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Biomedical subjects

R Ebert

Publications and source records attributed to R Ebert.

At least 73 records · Page 4Linked to original sources
PubMed1985

New developments in the incretin concept.

Experimental and clinical work over the last 6 years has confirmed and broadened, but also challenged, the incretin concept. The nervous component of the entero-insular axis is still poorly defined, especially the peptidergic nerves, of which several contain insulinotropic regulatory peptides. The incretin effect is preserved after complete denervation of the porcine pancreas. Type 2 (non insulin-dependent) diabetic patients have a significantly decreased incretin effect. GIP (gastric inhibitory polypeptide; glucose dependent insulin releasing peptide) remains the strongest incretin factor. Its secretion depends on the absorption of nutrients. However, the correlation between the GIP response and disturbances of the entero-insular axis in some gastrointestinal diseases and, in particular, Type 2 diabetes, is poor. Furthermore, physiological concentrations of exogenous GIP do not produce fully the incretin effect and injection of GIP antibodies does not abolish the incretin effect. This suggests the existence of additional humoral incretin factors. On the other hand, GIP seems to have direct metabolic effects independent of its insulinotropic activity. The incretin effect of oral glucose is smaller if plasma levels of C-peptide rather than insulin are measured. However, decreased hepatic extraction of insulin after glucose ingestion only accounts partially for the incretin effect. GIP is unlikely to be the gut factor which regulates hepatic insulin extraction.

Animals↗
PubMed1985

Preserved incretin effect after complete surgical denervation of the pancreas in young pigs.

Plasma insulin responses to intragastric (i.g.) (1.5 g/kg b.wt.) and "isoglycemic" intravenous (i.v.) glucose were measured in ten unanesthetized young pigs to assess the contribution of gastrointestinal factors to the total insulin secretion as observed after i.g. glucose. The participation of nerves was estimated by comparing metabolic tests performed before and after total surgical pancreatic denervation. In the five animals which survived the procedure, 52.6% of the insulin response after i.g. glucose was calculated to be due to incretion factors, a value similar to the 54.8% found in the preoperative series (with intact pancreatic innervation). The response of IR-GIP to i.g. glucose was not significantly different between preoperative and postoperative tests, although a subtotal duodenectomy had to be performed in the course of the operation designed to completely denervate the pancreas. Intragastric and i.v. (also tested by bolus glucose injection) glucose tolerance was almost identical before and after the operation. It was concluded that nerves do not seem to play a major role in mediating the incretin effect in pigs. Hormonal factors, including GIP, appear to be more important.

Animals↗
PubMed1985

Effect of dialysate glucose load on plasma glucose and glucoregulatory hormones in CAPD patients.

The effect of a dialysate exchange with both 1.5 and 4.25% glucose solutions on plasma levels of glucose, insulin, gastric inhibitory polypeptide (GIP), and glucagon has been investigated in 5 continuous ambulatory peritoneal dialysis (CAPD) patients. Only in the case of the 4.25% solution did plasma glucose levels rise above 100 mg/dl. 4 of the 5 patients responded to this change with a marked insulin secretion. Employing the 1.5% solution, plasma glucose remained stable and only a slight insulin stimulation was observed in 2 patients. It is concluded that provided the 4.25% dialysates are used only occasionally, there will be no continuous stimulation of the pancreatic beta-cells due to absorption of glucose from the dialysate alone during CAPD treatment. GIP levels are highly elevated in CAPD patients. A dialysate exchange with either a 1.5 or a 4.25% glucose solution had no effect on this gastrointestinal hormone. Hyperglucagonemia was also observed in this collective. An initial suppression of glucagon levels occurred in 4 of the patients after a 4.25% dialysate exchange. The 5th patient demonstrated an initial rise followed by a later decrease in glucagon, a response similar to that reported in adult onset diabetes after an oral glucose tolerance test.

Adult↗
PubMed1984

Hyperinsulinaemia in non-cirrhotic haemochromatosis: impaired hepatic insulin degradation?

This study investigated early alterations of glucose metabolism in idiopathic haemochromatosis. Circulating concentrations of glucose, insulin, C-peptide, glucagon, and gastric inhibitory polypeptide (GIP) were measured after a 100-g oral glucose load in 10 men with idiopathic haemochromatosis in the non-cirrhotic stage of the disease. All had normal glucose tolerance and normal body weight. Ten matched healthy subjects were studied as controls. Insulin concentrations increased to significantly higher levels in patients with idiopathic haemochromatosis than in the control subjects from 30 to 180 min after the glucose load (p less than or equal to 0.01), while fasting insulin concentrations were not significantly different (p greater than 0.05). Concentrations of glucose, glucagon, C-peptide, and GIP were not significantly different at any time (p greater than 0.05). Thus, patients with idiopathic haemochromatosis show hyperinsulinaemia and hence insulin resistance without impaired glucose tolerance in the non-cirrhotic stage. Since pancreatic insulin secretion (C-peptide), glucagon secretion, and the entero-insulinar axis (GIP) are not impaired in these non-cirrhotic patients with idiopathic haemochromatosis, iron accumulation in the hepatocytes may be responsible for the impaired insulin effect and may cause impaired hepatic insulin extraction.

Adult↗
PubMed1984

Recovery from effects of brief monocular deprivation in the kitten.

The potential for recovery from the cortical effects of monocular deprivation (MD) was studied in kittens that were briefly deprived and then exposed to various periods of normal binocular vision. In eight kittens, recordings from the hemisphere ipsilateral to the deprived eye revealed that at 4 wk of age, exposure to 12 h of MD (six 2-h sessions spread over 2 days) was sufficient to cause a massive shift in the ocular dominance of striate cortex neurons in favor of the nondeprived eye. Six of these MD kittens were allowed 3 wk of normal binocular vision and then recorded from a second time to assess the extent to which their cortex could recover from the effects of this brief period of deprivation. Data from these animals indicated that now approximately equal numbers of cortical neurons were dominated by each eye and that, while the overall level of binocularity was somewhat lower than that found in normally reared animals, the majority of cells had regained functional binocular connections. The possibility that cortical binocularity could recover even further was explored by allowing four of these six MD kittens to experience an additional 4 wk of binocular vision and then recording from them a third time. These final recordings indicated that following a total of 7 wk of binocular vision, the level of cortical binocularity was no different from that found in normally reared animals. Having demonstrated that normal binocular function can be restored to a cortex in which it had been severely disrupted, we next attempted to characterize the earliest stages of this recovery process by examining the pattern of cortical binocularity in 10 MD kittens that were allowed to experience either 6 or 12 h of binocular vision (given over 1 or 2 days, respectively). Our results indicate that, during the initial day of binocular vision, recovery seems to involve a noncompetitive expansion of functional cortical input from the deprived eye, which joins with input from the nondeprived eye in driving cortical neurons. The level of cortical binocularity continues to increase during the next day of binocular vision, but now there is also a small increase in the proportion of cells driven exclusively by the initially deprived eye--suggesting that there may be an additional competitive component to the early stages of recovery. The results of this study complement our previous report of complete recovery of binocularity following exposure to a brief period of optically induced strabismus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Elevated plasma cholecystokinin concentrations in exocrine pancreatic atrophy in the rat.

Rats were fed with a copper-deficient diet combined with penicillamine to produce an atrophy of the exocrine pancreas by selective destruction of the acinar cells, which are replaced by fat cells. Plasma cholecystokinin (CCK) concentrations in animals with exocrine pancreatic atrophy were 250% higher compared to control animals (21.7 +/- 7.8 vs. 6.1 +/- 1.07 pmol/l; p less than 0.001). Plasma concentrations of gastrin were significantly decreased by 44% and of gastric inhibitory polypeptide (GIP) significantly increased by 24%, while the decrease of the plasma insulin did not reach the level of significance. In the proximal duodenum a significant decrease of the CCK concentration could be observed, whereas tissue concentrations of GIP in duodenum and jejunum and gastrin in the gastric antrum remained unaltered. These data suggest that the negative feedback control of pancreatic enzyme secretion is mediated by the release of CCK.

Animals↗
PubMed1984

Preceding hyperinsulinemia prevents demonstration of insulin effect on fat-induced gastric inhibitory polypeptide (GIP).

The effect of insulin on fat-induced gastric inhibitory polypeptide (GIP) release has been studied in seven healthy volunteers during euglycemic blood glucose clamping. In the first protocol, insulin (0.1 U/kg/h) was infused 2 h before ingestion of 100 g fat and continued for 2 h thereafter. In protocol II, saline was infused 2 h before the fat load and the insulin infusion started at the time of fat ingestion. During both insulin infusion studies, glucose levels were clamped at the fasting level by means of the Biostator and plasma levels of insulin, C-peptide, and GIP were estimated by radioimmunoassay. The response of GIP to oral fat was inhibited by 63% if insulin infusion was started at the time of fat ingestion, whereas no inhibition was seen if a 2-h hyperinsulinemic period preceded the fat load. The plasma insulin levels were comparable at the end of each experiment, ranging from 110 to 130 microU/ml. Plasma C-peptide levels decreased during the insulin infusion and increased after fat ingestion. These findings were not the result of inhibition of gastric emptying by insulin because they could be confirmed in four volunteers with intraduodenal infusion of fat. The present data show that insulin does inhibit fat-induced GIP secretion in normal man, but preceding hyperinsulinemic glucose clamping masks this insulin effect, probably by decreasing the sensitivity of the GIP cells to insulin.

Adult↗
PubMed1984

Role of gastrointestinal transit in the delay of absorption by viscous fibre (guar).

The influence of guar gum on gastric emptying of liquids in healthy volunteers and on mouth-to-caecum transit time in controls and partially gastrectomized patients has been studied. Together with a flattening effect on blood glucose profiles after a liquid glucose load, guar significantly delays mouth-to-caecum transit time both in healthy controls and partially gastrectomized patients. The retardation of transit is not explicable by a delay in gastric emptying, as can be shown by means of an isotope technique. Only in "quick starters' was a delay in initial gastric emptying observed. The exponential phase of gastric emptying remained unaffected. Moreover, it is shown that the prolongation of mouth-to-caecum transit time is not mediated by factors operating at the level of the pyloricantral region. Delayed small-bowel passage by guar might modulate absorption of glucose by increasing the unstirred layer resistance and, in the non-steady state, by limiting the absorptive area initially covered by a bolus.

Adult↗
PubMed1984

Different response of gastric inhibitory polypeptide to glucose and fat from duodenum and jejunum.

Gastric inhibitory polypeptide (GIP), insulin, and blood glucose after ingestion of glucose or fat were examined in patients after gastrectomy with esophagojejunostomy or esophagoduodenostomy. After a glucose load patients without duodenal passage had significantly higher glucose and significantly smaller insulin levels than patients with duodenal passage. The fasting levels of serum immunoreactive GIP were moderately elevated and reached significantly higher levels after oral glucose ingestion in both gastrectomized groups as compared with normal subjects. In patients with preserved duodenal passage serum IR-GIP levels peaked earlier and were significantly higher than in patients without duodenal passage. In contrast to the finding after oral glucose ingestion, the IR-GIP response to an oral fat load was nearly twofold greater in patients without duodenal passage than in patients with duodenal continence. Thus, glucose-induced GIP release is mainly of duodenal and fat-induced GIP release mainly of jejunal origin. This suggests the existence of two types of GIP cells.

Adult↗
PubMed1983

Preservation of incretin activity after removal of gastric inhibitory polypeptide (GIP) from rat gut extracts by immunoadsorption.

The action of watery rat gut extracts on glucose-induced insulin release in anaesthetized rats was examined before and after removal of GIP by immunoadsorption. Infusions of GIP-containing rat gut extracts nearly doubled the insulin release induced by intravenous glucose (1 g X kg -1 X h -1). Peak insulin secretion was 98 +/- 11 mU/l (mean +/- SEM) after intravenous glucose and increased to 178 +/- 16 mU/l following infusion of glucose plus gut extract (p less than 0.005). After injection of GIP antiserum in sufficient amounts to neutralize the GIP activity in the gut extract preparation, the additional insulin release due to the gut extract was reduced by only 30%. After complete removal of GIP from gut extracts by immuno-absorption, more than 50% of the incretin effect remained. These data suggest that the insulinotropic activity of rat gut extracts can only be partially related to GIP. The existence of additional insulinotropic gut factors which may also be released following oral glucose is postulated.

Animals↗
PubMed1983

Inhibition of gastric secretion by fat and hypertonic glucose in the dog: role of gastric inhibitory peptide.

1. The gastric and intestinal phases of gastric secretion were selectively evoked by 'meals' of 5% liver extract or saline in five dogs provided with a special cannula that allowed complete separation of the stomach from the duodenum. 2. The gastric phase in response to liver extract administered into the stomach amounted to an increase in acid output equivalent to about 70% of the maximum output in response to histamine. There was also a significant rise in the concentration of gastrin but not of gastric inhibitory peptide (GIP) in the serum. 3. The addition of fat (2 or 4% corn oil) or glucose (20%) to this liver extract meal inhibited secretion of gastric acid by 50 and 30%, respectively, without affecting the concentration of gastrin or GIP in the serum. 4. The 5% liver extract in the duodenum stimulated an increase in gastric acid output amounting to about 40% of the maximum response to histamine. Serum gastrin and GIP levels were not affected. Additional fat (0.5-4.0%) or glucose (10-20%) reduced acid secretion under these conditions by between 50 and 80% without affecting serum gastrin concentrations. Significant increases in the concentration of GIP in the serum occurred in response to intraduodenal glucose (5%), and to fat at the highest dose used (4%). 5. Intraduodenal infusions of glucose (5-20%) significantly increased serum GIP levels. Gastric secretion in response to 5% liver extract in the stomach was significantly inhibited at the highest dose (10 or 20%) although gastrin release was unaffected. 6. These results show that intraduodenal fat and glucose both exhibit potent inhibitory effects on post-prandial gastric acid secretion but that there is no correlation between the changes in serum GIP concentration and the inhibition of gastric secretion under these conditions. 7. We conclude that GIP is unlikely to mediate fat-induced inhibition of gastric secretion, but it is still possible that it might be involved in the inhibition that occurs during intestinal perfusion with hypertonic glucose solutions.

Animals↗
PubMed1983

GIP and insulin responses to a test meal in healthy and obese subjects.

Twenty-three obese and 17 control subjects were studied after ingestion of a heavy breakfast. Blood samples were drawn before and at 30, 60, 90, 120, 150, and 180 min after the start of the meal. The m ean serum insulin level was significantly (p less than 0.02) higher in the obese than in the control group throughout the study, whereas the mean blood glucose concentration was significantly (p less than 0.02) higher in the obese group at 30, 60, and 90 min only. No significant differences between the two groups were noted in fasting or in postprandial plasma GIP, and it appears that hypersecretion of GIP is not responsible for the hyperinsulinemia seen in obesity.

Adult↗
PubMed1983

Disturbances of the entero-insular axis.

The entero-insular axis comprises direct substrate stimulation of the islet cells by the absorbed nutrients and signal transmission by endocrine factors and nerves. The extent of neural influences has not yet been evaluated. GIP is the main incretin candidate. GIP release is dependent on nutrient absorption. Therefore, GIP abnormalities occur in a large number of gastrointestinal and metabolic diseases. These secondary changes are rarely of clinical significance. GIP hypersecretion may, however, contribute to the increased lipogenesis in obesity and the hypoglycemia in the late dumping syndrome. In type II diabetes hyper- and hyposecretion of GIP has been found but no correlation between GIP and insulin response. GIP abnormalities are not identical with disturbances of the entero-insular axis. These can only be evaluated by estimating the incretin effect (comparing the insulin response to oral glucose with the insulin response to an isoglycaemic iv glucose infusion). A decreased incretin effect has been observed in patients with jejuno-ileal bypass and in type II diabetes. In neither condition was a correlation found between incretin effect and GIP response. It is concluded that disturbances of the entero-insular axis are rarely explained by GIP abnormalities. Therefore, other humoral gut factors must exist. Also the neural part of the entero-insular axis requires exploration in health and disease.

Animals↗