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Biomedical subjects

W Kerner

Publications and source records attributed to W Kerner.

At least 55 records · Page 3Linked to original sources

Evidence for effects of insulin on sensory processing in humans.

Systemic insulin passes the blood-brain barrier and insulin receptors have been detected in various brain regions. Yet, the biological significance of insulin acting on the brain remains rather unclear. Reports of different awareness of hypoglycemic symptoms during hypoglycemia induced by human insulin (HI) and porcine insulin (PI) suggest a modulatory influence of insulin on sensory processing. In a double-blind, within-subject, crossover comparison, we recorded visual-evoked potentials (VEP) in 30 healthy men during euglycemia and after 20 or 50 min of constant hypoglycemia of 2.66 mM (47.9 mg/dl) induced by HI and PI. Blood glucose and serum insulin levels were identical in both sessions. Hypoglycemia reduced amplitudes of the VEP components P1 and N2 and increased latencies of N1, P1, and N2. However, hypoglycemia-induced changes in VEP amplitudes and latencies were significantly stronger during PI and HI infusion: P1-N2 difference amplitude decreased from (mean +/- SE) 11.9 +/- 0.9 to 10.7 +/- 0.8 muV during HI and from 12.4 +/- 0.9 to 8.7 +/- 0.7 muV during PI infusion (P < 0.002). P1 latency increased from 112.0 +/- 3.2 to 118.8 +/- 3.2 ms during HI and from 114.0 +/- 3.3 to 126.3 +/- 4.6 ms during PI infusion (P < 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, which indicates a short-term action of the hormone. The results add to those of a foregoing study demonstrating differential effects of HI- and PI-induced hypoglycemia on auditory evoked potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Classically conditioned changes of blood glucose level in humans.

Procedures of classical conditioning in animals and man have provided evidence that most psychophysiological responses can be acquired by repeated association with previous neutral stimuli. Many animal studies reported on conditioned changes in the blood glucose level; the nature of the conditioned response (CR), hypo- or hyperglycemia, however, seems to vary with experimental procedures. The present study aimed to elicit conditioned blood glucose changes in human subjects. Thirty male volunteers participated in five sessions each. The sessions were separated by 3 days, with identical time course and procedure. The subjects were informed that we wanted to test the effects of insulin or placebo injections on cognitive functioning, and were kept busy with pseudotests. In four sessions, subjects were injected with 0.035 IU/kg body weight of human insulin as the unconditioned stimulus (US), which induced the expected fall in blood glucose level below 50 mg/dl (UR). Injections were accompanied by a specific stimulus compound (conditioned stimulus, CS) in half of the subjects. In the fifth session, the CS was associated with a placebo injection. About half of the subjects showed a change from the baseline level of blood glucose of more than 10 mg/dl, which we would interpret as a conditioned response. Conditioning occurred more often in those subjects who were given a CS compound in addition to the injection, which itself together with the experimental environment may have been a sufficient CS.

Adult↗

The function of a hydrogen peroxide-detecting electroenzymatic glucose electrode is markedly impaired in human sub-cutaneous tissue and plasma.

Electroenzymatic glucose sensors implanted into sub-cutaneous (s.c.) tissue of human subjects and experimental animals exhibit lower sensitivities to glucose than in buffer solutions before implantation. The mechanism of the decrease of sensitivity is not known. Sensors used in this study were fabricated from platinum wires (diameter 0.125 mm) with covalently bound glucose oxidase at the tip of the wire. After coating the tip with polyurethane, wires were placed into 27 gauge steel needles. Sensors were operated potentiostatically at 700 mV against Ag/AgCl pseudo-reference electrodes. These sensors were implanted s.c. in 6 diabetic patients for 7 h. In 4 patients, sensors were responsive to successive increases of plasma glucose levels. Mean sensitivity to glucose in s.c. tissue was 29% of in vitro sensitivity. In 2 patients there was a sudden decrease of sensor currents, unrelated to glucose, shortly after implantation. Sensors were inhibited in human plasma to a similar extent. When sensors were exposed to native plasma and to plasma ultrafiltrate (mol. wt. < 10 kDa) for 10 h, identical decreases of signals were found. Exposure to dialysed plasma (mol. wt. > 12 kDa) caused much less decrease of sensor signals. Losses of sensor sensitivities to glucose in s.c. tissue and in plasma were totally reversible upon re-exposure of sensors to buffer solutions. We conclude that sensor inactivation in plasma and possibly in s.c. tissue is caused by low molecular weight substances not retained by the polyurethane membrane.

Adult↗

On line continuous monitoring of subcutaneous tissue glucose is feasible by combining portable glucosensor with microdialysis.

A new method for continuous measurement of subcutaneous tissue glucose content is introduced: by combining the microdialysis technique with a wearable amperometric glucose sensor, a device for continuous glucose measurement in the subcutaneous tissue was obtained. This device was applied to healthy volunteers (n = 10) over the period of an oral glucose load and to type I diabetic patients (n = 10) under the conditions of daily life. Glucose profiles in both healthy and diabetic persons were followed in the subcutaneous tissue up to 27 hours. This technique will certainly open new perspectives of monitoring and treating diabetic patients.

Biosensing Techniques↗

Combination of microdialysis and glucosensor permits continuous (on line) SC glucose monitoring in a patient operated device. II. Evaluation in animals.

The microdialysis technique was used for following the glucose content of the extracellular subcutaneous (SC) fluid under varying blood glucose levels in rats. The glucose content in the microdialysis perfusion fluid was continuously analyzed by means of the measuring flow chamber of an ex vivo glucose monitor. In six ChBB rats blood glucose levels were varied between 40 mg/dl and 575 mg/dl by intravenous (IV) infusion of glucose and by SC injections of insulin, respectively. After a running-in period of about half an hour, the glucose content in the perfusion fluid was closely related to the blood glucose concentration (r > 0.92) up to a time period of 6 hrs. The "relative recovery" rate of glucose by the microdialysis probe in the SC tissue varied within the 6 experimental sessions. The relative recovery rate could be shown to be not dependent on the absolute blood glucose levels in the individual rat within the glucose concentration range tested.

Animals↗

Combination of microdialysis and Glucosensor permits continuous (on line) s.c. glucose monitoring in a patient operated device: I. In vitro evaluation.

A device for continuous glucose monitoring in fluids was obtained by combining the microdialysis technique with a measuring flow chamber of the "Glucosensor Unitec Ulm" using the GOD method for determining amperometrically blood glucose profiles. The in vitro experiments demonstrate that the relative recovery of glucose by this device is inversely related to the flow rate of the microdialysis perfusion fluid, which, in turn, is inversely related to the response time of the device. The glucose signal increases linearly with the area of the microdialysis working membrane (r = 0.98), and with the glucose concentrations of the standard solutions (r greater than 0.95). The variation coefficient for repeated measurements is below 8%. The accuracy of the device as demonstrated by mean measuring deviation ranges between 1 and 3.8%.

Biosensing Techniques↗

Hepatic sulfhydryl content under adrenergic stimulation in male rats.

The influence of a series of sympathomimetic agents on the liver content of non protein bound thiol groups (NP-SH), mainly representing glutathione, has been assessed in the male rat. The rats were intravenously and/or subcutaneously infused over 6 h at different dosages either with dopamine, dobutamine, epinephrine, terbutaline, or phentolamine, or simultaneously with dopamine and phentolamine, or with epinephrine and phentolamine. Besides NP-SH, total sulfhydryl group content was measured in liver cytosol, while glucose and insulin concentrations were determined in the serum. Liver NP-SH content was significantly decreased by epinephrine. This decrease was abolished and even inverted to an increase, when appropriate doses of phentolamine were infused simultaneously. Dopamine caused a rise in NP-SH content at a dose rate of 7.5 micrograms/kg.min, while lower and higher dose rates of dopamine exerted not any influence on liver NP-SH. When phentolamine was concomitantly infused with 15 micrograms/kg.min of dopamine, NP-SH was significantly elevated. Phentolamine, when infused exclusively, increased NP-SH as well, while it was not influenced, however, by terbutaline or dobutamine at any dosage. Cytosolic total sulfhydryls were found to be unaltered across all experimental groups. When the NP-SH values are related to the corresponding serum insulin levels, a close and linear relationship becomes evident. The study demonstrates, that some sympathomimetic agents can exert a considerable influence on hepatic non protein bound thiol content. The data suggest, that the varying liver NP-SH content under adrenergic drugs is primarily related to changes in serum insulin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Progress in practical endocrinology. The Glucosensor Unitec Ulm--a portable monitor for continuous blood glucose measurement.

The Glucosensor Unitec Ulm is the first portable glucose sensor for continuous glucose monitoring in blood. The Glucosensor weighs 850 g and has a size of 15 x 19 x 7 cm. Over a 24 hr period 15-25 ml of blood are withdrawn for continuous measurement, depending on the pumping velocity. Its storing capacity for data of blood glucose readings amounts to 32 KB. With the Glucosensor "long-term glucograms" under near-normal conditions can be registered. The glucograms enable the physician to recognize the different deteriorations of glucose met- abolism eg. periods of silent hypoglycemia during the night as well as postprandial hyperglycemia. The degree of glycemic control of diabetic patients can be analyzed and the effect of blood glucose lowering therapeutics can be realistically assessed.

Blood Glucose↗

Differential effects of human and pork insulin-induced hypoglycemia on neuronal functions in humans.

Insulin has been found to cross the blood-brain barrier, and insulin receptors have been detected in different structures of the brain. However, the biological significance of insulin acting in the brain remains unclear. Reports of differential awareness of hypoglycemic symptoms during human insulin (HI)- and pork insulin (PI)-induced hypoglycemia hint at a modulatory influence of insulin on sensory processing. In a double-blind study, we recorded auditory-evoked potentials (AEPs), indexing neuronal transmission along sensory pathways, in 30 healthy male subjects during a baseline condition and HI- and PI-induced mild hypoglycemia of 2.65 mM. Fifteen subjects were tested after 20 min and another 15 after 50 min of constant hypoglycemia. During hypoglycemia, subjects had to indicate the severity of hypoglycemic symptoms and their current mood. Hypoglycemia increased latencies of the P3 component and reduced amplitudes of the N1, P2, and P3 components. Despite identical blood glucose and serum insulin levels in both sessions, effects of PI-induced hypoglycemia on AEP components were significantly stronger than those of HI-induced hypoglycemia (P less than 0.05). Differences between the effects of the insulins were consistently apparent after 20 min of hypoglycemia, indicating a short-term action of these hormones on central nervous system functions. Also, after 20 min, but not after 50 min, of steady-state hypoglycemia, subjects felt more excited during PI than HI infusion (P less than 0.05). The results indicate different influences of HI and PI on sensory function during hypoglycemia. These differences, occurring during early hypoglycemia, could contribute to the differential awareness of hypoglycemic warning symptoms during HI- and PI-induced hypoglycemia in diabetic patients.

Animals↗

Different effects of human and porcine insulin on hypoglycemia-induced abnormalities of brainstem sensory function.

Following a switch from porcine insulin (PI) to human insulin (HI), a subgroup of diabetic patients complained of unawareness of hypoglycemia. In the present study, a glucose clamp technique was used to assess changes in auditory evoked brainstem responses (ABR) during infusion of HI and PI (0.015 IU/kg/min) under conditions of euglycemia (about 5.00 mM) and of hypoglycemia (3.40 and 2.60 mM) in 9 healthy volunteers. Serum insulin and plasma glucose did not differ between HI and PI conditions. ABR components remained unchanged during the euglycemic clamp, but increased in latency during hypoglycemia in all subjects. At mean glucose levels of 2.60 mM, the increase in latency of ABR wave V ranged between 50 and 400 microseconds during PI infusion, and between 100 and 2,460 microseconds during HI infusion. Thus, compared to the PI condition, changes during HI infusion were significantly more variable (p less than 0.01) due to some subjects displaying extremely prolonged ABR latencies. These findings suggest that hypoglycemia induced by HI can be more detrimental to early sensory processing in humans as compared to PI.

Adult↗

[Effect of pancreatin on diabetes mellitus in chronic pancreatitis].

The effect of pancreatin on insulinopenic diabetes was studied in 10 patients with chronic pancreatitis and exocrine function impairment. All patients were treated for 4 days in a randomized crossover trial with either pancreatin (6 x 2 capsules, 6 x 300 mg/d) or placebo. Blood glucose levels were determined 7 times every day and night. On day 5, the patients were studied by a glucose sensor with adjustment of blood glucose to 120 mg/dl until 8.00 in the morning. A test meal was applied with 2 capsules pancreatin or placebo. Blood glucose and plasma levels of C-peptide, glucagon and pancreatic polypeptide (PP) were determined in regular intervals for 4 hours. Blood glucose levels were not significantly altered by pancreatin. As shown by M-value according to Schlichtkrull (21.6 +/- 2.9 versus 32.4 +/- 7.4), there was a tendency towards smaller oscillations of blood glucose with pancreatin treatment. C-peptide levels (basal 0.081 +/- 0.008 ng/ml; postprandial 0.119 +/- 0.013 ng/ml) were not significantly altered by the administration of pancreatin. Basal and postprandial glucagon and PP plasma levels were not influenced by pancreatin. From these results, we conclude that pancreatic enzyme supplementation does not significantly alter the requirement of insulin in patients with diabetes mellitus secondary to chronic pancreatitis. Possible disturbances of the enteroinsular axis are discussed in this paper.

Blood Glucose↗