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E R Trimble

Publications and source records attributed to E R Trimble.

At least 109 records · Page 6Linked to original sources
PubMed1981

Effect of insulin on glucose- and arginine-stimulated somatostatin secretion from the isolated perfused rat pancreas.

The effects of exogenous insulin on somatostatin secretion from the isolated perfused rat pancreas have been investigated in the presence of 5.6 mM glucose and when somatostatin secretion was stimulated by either glucose (16.7 mM) or arginine (20 mM). Insulin (15 mU/ml) significantly and rapidly suppressed glucose- and arginine-stimulated somatostatin release. However, at 5.6 mM glucose and, in the absence of other stimulators of somatostatin release, insulin had no effect on the somatostatin secretion rate.

Animals↗
PubMed1981

Glucose and cyclic AMP as stimulators of somatostatin and insulin secretion from the isolated, perfused rat pancreas: a quantitative study.

The secretory responses of beta and delta cells were compared in the isolated, perfused, rat pancreas. Insulin release was stimulated 50-fold and somatostatin (SRIF) secretion twofold when the glucose concentration was increased from 100 mg/dl to 300 mg/dl. When islet cyclic AMP (cAMP) was raised by 3-isobutyl-1-methylxanthine (IBMX), the secretion of SRIF was stimulated in a glucose-dependent manner (300 mg/dl greater than 100 mg/dl greater than 25 mg/dl). As expected, insulin release was also potentiated in a similar fashion. A difference in the glucose dependency of the cAMP effect was seen at 25 mg/dl glucose, where 0.25 mM IBMX enhanced the release of SRIF but not that of insulin. In contrast, at 300 mg/dl glucose, IBMX caused a greater potentiation of insulin release than of SRIF release. The release of insulin, when expressed in absolute terms, was stimulated more markedly than that of SRIF under most conditions tested. However, the expression of total hormone released during 30 min of stimulation as a percentage of tissue hormone content allowed a different interpretation of the results. For example, 2.1% and 1.8% of tissue insulin and SRIF contents, respectively, was released during exposure to 300 mg/dl glucose. Surprisingly, under basal conditions (100 mg/dl glucose), 1.0% of total SRIF content was released during 30 min compared with the release of only 0.04% of insulin.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Abnormalities of pancreatic somatostatin secretion corrected by in vivo insulin treatment of streptozotocin-diabetic rats.

In islets removed from untreated streptozotocin-diabetic rats, the somatostatin-containing cells were unresponsive to changes in glucose concentration, while they did respond to raised cyclic AMP levels. By contrast, in vivo insulin treatment restored the glucose sensitivity of the somatostatin secreting cells. In addition, in vivo insulin treatment resulted in a lowering of the high basal somatostatin secretion rate found in islets from untreated diabetic rats. These changes were made without any alteration of islet insulin content or enhancement of the in vitro insulin secretion. These results indicate that there is not a basic defect in the glucoreceptor of the somatostatin cell in diabetes.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Cephalic phase, reflex insulin secretion. Neuroanatomical and physiological characterization.

Using chronically catheterized, freely moving male Wistar rats, we have shown that the sweet taste of a saccharin solution reliably triggers a rapid cephalic phase insulin response (CPIR), in the absence of any significant change of glycemia. To establish the neural mediation of this reflex response we used rats that were cured from streptozotocin diabetes by intrahepatic islet-transplantation as a denervated B-cell preparation. The complete lack of any saccharin-induced CPIR in these rats suggests that it is indeed mediated by the peripheral autonomic nervous system, and that the insulin-stimulating gastrointestinal hormones are not involved in this response. It was further found that this reflex insulin secretion is not easily extinguishable and thus might have an unconditioned component. To investigate the central neural pathways involved in this reflex response we used both electrophysiological methods in anesthetized and semi-micro CNS manipulations in freely moving rats. On the basis of our preliminary results, and several reports, using the decerebrate rat preparation for measuring behavioral or saliva secretory oral taste reactivity, it appears that the CPIR might be organized at the brain stem/midbrain level, receiving strong modulatory influences from the diencephalon. But much further work has to be done to establish the central nervous circuitry. Finally, in two experiments, aiming at the question of how important and physiologically relevant the CPIR might be, we found that, on one hand, its lack can result in pathological oral glucose tolerance and on the other hand its exaggeration might contribute to the behavioral reaction to highly palatable sweet food and the resulting development of dietary obesity.

Animals↗
PubMed1981

Comparison of insulin secretion by the isolated perfused pancreas and perifused islets of the spiny mouse (Acomys cahirinus).

The dynamics of glucose-stimulated insulin release were studied in the perfused pancreas and in isolated perifused islets of spiny mice. The pattern of insulin release induced by an increase of the glucose concentration from 2.8 mM to 16.7 mM was different in the two preparations. In the perfused pancreas there was an early insulin release contrasting with an absence of the early response in isolated islets. The later insulin release response (5 min to 30 min) was present and similar in both preparations. The reduction of early phase insulin release may be due to a reduced glucose sensitivity in the beta cells of spiny mice, most apparent in isolated islets.

Animals↗
PubMed1980

Importance of preabsorptive insulin release on oral glucose tolerance: studies in pancreatic islet transplanted rats.

The role of preabsorptive (cephalic phase) insulin release in oral glucose tolerance was investigated using diabetic rats treated by intraportal transplantation of isogenic islets. This early neurally mediated phase of insulin release has been shown to be absent in such rats. When the body weight of transplanted rats was normalised, glucose tolerance tests (GTTs) were performed in the unstressed state using permanent cardiac catheters. Transplanted rats had a normalised intravenous GTT, whereas, as we have shown previously, their oral GTT remained clearly pathological. During both tests peripheral insulin levels were decreased compared with controls. While during intravenous GTT the onset of insulin release occurred as early in transplanted rats as in controls, during oral GTT there was a clear delay, probably because of the absence of the cephalic phase. Re-establishment of normal preabsorptive insulin levels was attempted by a small intravenous insulin injection during this period. This resulted in a transient increase in peripheral insulin levels, which, at two minutes after glucose ingestion, gave values similar to those found in controls at that time. This small insulin injection caused a marked improvement of the oral GTT which was most evident after exogenous insulin had disappeared from the blood. While the injection did not affect the 60 minute incremental insulin area, the glucose area was decreased by 50%, to a value not significantly different from that of control rats. The cephalic phase of insulin release appears, therefore, to be one important factor in the control of glycaemia during food intake. Its absence plays a major role in the pathological oral glucose tolerance of diabetic rats treated by intraportal islet transplantation.

Animals↗
PubMed1980

Cephalic-phase insulin secretion in normal and pancreatic islet-transplanted rats.

The ability of saccharin, in comparison with glucose and tap water, to elicit glycemia-independent neurally mediated insulin secretion was investigated in chronically catheterized, freely moving rats. Plasma glucose and insulin concentrations were measured continuously from venous blood with a sampling resolution of one per minute. In normal rats, 1 ml of 0.15% saccharin caused a significant rapid rise in peripheral plasma insulin levels lasting up to 5 min, without significant changes in glycemia. Tap water alone also induced a transient elevation in insulinemia but was much smaller than the saccharin-induced response. In streptozotocin diabetic rats bearing intrahepatic, presumably denervated islet isografts, these rapid insulin responses to oral saccharin and tap water stimulation were completely abolished, whereas the early insulin response to intravenous glucose was decreased by only about 30%. These results are consistent with the concept of gustatory and other oral sensory signals acting as triggers for neurally mediated insulin release.

Animals↗
PubMed1980

Intraportal islet transplantation: functional assessment in conscious unrestrained rats.

We have found that rats with transplanted pancreatic islets, when compared to normal rats, have a delayed onset of insulin release in response to orally, but not to iv administered glucose. Furthermore, while glucose tolerance of the rats with transplanted islets was similar to that of normal controls when the glucose was administered iv, the tolerance was markedly less when it was administered orally. These tests were carried out using permanently implanted cardiac catheters and chronic oral fistulae and were conducted at a time when the body weight of the transplanted animals had returned to levels similar to those of the controls. During the tests the rats were conscious and unrestrained. The difference in the fine control of insulin secretion in transplanted islets from that in the normal pancreas may be due to defective innervation of such islets. These results may have implications for the use of transplanted islets in the control of diabetes mellitus in man. The methods employed can be further used to define other areas in which the response of transplanted islets in rats differs from that of the normal pancreas.

Animals↗
PubMed1980

Plasma glucagon and insulin concentrations in acromegaly.

Sixteen patients with clinically active acromegaly were investigated; four of these had insulin-independent diabetes mellitus. Those acromegalic subjects who were not diabetic exhibited excessive insulin responses to glucose and arginine stimulation. By contrast, plasma glucagon concentrations in these patients did not differ significantly from those in control subjects. Acromegalic patients who also had insulin-independent diabetes had a markedly reduced insulin response to glucose stimulation, while arginine-induced insulin secretion was relatively well preserved. Although there was a tendency for plasma glucagon concentrations to be higher in the diabetic than in the nondiabetic group of acromegalic subjects, this difference did not achieve statistical significance either in the basal state or during the glucose amd arginine infusion tests.

Acromegaly↗
PubMed1980

Hypersection of pancreatic somatostatin in the obese Zucker rat: effects of food restriction and age.

Islets of 5-mo-old obese Zucker rats secreted 50% more somatostatin (SRIF) in response to 8.3 mM or 16.7 mM glucose than did islets from lean controls; the islet SRIF contents of obese and lean rats were similar. As expected, islets of obese rats demonstrated a greater basal and a fivefold greater glucose-induced insulin release and also a twofold greater insulin content than did islets from lean rats. Obese rats were pair fed with lean animals from the age of 9 wk until killed, when 5 mo old. While this curtailed the weight gain of obese rats to that of lean controls, it caused no reduction in the percent body weight found in the form of lipid. The responses of the pancreatic delta and beta cells to pair feeding were markedly different. Pair feeding caused no alteration in either SRIF content or glucose-induced SRIF release, while the expected reductions in both islet insulin content and glucose-induced insulin secretion were observed. Islets from older obese Zucker rats (15--18 mo old) had four to five times greater contents of both SRIF and insulin than did islets from age-matched lean controls. The obese rats of this age had a moderate glucose intolerance. SRIF secretion from the islets of such rats was distinctly greater than from those of lean controls at all glucose concentrations tested (range, 1.0--16.7 mM). The delta cells of the older obese rats had lost their sensitivity to glucose, while those of lean controls remained sensitive. Beta cells of islets from both obese and lean 15-mo-old rats remained glucose sensitive. Under all conditions tested, secretion of SRIF and insulin was greater from islets of obese than lean rats. The results demonstrate a marked difference in pancreatic delta and beta cell responses to pair feeding in the obese Zucker rat. At present, the role played by hypersecretion of pancreatic SRIF in the obesity syndrome of the Zucker rat remains obscure.

Aging↗
PubMed1980

Effects of intraportal islet transplantation on the transplanted tissue and the recipient pancreas. I. Functional studies.

It is well known that, in diabetes, there is an abnormality of both pancreatic beta and alpha cell secretion. Since islet transplantation can markedly improve the diabetic state in streptozotocin-treated rats, we investigated the effects of intraportal transplantation on the beta and alpha cell secretion of the transplanted tissue. In addition we examined the effects of transplantation on the hormone content of both the transplanted tissue and the endogenous pancreas. Animals were examined 6 and 20 wk after transplantation. Isolated perfusions of the perfusions of the islet-containing livers showed that both glucagon and insulin secretion could be promptly stimulated by arginine. The hormone content of the livers at death revealed that, while the insulin content of transplanted tissue was well maintained, there was a marked reduction in glucagon content. An increase in pancreatic glucagon content was found in rats with untreated diabetes of five months' duration; this was partially or fully prevented by islet transplantation. There was also a moderate increase in insulin content of the pancreases of animals that received islet transplants.

Animals↗
PubMed1979

Progressive visual failure in acromegaly following external pituitary irradiation.

Four out of twenty-three acromegalic patients selected for treatment with external megavoltage pituitary irradiation between 1961 and 1975 developed progressive visual failure. They had received megavoltage external irradiation through multiple portals from a cobalt-60 unit over a period of 3 weeks. Visual deterioration began 2 months to 6 years after irradiation. In two patients the optic nerves were explored. In both, post-mortem later confirmed radiation damage to the optic nerves and hypothalamus. In one case there was also necrosis of the right frontal lobe with necrosis and inflammation of the bone surrounding the pituitary fossa. In the two other patients, extensive clinical and neuroradiological investigation excluded the presence of a suprasellar mass as a cause for this visual failure and a clinical diagnosis of radiation necrosis was made.

Acromegaly↗
PubMed1977

Insulin and glucagon response to arginine infusion in cystic fibrosis.

The glucagon and insulin responses to intravenous arginine were studied in 17 children with cystic fibrosis and in 9 control children. It was found that the overall secretion of insulin was diminished; however, four of the CF children did have a normal output. The glucagon responses did not parallel those of insulin. The glucagon output varied in the CF children--seven had normal, four excessively high and six low output. Three of the four children with extremely high output had more severe disease and were below the third centile on the weight chart. These four had a fasting hypoglycaemia and also a very low glucose and insulin response. We have confirmed diminished insulin secretion in cystic fibrosis, but diminished glucagon secretion was only noted when some insulin secretion was preserved. The high levels of glucagon seen in the most insulin deficient subjects may be derived from extrapancreatic sources, or may be associated with 'stress' reaction in these patients who also had most severe pulmonary involvement. The data would be consistent with diminished glucagon and insulin secretion from the pancreas but as the disease progresses an excessive secretion of extra pancreatic glucagon results.

Arginine↗
PubMed1977

Secretin: high plasma levels in diabetes mellitus.

Plasma immunoreactive secretin levels were measured in 22 newly diagnosed non-ketotic, maturity-onset diabetics and 10 healthy control subjects during 50 gram oral glucose tolerance test (OGTT). The test was repeated in the diabetic group after 6 months' dietary treatment. At diagnosis the fasting secretin levels in the diabetics were higher than in control subjects but fell within the normal range following dietary treatment. In the diabetics there was a significant positive correlation between the fasting glucose and fasting secretin levels at the time of diagnosis. Suppression of secretin levels occurred during the OGTT, both in diabetic and control subjects.

Diabetes Mellitus↗
PubMed1976

High circulating levels of glucagon and gastrin in anephric subjects.

Six nephrectomised patients undergoing chronic haemo-dialysis and six patients who have had renal transplantation were studied in comparison with a control group of healthy subjects. Their glucose, insulin, glucagon and gastrin levels were measured during a 50g oral glucose tolerance test which, in the dialysis group, was carried out just prior to a dialysis period. In this group fasting blood samples were obtained also on the morning immediately following dialysis. Glucagon levels were high in the dialysis group and gastrin levels were raised in both the dialysis and transplant groups. These abnormalities may be related to some of the clinical features of renal failure.

Adult↗