compared to appropriate controls and markedly increased as was also the beta-oxidative capacity in hyperinsulinemic rats.

Adipose Tissue↗

PubMed1984

Insulin resistance in Type 1 (insulin-dependent) diabetes: dependence on plasma insulin concentration.

Sensitivity to insulin in vivo was studied in six Type 1 diabetic patients without residual insulin secretion and without clinical insulin resistance, and in eight non-diabetic subjects, using the euglycaemic insulin clamp technique. Insulin was infused for four periods of 2 h sequentially at 0.5, 1.0, 2.0 and 5.0 mU X kg-1 X min-1; for each insulin infusion period the steady-state plasma free insulin levels were comparable in the diabetic and non-diabetic subjects. The mean +/- SEM plasma glucose concentration was 4.9 +/- 0.03 mmol/l in the diabetic subjects (coefficient of variation of plasma glucose values: 5.7 +/- 0.7%) and 4.6 +/- 0.01 mmol/l in the control subjects (coefficient of variation: 5.1 +/- 0.6%). Insulin-mediated glucose disposal was lower in the diabetic than in the non-diabetic subjects at the two lower insulin infusion rates (mean +/- SEM = 2.03 +/- 0.27 versus 4.8 +/- 0.64 mg X kg-1 X min-1 at the first insulin infusion rate, p less than 0.01, and 5.59 +/- 0.59 versus 8.36 +/- 0.61 mg X kg-1 X min-1 at the second insulin infusion rate, p less than 0.01). However, insulin-induced glucose uptake did not differ significantly between the two groups at the third and fourth rates of insulin infusion. These results show that impaired insulin sensitivity in Type 1 diabetes is dependent on insulin concentration.

Adult↗

PubMed1984

In vivo stimulation of pancreatic hormone secretion by norepinephrine infusion in the dog.

Norepinephrine is generally regarded as an inhibitor of insulin release. It has been shown, however, that under hyperglycemic circumstances, norepinephrine infused at a high dose may also stimulate insulin secretion. The goals of this study were, under normoglycemic conditions, to confirm this stimulatory effect and to determine whether a beta-adrenergic mechanism or central neural pathways were involved. Secretion of pancreatic somatostatin and glucagon were also studied. Fasted, anesthetized dogs had norepinephrine (2 micrograms X kg-1 X min-1) infused into a peripheral vein for 60 min; blood was sampled from the pancreaticoduodenal vein. Norepinephrine stimulated insulin, somatostatin, and glucagon secretion without significant changes in either blood glucose concentration or pancreaticoduodenal venous blood flow. The stimulatory effect of norepinephrine on the three hormones was abolished by propranolol pretreatment, thus implicating a beta-adrenergic mechanism. Because bilateral cervical vagotomy prevented stimulation of insulin secretion by norepinephrine, central neural pathways must have been involved in the stimulatory process. However, norepinephrine-induced glucagon secretion was not decreased by vagotomy, showing that the stimulation was due to either a direct action on the pancreatic A cell or of a central pathway not mediated via the vagus nerve. Norepinephrine-induced somatostatin secretion was partly reduced by vagotomy, indicating that several mechanisms could be implicated.

Animals↗

PubMed1984

Effects of fenugreek seeds on endocrine pancreatic secretions in dogs.

The components of fenugreek seeds were separated and analyzed to determine which fraction of the seed had hypoglycemic activity. These fractions were administered orally to normal or diabetic dogs for 8 days. The effect on blood glucose and pancreatic hormones was studied in normal dogs. The lipid extract had no effect; the defatted fraction (50.2% fibers: gum 17.7%, hemicellulose 22%, cellulose 8.3%, lignin 2.2%) lowered basal blood glucose level, plasma glucagon and somatostatin levels and reduced the orally induced hyperglycemia. The addition of this fraction to the insulin treatment resulted in a decrease of hyperglycemia and glycosuria in diabetic dogs. The results indicate that the defatted part is responsible for the antidiabetic action. However, the present study does not permit one to know whether the effects are caused by an unknown pharmacological compound or by the gastrointestinal action of fibers.

Animals↗

PubMed1984

Glucose-induced somatostatin secretion by the rat pancreas is not potentiated by glucose.

The effect of previous exposure to glucose on subsequent glucose-stimulated insulin and somatostatin secretion has been investigated using the isolated perfused rat pancreas. As expected, when the pancreases of non-diabetic rats were exposed to 16.7 mM glucose on two occasions, 20 min apart, insulin secretion during the second period of exposure to high glucose was greater than that during the first period. By contrast, there was no potentiation of somatostatin secretion during the second glucose stimulation with respect to that of the first. Indeed, when the basal glucose concentration was low (1.4 or 2.8 mM) somatostatin secretion during the second glucose stimulation was lower than that during the first. Since exogenous insulin is known to inhibit glucose-induced somatostatin secretion, it seemed possible that lack of visible potentiation of glucose-induced somatostatin secretion by glucose could have been due to partial D cell inhibition by simultaneously augmented insulin secretion during the second glucose stimulation. In an attempt to exclude such an interaction between B and D cells, somatostatin secretion was also studied in the pancreases of spontaneously diabetic, Wistar (BB) rats (these animals are insulin deficient and are maintained by daily injections of insulin). However, even though insulin secretion was not detectable from these pancreases, glucose potentiation of glucose-induced somatostatin secretion did not occur. Although the pancreatic B and D cells are known to respond in a similar manner to many secretagogues the present results show that glucose potentiation of glucose-stimulated somatostatin secretion is not found under circumstances where potentiation of insulin secretion does occur. In addition, the absence of potentiated somatostatin secretion could not be attributed to partial inhibition of the D cell by insulin.

Animals↗

PubMed1984

Increased insulin responsiveness in vivo and in vitro consequent to induced hyperinsulinemia in the rat.

The effect of constant, controlled hyperinsulinemia on in vivo and in vitro insulin responsiveness has been investigated in rats that have received insulin infusions through chronically implanted jugular vein catheters. Constant rates of insulin infusion during days 1-4 resulted in stable plasma insulin concentrations. The plasma glucose initially fell from 122 +/- 3 to 53 +/- 4 mg/dl. While the infusion rate was maintained constant, the plasma glucose continued to fall over the subsequent days so that on day 4 the plasma glucose, 40 +/- 2 mg/dl, was significantly lower than that in the same animals on day 1 (P less than 0.02). Subsequently, the rate of insulin infusion was decreased to maintain the plasma glucose level in the 35-40 mg/dl range. Plasma catecholamine levels were high in insulin-infused rats. On the eighth day an in vivo insulin tolerance test (0.5 U/kg) was performed. Insulin-infused rats responded with a hypoglycemia that was both more pronounced and longer sustained than in saline-infused controls. Insulin responsiveness in vitro has been measured in isolated adipocytes. Adipocytes from epididymal fat pads were of similar size in the two groups of animals. Glucose uptake by adipocytes from insulin-infused rats was similar to that of controls under basal (zero insulin) conditions, but showed an increase in the maximum response to insulin. Glucose incorporation into total lipid and fatty acid was greater in adipocytes from insulin-infused rats than in controls under both basal (zero insulin) and insulin-stimulated conditions. Activities of the lipogenic enzymes acetyl CoA carboxylase and fatty acid synthetase were markedly increased in epididymal fat pads of insulin-infused rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase↗

PubMed1984

Glucose-insulin interactions on exocrine secretion from the perfused rat pancreas.

The effects of glucose and insulin on pancreatic enzyme release have been investigated using the isolated perfused rat pancreas. Basal and caerulein-stimulated secretion was significantly less in the presence of 15 mM glucose than with 5 mM glucose, except at a supramaximal concentration of caerulein (10(-9) M) where secretion was similar in both groups. Addition of exogenous insulin also caused a reduction in enzyme secretion, but the time of onset of the inhibitory action was delayed compared to that observed with glucose. Furthermore, it was found that the effects of 15 mM glucose and exogenous insulin were not additive at the concentration used in these experiments, and that the inhibitory action of insulin was glucose-dependent. Such glucose-insulin interactions must play an important role in the modulation of pancreatic enzyme secretion.

Amylases↗

PubMed1984

The effects of biliary obstruction on excretion of cefoperazone in the rat.

A study has been carried out on the influence of biliary obstruction on the elimination of cefoperazone (CPZ), an antibiotic mainly excreted in the bile. Rats were submitted to ligature of the common bile duct, given CPZ 100 mg/kg i.m., and killed 1 to 72 h afterwards. At death, measurements were made of CPZ concentrations in the serum, liver, lung, striated muscle, kidney, urine, intestinal wall and intestinal contents. The results were compared with those found in intact and in sham operated rats. Biliary obstruction led to a prolongation of the time taken for CPZ to disappear from the serum and markedly changed the way in which the drug was excreted. The amount of the drug excreted in the urine was 88% in the presence of biliary obstruction compared with 6% in intact rats and 14% in sham operated rats. The amount of CPZ in the small intestine 1 h after injection was very high in sham operated rats but only minimal amounts were found at this time in the presence of biliary obstruction. However, from 6 h after the injection, large amounts of CPZ were found in the intestinal contents despite the presence of biliary obstruction. In conclusion, in the presence of biliary obstruction, CPZ is eliminated by a combination of urinary and intestinal (non-biliary) excretion.

Animals↗

PubMed1983

[Sensitivity to insulin in type I diabetes. Preliminary report].

In vivo sensitivity to insulin was assessed by the euglycaemic insulin clamp technique in 5 type I diabetic subjects without residual insulin secretion and in 5 non-diabetic control subjects. Insulin was infused at increasing rates of 0.5, 1.0, 2.0 and 5.0 mU/kg/min in 4 periods of 2 hours. The diabetic subjects were resistant to insulin during the 1st and 2nd insulin infusion periods corresponding to the rates of 0.5 and 1.0 mU/kg/min, when compared to the non-diabetic subjects. However, glucose disposal rates were similar in the diabetic and control subjects at the 2 higher insulin infusion rates (2.0 and 5.0 mU/kg/min). Thus insulin resistance in type I diabetes is dependent on insulin concentration.

Adult↗

PubMed1983

Stimulation of pancreatic polypeptide secretion in the dog by hypoglycemic agent HB 699.

HB 699 is a hypoglycemic agent that has a structural similarity to glibenclamid but does not contain the sulfonylurea group. We have studied the effects of HB 699 and the sulfonylurea glipizide on pancreatic polypeptide (PP) and insulin secretion in the dog. Both HB 699 and glipizide stimulated insulin release and caused hypoglycemia in normal dogs. The secretion of PP was stimulated by HB 699 before the onset of hypoglycemia, whereas, following glipizide administration, PP secretion increased only after the onset of hypoglycemia. As expected, in alloxan-diabetic dogs neither substance affected plasma insulin or blood glucose levels. There was, however, a stimulation of PP secretion by HB 699 that was not observed with glipizide. It appears therefore that HB 699, in contrast to glipizide, stimulates PP secretion in the absence of any changes in circulating glucose and insulin concentrations. The direct action of HB 699 on the pancreas was shown by stimulation of insulin and PP secretion in the in vitro perfused uncinate process. In view of its direct pancreatic actions, HB 699 may prove a useful tool for further study of PP secretory mechanisms.

Animals↗

PubMed1982

[Glucagonoma syndrome in a multihormonal pancreatic tumor].

A 60-year-old patient developed signs and symptoms of glucagonoma syndrome (dermatitis, weight loss, anemia and hypoaminoacidemia). However, diabetes mellitus was absent. Glucagonoma was suspected because of markedly elevated plasma glucagon levels and the tumor was subsequently removed by surgery. Acidethanol extraction of the tumor and immunohistochemistry provided evidence of the presence of all four islet hormones, particularly that of glucagon and pancreatic polypeptide and to a lesser extent of somatostatin and insulin. Immunohistochemistry of the tumor (but not plasma) also showed the presence of alpha-HCG. Plasma glucagon immunoreactivity consisted to a large extent (approx. 90%) of a high molecular form of glucagon, probably proglucagon. In spite of the presence of alpha-HCG - which is assumed to be a marker of malignancy - the patient has been free of recurrence for the 2 1/2 years since surgery. The increasing number of cases reported during the past few years demonstrates that the syndrome is more common than previously suspected. Glucagon secretion and its typical clinical picture may be a valuable marker of a multihormonal pancreatic tumor. In a case of suspected glucagonoma, diagnosis can be established simply by obtaining a plasma glucagon level measurement.

Adenoma, Islet Cell↗

PubMed1982

Functional differences between rat islets of ventral and dorsal pancreatic origin.

Do functional linkages between islet endocrine cells exist? The effect of differences in frequency and distribution of islet endocrine cells on B cell function was examined in islets from the ventral (ventral islets) and dorsal (dorsal islets) areas of the rat pancreas. Dorsal islets contained 10 times as much glucagon as ventral islets, whereas insulin and total protein contents were similar. Basal rates of insulin secretion and proinsulin biosynthesis were similar in the two types of islet, but, under conditions of glucose stimulation, both insulin secretion and proinsulin biosynthesis were significantly greater in the glucagon-rich dorsal islets. Similarly, glucose utilization rates an ATP levels were greater in dorsal islets. In contrast, the rates of processing of newly synthesized proinsulin were similar in ventral and dorsal islets. That the islet glucagon content may have affected B cell function is inferred from two independent findings. Firstly, basal and glucose-stimulated cyclic AMP contents of glucagon-rich dorsal islets were greater than those of ventral islets. Secondly, in the presence of excess exogenous glucagon (1 microgram/ml), the differences in glucose-induced insulin secretion and proinsulin biosynthesis rates between the two types of islets were eliminated. These results strongly suggest that changes in the relative proportions of the different islet endocrine cells exert marked effects on islet function. In particular, a greater A cell and glucagon content is associated with higher rates of glucose-induced insulin secretion and biosynthesis.

1-Methyl-3-isobutylxanthine↗

PubMed1982

Effects of synthetic human pancreatic polypeptide, synthetic bovine pancreatic polypeptide, and the C-terminal hexapeptide on pancreatic somatostatin and glucagon secretion in the rat.

Synthetic human pancreatic polypeptide stimulated pancreatic somatostatin secretion by isolated rat islets and by the isolated perfused rat pancreas. In contrast, synthetic bovine pancreatic polypeptide and the C-terminal hexapeptide had no effect on somatostatin secretion. Synthetic human pancreatic polypeptide had only a mild stimulatory effect on glucagon secretion at the highest concentration of the peptide used (2.2 x 10(-6) M0 and in the presence of 16.7 mM glucose.

Animals↗

PubMed1982

[Effect of chronic administration of an acylamino alcoyl derivative of benzoic acid, HB 699, on the pancreatic polypeptide secretion in the dog].

HB 699, a hypoglycemic and insulin stimulating agent, which does not belong to the sulphonylurea group, was administered per os to the dog at the dose of 15 mg/kg, daily for 14 days. This agent induced an increase in fasting plasma levels of pancreatic polypeptide, without modifying blood glucose, insulin, glucagon and somatostatin levels.

Administration, Oral↗

PubMed1981

Effect of a new hypoglycaemic agent (HB 699) on the in vivo secretion of pancreatic hormones in the dog.

The effects of HB 699, a non-sulphonyl urea acyl-amino-alcyl benzoic acid derivative, were studied in unanesthetized dogs. Changes in blood glucose and plasma insulin, glucagon, pancreatic polypeptide and somatostatin were measured after a single intravenous injection. HB 699 caused hypoglycaemia and stimulated insulin secretion in a dose-dependent manner. The effects of HB 699 (40 mg/kg) on pancreatic hormone secretion were compared to those of tolbutamide give at a dose (12 mg/kg) which induced a similar maximal hypoglycaemia. Both drugs caused a similar increase in insulin release (180 +/- 32% for tolbutamide and 240 +/- 41% for HB 699) lasting for approximately 1 hour. Despite hypoglycaemia, plasma glucagon concentrations were unaltered by either substance. HB 699 caused a marked increase in the secretion of pancreatic polypeptide (220 +/- 60% at 30 min) for up to 2 hours, whereas tolbutamide caused no significant change in plasma pancreatic polypeptide levels. In contrast, while tolbutamide caused a significant (45 +/- 12%) but short-lived increase in plasma somatostatin concentrations, HB 699 had no significant effect.

Animals↗

PubMed1981

Ventral and dorsal areas of rat pancreas: islet hormone content and secretion.

Islets isolated from the dorsal and ventral areas of the rat pancreas (dorsal and ventral islets) were found to have similar insulin and total protein contents. Dorsal islets, however, contained more glucagon and somatostatin than ventral islets. Dorsal islets secreted significantly more insulin in the presence of 16.7 mM glucose and 20 mM D-glyceraldehyde than did ventral islets. Leucine-induced (20 mM) insulin secretion from the two types of islet was similar. The amounts of somatostatin secreted by the two types of islet were similar both in the presence of 16.7 mM glucose and in the presence of 20 mM D-glyceraldehyde. By contrast, more glucagon was secreted by dorsal than by ventral islets in the presence of 16.7 mM glucose. It was found that the difference in glucagon secretion between the dorsal and ventral islets in the presence of 16.7 mM glucose may be an explanation for the difference in the rate of insulin secretion under these conditions. The results suggest that glucagon may exert an important intraislet control on insulin secretion.

Animals↗

PubMed1981

Importance of cholinergic innervation of the pancreas for glucose tolerance in the rat.

Because cholinergic innervation of the pancreas is of importance in control of oral glucose tolerance, it seems important to determine whether transplanted pancreatic tissue becomes reinnervated with cholinergic fibers. Oral and intravenous glucose tolerance tests (ivGTT) were performed with and without atropine treatment on streptozotocin-diabetic rats treated by intraportal transplantation of isogenic islets 13-15 wk previously and on sham-operated nondiabetic controls. Atropine had no effect on the ivGTT of transplanted rats or controls. In controls atropine caused a deterioration of the oral glucose tolerance, abolished the preabsorptive insulin release, and also diminished the early part of the glucose-induced insulin release in these animals. In the absence of atropine, transplanted rats had pathological oral glucose tolerance, preabsorptive insulin release was absent, and glucose-induced insulin release was diminished compared to controls. Atropine had little effect on the oral GTT of transplanted rats. The present results underline the importance of the vagus nerve in the control of oral glucose tolerance and show that the vagus nerve in rats, at least under these experimental conditions, does not modulate the insulin response to intravenous glucose. The results suggest that intraportally transplanted islets remain functionally vagotomized.

Animals↗