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Biomedical subjects

R Kiekens

Publications and source records attributed to R Kiekens.

At least 19 recordsLinked to original sources
PubMed1996

Effects of chronically elevated glucose levels on the functional properties of rat pancreatic beta-cells.

This study examines the effects of chronically elevated glucose levels on the survival and function of purified rat beta-cells. Prolonged exposure (9 days) of beta-cell aggregates to 20 mmol/l glucose did not lead to cell losses, but reduced the amount of insulin secreted in response to glucose. This decrease was not caused by cellular desensitization but resulted from the lower cellular insulin content after a prolonged imbalance between stimulated rates of insulin synthesis and release. Virtually all beta-cells exhibited a state of metabolic and biosynthetic activation, which was maintained for at least 2 h in glucose-depleted media. Their rates of protein and insulin synthesis were amplified by glucose, reaching (half-) maximal stimulation at lower glucose concentrations (2 and 5 mmol/l, respectively) than control cells cultured at 10 mmol/l glucose (5 and 10 mmol/l, respectively). As for insulin release, the net glucose effect on insulin synthesis was markedly reduced as compared with that in control cells. This was also the case after culture at 6 mmol/l glucose. In the latter condition, the lower glucose-inducible activities were caused by cellular desensitization, with 50% of the beta-cells unresponsive to glucose and the other 50% responding with a lower sensitivity (half-maximal stimulation at 7 mmol/l glucose). Comparison of beta-cells cultured at the three glucose concentrations indicated that prolonged exposure to elevated glucose levels increases the number of degranulated cells, of cells with a high proportion of immature insulin granules, and of cells with glycogen deposition-morphologic features previously described in conditions of hyperglycemia. It is concluded that chronic exposure (9 days) of rat beta-cells to elevated glucose levels induces a prolonged state of beta-cell activation and glucose hypersensitivity rather than a glucotoxicity or glucose desensitization. This shift in the functional state of the beta-cell population is responsible for a reduced insulin release in response to glucose, as observed in other conditions of prolonged exposure to high glucose levels.

Animals↗
PubMed1994

Amino-acid responsiveness in beta cell subpopulations with different sensitivity to glucose.

Isolated rat beta-cells differ in their individual responsiveness to glucose. The present study examines whether two beta-cell subpopulations with different thresholds for glucose stimulation also differ in their responsiveness to amino acids that are known to stimulate insulin release. The subpopulations were separated by autofluorescence-activated cell sorting using their metabolic responsiveness to 7.5 mM glucose as discriminating parameter. The 7.5 mM glucose responsive and unresponsive subpopulations were perifused in parallel in order to compare their secretory responses to leucine (10 mM) or to arginine (5 mM); responses to glucose were taken as control. Under maximal glucose stimulation (20 mM), the responsive subpopulation released two-fold more insulin than the unresponsive one whereas maximal stimulation with leucine (10 mM) elicited similar first and second phase responses in the two subpopulations. On the other hand, a maximal arginine stimulus (5 mM) amplified release only from glucose-activated beta-cells; neither did it correct the differences in glucose-induced insulin release between both subpopulations. These results indicate that rat beta-cells exhibit a heterogeneity in secretory responsiveness to glucose but not to leucine, a metabolized secretagogue which can induce release in the absence of glucose. A heterogeneity is also observed in the cellular responsiveness to arginine, and its secretory effect consists of an amplification of glucose-activated cells.

Amino Acids↗
PubMed1994

Physiologic relevance of heterogeneity in the pancreatic beta-cell population.

In vitro studies on purified rat beta cells have indicated a functional diversity among insulin-containing cells. Intercellular differences were found in the rates of glucose-induced insulin synthesis and release. They are attributed to differences in cellular thresholds for glucose utilization and oxidation, as can be caused by varying activities in rate limiting steps such as glucokinase-dependent phosphorylation. The percent of functionally active beta cells increases dose-dependently with the glucose concentration, making cellular heterogeneity and its regulation by glucose major determinants for the dose-response curves of the total beta-cell population. Beta cells which are already responsive to low glucose concentrations are characterized by a higher content in pale immature granules; their activated biosynthetic and secretory activity accounts for preferential release of newly-formed hormone by the total beta-cell population. At any glucose level, the amplitude of insulin release depends on the percent glucose-activated cells and their cyclic AMP content, an integrator of (neuro)hormonal influences. The in vitro described heterogeneity in beta-cell functions may bear physiological relevance as several of its characteristics are also detectable in intact pancreatic tissue; furthermore, in vitro signs of heterogeneity can be altered by prior in vivo treatment indicating that they express properties of the cells in their in situ configuration. Elevated basal levels of (pro)insulin may reflect the existence of an increased number of beta cells that are activated at low physiologic glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Pancreatic beta cell heterogeneity in glucose-induced insulin secretion.

Rat pancreatic beta cells differ in their individual sensitivity to glucose-inducible metabolic changes. The present study examines whether beta cells with a higher metabolic threshold require higher glucose levels for stimulation of their secretory activity. Purified beta cells were distributed according to their metabolic redox state at 7.5 mM glucose; the metabolically responsive (high responsive) and unresponsive (low responsive) subpopulations of comparable size and viability were reaggregated in the presence of [3H]tyrosine and then perfused at 2.8 mM glucose with 10-min pulses of increasing glucose concentration. Glucose elicited first-phase insulin release in both high and low responsive subpopulations from, respectively, 4.2 and 8.3 mM on. The amplitude of both secretory responses increased dose dependently, the rates in the high responsive subpopulation being 2-fold higher than in the low responsive one. At all stimulating glucose levels, fractional release of 3H-labeled insulin was 3- to 4-fold higher than that of immunoreactive insulin. Preferential release of newly formed insulin was already maximally stimulated at 4.2 mM glucose in the high responsive subpopulation, whereas it increased dose-dependently in the low responsive one. These results indicate the existence of intercellular differences in the secretory activity of glucose-exposed beta cells, both in terms of glucose sensitivity and of amplitude. This heterogeneity in beta cell secretory responsiveness parallels that which has been previously described for the cellular metabolic and biosynthetic functions. It is concluded that glucose dose-dependently recruits beta cells into both biosynthetic and secretory activities. Co-existence of inactive and activated cells can explain preferential release of newly synthesized over preformed hormone during glucose stimulation.

Animals↗
PubMed1992

Differences in glucose recognition by individual rat pancreatic B cells are associated with intercellular differences in glucose-induced biosynthetic activity.

In vitro incubated rat islet B cells differ in their individual rates of protein synthesis. The number of cells in biosynthetic activity increases with the glucose concentration. Flow cytometric monitoring of the cellular redox states indicated that islet B cells differ in their individual metabolic responsiveness to glucose. A shift from basal to increased NAD(P)H fluorescence occurred for 18% of the cells at 1 mM glucose, for 43% at 5 mM, and for 70% at 20 mM. The functional significance of this metabolic heterogeneity was assessed by comparing protein synthesis in metabolically responsive and unresponsive subpopulations, shortly after their separation by autofluorescence-activated cell sorting. The glucose-sensitive subpopulation exhibited four- to fivefold higher rates of insulin synthesis during 60-min incubations at 2.5-10 mM glucose. Its higher biosynthetic activity was mainly caused by recruitment of cells into active synthesis and, to a lesser extent, by higher biosynthetic activity per recruited cell. Cells from the glucose-sensitive subpopulation were larger, and presented a threefold higher density of a pale secretory vesicle subtype, which is thought to contain unprocessed proinsulin. It is concluded that intercellular differences in metabolic responsiveness result in functional heterogeneity of the pancreatic B cell population.

Animals↗
PubMed1991

Measuring the balance between insulin synthesis and insulin release.

The absolute rates of hormone synthesis and release were determined in purified pancreatic B cells. Newly synthesized proteins were labeled with L-[3,5-3H]tyrosine or L-[2,5-3H]histidine. When medium glucose was less than or equal to 10 mM, the production of insulin exceeded or equaled its release. Raising the glucose levels above 10 mM did not further increase the rate of insulin synthesis (67 +/- 10 fmol/10(3) cells/2 hour) but elevated that of insulin release up to 3-fold the production rates (181 +/- 10 fmol/10(3) cells/2 hour). In the presence of glucagon or of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate the cells also released 3-fold more hormone that they synthesized; release was however reduced to 25% of the rate of production in the presence of epinephrine. It is concluded that glucose as well as hormonal regulators of islet B cells can influence, bi-directionally, the balance between the rates of insulin synthesis and release.

Animals↗
PubMed1985

Nonparallelism of digestive enzymes in rat pancreatic hypersecretion.

During a 4 days' cannulation of the pancreatic duct in conscious rats, pancreatic hypersecretion developed. The enzymic composition of the juice altered with time. Amylase secretion reached a plateau after 24 h, whereas the lipase secretion continued to increase for 48 h. The mean trypsinogen and chymotrypsinogen output was three times greater on the 4th day than during the first 24 h. The intrapancreatic content of the enzymes diminished with a different disappearance rate for each enzyme. After 96 h the pancreas contained only 15% of the initial amounts of amylase; lipase also decreased to 15%, chymotrypsinogen to 32% and trypsinogen to 42% of the basal value. Comparison of the rates of synthesis of enzymes on the 1st and the 4th days of study showed an increase of 89% for amylase, 291% for trypsinogen, 300% for chymotrypsinogen and 759% for lipase. It is concluded that the nonparallel content and secretion of digestive enzymes during the course of several days pancreatic hypersecretion is due to different synthesis rates for each enzyme.

Amylases↗
PubMed1983

[Surgery of acute cholecystitis in patients 80 years of age or older].

In 17 Belgian surgical centers, 324 operations have been performed for acute cholecystitis in patients 80 years of age or older. In this group of patients: 1. The incidence of acute cholecystitis is hardly higher in women than in men. 2. The patients were operated within 24 hours of admission in 38% of cases. The main bile duct was surgically explored in 1/3 of patients. Cholecystostomy or simple drainage were used in 1/10 of cases only. 3. Operative mortality was 19%. It was higher for patients operated as emergencies than for delayed operations and higher also when the cholecystectomy was associated with an exploration of the bile duct. The ideal treatment for such patients should thus be a cholecystectomy with an endoscopic sphincterotomy.

Acute Disease↗
PubMed1983

[Surgery in the octogenarian (introduction). Results of a national survey].

Presentation of the results of a national, multicentric and retrospective study regarding the surgery of the octogenarian. The series counts 7,407 patients accepted for surgery, and which can be divided into 4,581 women (61.8%) and 2,826 men (38.2%) of an average age of 84.4 years old (extremities 80-101 years old). The global mortality of this population of elderly (whether operated on or not) amounts to 16.7%. The postoperative mortality of the 4,177 operated patients is 18.2% with different rates according to the surgical disciplines: 34.7% for surgery of the colon, 23.2% for bone surgery, 22.4% for vascular surgery, 15.3% for biliary surgery, 8.7% for urologic surgery and 5.6% for cardiac surgery.

Age Factors↗
PubMed1980

[Valvulography for the evaluation of the cerebrospinal shunt in childhood hydrocephalus (author's transl)].

Infection and obstruction of the cerebrospinal shunt are the most important disturbances in the management of childhood hydrocephalus. Often an occlusion of the shunt cannot be localized by conventional diagnostic means. Therefore the patency of Heyer-Systems was studied in 28 hydrocephalic children aged 2 months to 15 years with clinical signs of an increased intracranical pressure. The so-called valvulography with 99mTc-pertechnetate or Metrizamide (Amipaque). In more than 96% the results were confirmed during operation. The advantages of the X-ray method are: instrument and contrast medium are available at any time and the combination with cranial computertomography gives more precise data than scintigraphy alone.

Adolescent↗
PubMed1980

[Perforating stomach ulcer in newborns].

Acute peptic ulceration of the stomach and duodenum is rare in children. The surgical treatment in the event of complications should be kept as simple as possible and there is usually no ulcer diathesis present. The significance of the pneumoperitoneum without visceral rupture is stressed. The gastrographin meal should be considered if ulcer perforation is suspected.

Diagnosis, Differential↗
PubMed1979

Non-parallel secretion of pancreatic enzymes. Effect of parenteral amino acid administration and intestinal reinfusion of bilio-pancreatic juice.

Chronic drainage of pancreatic juice in rats results in a non-parallel secretion of digestive enzymes. The concentration of trypsinogen, chymotrypsinogen, procarboxypeptidase B and lipase increases continuously whereas that of amylase drops. An amino acid mixture given intravenously does not affect this dissociation. Reinfusion of bilio-pancreatic juice into the duodenum on the contrary influences the relative enzyme release: the increase in concentration of the three proteolytic enzymes and of lipase is less pronounced over the 72-hour study period; amylase concentration remains unaffected. In the absence of an intravenous amino acid feeding the pancreatic protein output is more than halved and a negative nitrogen balance is observed. Reinfusion of bilio-pancreatic juice does not alter the total protein output. This report confirms the persistance of a dissociation in the rate of enzyme release in rats with chronic pancreatic fistula despite sufficient protein administration and intestinal reintroduction of bilio-pancreatic juice.

Amino Acids↗
PubMed1976

[Ulcer of the colon and Mallory-Weiss syndrome (author's transl)].

A 71 year old man presents with a high and low hemorrhage with no signs of associated shock. Endoscopy shows a laceration of the cardia (Mallory-Weiss syndrome). The low hemorrhage is attributed to a left colic lesion that appears to be an ischemic colitis. Colonoscopy in addition to baryum enema is useful in the differential diagnosis of colon lesions.

Aged↗