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Biomedical subjects

K Hermansen

Publications and source records attributed to K Hermansen.

At least 109 records · Page 6Linked to original sources
PubMed1987

Diurnal plasma profiles of metabolite and hormone concentration in insulin-dependent diabetic patients during conventional insulin treatment and continuous subcutaneous insulin infusion. A controlled study.

In addition to hyperglycaemia, derangement of metabolic and hormonal control may play an important role in the development of microvascular complications in diabetes. Little, however, is known about the impact of insulin pump treatment on metabolic and hormonal parameters. In a 6-month prospective randomized study in insulin-dependent diabetics we therefore investigated the effects of continuous subcutaneous insulin infusion by pump (10 patients) and conventional insulin treatment (10 patients) on the 24-h profiles of blood glucose, glycerol, lactate, 3-hydroxybutyrate, insulin, glucagon and growth hormone by measuring the respective concentrations every 2 h. We found that average blood glucose levels and HbA1c were significantly lower in the group treated by continuous subcutaneous insulin infusion as compared with the group on conventional insulin treatment. Furthermore, we observed an improvement in diurnal levels of lactate and 3-hydroxybutyrate in the pump-treated group which was not seen in the conventionally treated group. A slight increment in alanine was seen in the group treated with insulin pump. Serum growth hormone, glycerol, plasma free insulin as well as the daily insulin supply were unchanged and identical in the two groups. It is noteworthy that in the pump group, the decrease in blood glucose and 3-hydroxybutyrate takes place concomitantly with a significant suppression of glucagon.

3-Hydroxybutyric Acid↗
PubMed1987

Characterization of growth hormone-releasing hormone stimulation of the endocrine pancreas: studies with alpha- and beta-adrenergic and cholinergic antagonists.

The 40 aminoacids residue of pancreatic growth hormone-releasing hormone stimulates the secretion of insulin, glucagon, an somatostatin from the pancreas. To determine whether this stimulation of islet hormone secretion is mediated via adrenergic or cholinergic receptor sites, we studied the effects of 30 nmol/l of the growth hormone-releasing hormone on the release of insulin, glucagon, and somatostatin in the presence of either alpha-adrenergic (phentolamine), beta-adrenergic (propranolol) or cholinergic (atropine) blocking agents. The responses to the growth hormone-releasing hormone were not significantly modified by adrenergic or cholinergic blockers. The findings rule out an interaction with adrenergic and cholinergic receptors on islet cells. It is at present unknown whether the growth hormone-releasing hormone stimulates islet hormone secretion via an interaction with specific growth hormone-releasing hormone receptors or vasoactive intestinal peptide receptors.

Animals↗
PubMed1986

Differential glycaemic effects of potato, rice and spaghetti in type 1 (insulin-dependent) diabetic patients at constant insulinaemia.

The blood glucose responses to cooked potato, rice and spaghetti were studied in six Type 1 (insulin-dependent) diabetic patients who had attained euglycaemia by the artificial pancreas prior to the meal intake. The amount of potato (raw weight 200 g), parboiled rice (raw weight 50 g), and spaghetti (raw weight 50 g) had approximately identical caloric content (range 203-225 kcal) and amount of available carbohydrate (range 39.4-43.4 g). The postprandial blood glucose response areas after cooked potato and cooked parboiled rice were similar (180 min values: cooked potato: 1190 +/- 110 mmol/l X min, cooked rice: 1160 +/- 140 mmol/l X min and 240 min values: cooked potato: 1690 +/- 140 mmol/l X min, cooked rice: 1740 +/- 210 mmol/l X min). In contrast, the response after cooked spaghetti was slower and less pronounced (180 min value: 830 +/- 80 mmol/l X min and 240 min value: 1320 +/- 120 mmol/l X min), and was significantly smaller than those of cooked potato (180 min: 2p less than 0.01 and 240 min: 2p less than 0.01) as well as cooked rice (180 min: 2p less than 0.01 and 240 min: 2p less than 0.02). Our study emphasizes the importance of determining the glycaemic response of foodstuffs under conditions of isoinsulinaemia.

Adult↗
PubMed1986

The effect of six months continuous subcutaneous insulin infusion on kidney function and size in insulin-dependent diabetics.

Glomerular filtration rate (GFR), renal plasma flow (RPF), kidney volume, and urinary albumin excretion rate were measured in 24 insulin-dependent diabetics, aged 29 +/- 7 years (mean +/- S.D.) of 8 +/- 4 years duration, randomly allocated to either continuous subcutaneous insulin infusion (CSII) (n = 12) or unchanged conventional insulin treatment (CIT) (n = 12). Glomerular filtration rate, renal plasma flow, and kidney volume were identical in the two groups at the start of the study, although significantly increased above normal values. During the 6 months CSII treatment a reduction of the GFR from 145 +/- 21 to 132 +/- 14 ml/min (2p = 2.4%) was seen, no change was observed in the CIT group while in both groups RPF and kidney volume remained unchanged. Urinary albumin excretion rate was normal or near normal in both groups and remained unchanged. Thus improved glycaemic control in insulin-dependent diabetics studied before the onset of microalbuminuria is associated with improved (reduced) GFR. Nephromegaly does not improve with 6 months CSII treatment. Whether it would improve with more prolonged treatment is uncertain.

Adult↗
PubMed1986

The effect of vitamin E and selenium on doxorubicin (Adriamycin) induced delayed toxicity in mice.

The antagonistic action of repeated administration of vitamin E and selenium on the lethality caused by a single intraperitoneal injection of doxorubicin 15 to 20 mg/kg has been investigated in mice. Mice were treated with vitamin E, 20 to 4100 mg/kg intraperitoneally/intramuscularly daily or once a week and/or selenium 27 micrograms/kg orally daily for 6 to 7 weeks, i.e. one or two weeks before and five weeks after doxorubicin administration. 30 mg/kg of doxorubicin intraperitoneally caused 100% lethality within 4 days, whereas 15 mg/kg caused no deaths within a week, but resulted in a delayed toxicity with a cumulative lethality of 80% at the end of the observation period of 6 months. Vitamin E protected the mice from the lethal effect of doxorubicin, 15 mg/kg during the administration, but the mice began to die when the vitamin E administration was discontinued. Selenium only protected the mice for two weeks in spite of the continuous administration of selenium. The combined administration of vitamin E and selenium had no protective effect on the lethality caused by doxorubicin, 20 mg/kg. The pathogenesis of the delayed lethality of a single doxorubicin administration in mice is discussed. It is concluded that vitamin E and/or selenium have no significant protective action against doxorubicin induced delayed lethality in mice.

Administration, Oral↗
PubMed1986

The pharmacokinetics and protein binding of disopyramide in pigs.

The pharmacokinetics of disopyramide were investigated in 5 pigs. Disopyramide was administered as intravenous bolus injections at different doses and as intravenous infusions at different rates. By measuring the free and total concentrations in plasma of parent compound and desisopropyldisopyramide (the main metabolite in humans) and the amounts excreted in urine it was found that disopyramide had a concentration dependent protein binding and that free and total concentrations could be described by a two-compartment model with a t1/2, beta of approximately 2 hours. The free concentrations were found to be more valuable for estimating the kinetic parameters. The total clearance of disopyramide in the pig was found to approximately 3 ml/min./kg which is about 3 times greater than in man. In contrast to humans the free clearance in the pig increased with declining concentration. Apart from this the kinetics of disopyramide in the pig were very similar to those in man. In conclusion the pig could be a relevant model for studying the pharmacokinetics in humans.

Animals↗
PubMed1986

The analgesic effect of buprenorphine, etorphine and pethidine in the pig: a randomized double blind cross-over study.

In order to find a suitable analgesic for the treatment of postoperative pain in pigs the analgesic effect of buprenorphine, etorphine and pethidine has been compared in 8 domestic pigs. For assessment of the analgesic action on thermal (hot plate) and two mechanical (cannulation of ear vein, needle prick) noxious stimuli have been employed. In a pilot experiment on 2 pigs in which methadone was included the maximal effective doses were estimated for each drug. Methadone was found unsuitable because of unacceptable side effects (respiratory dysfunction, hyperactivity) at effective dose levels. Next buprenorphine 120 micrograms/kg, etorphine 3 micrograms/kg and pethidine 20 mg/kg all given intramuscularly were compared in a randomized blind trial with a balanced cross-over design on 6 pigs. Etorphine proved to have the highest and pethidine the lowest maximal analgesic effect which was especially evident in the needle-prick test. Buprenorphine proved to have the longest duration of action in all three analgesic tests, in the hot plate test lasting between 7 and 24 hrs. Etorphine had a duration of 3 to 5 hrs whereas the effect of pethidine was short, only lasting about 2 hrs. Etorphine provides a complete analgesia but has a small safety margin for which reason it should be used with caution in the pig. The experimental results indicate that buprenorphine should be the first drug of choice in the treatment of pain after surgical intervention due to its long duration of action and lack of side effects.

Analgesia↗
PubMed1986

Synthetic pancreatic growth hormone-releasing factor (GRF-40) stimulates the secretion of the endocrine pancreas.

The effects on islet hormone secretion of the synthetic replicates of two peptides with potent GH-releasing activity isolated from human pancreatic islet cell tumors (GRF-40 and GRF-44) were studied using the isolated, perfused dog pancreas. GRF-40 produced a dose-dependent stimulation of insulin, glucagon, and somatostatin secretion. The responses to GRF-40 were modified by the prevailing glucose level: higher insulin and somatostatin and lower glucagon responses were obtained at high rather than low glucose. In contrast, GRF-44 did not produce any stimulation of the endocrine pancreas. In vivo GRF-40 and GRF-44 elicited identical pronounced growth hormone responses in the rat. The findings reported here provide support that pancreatic insulin and glucagon are modulated by GRF-40 with somatostatin as its inhibitory counterpart. The question, whether GRF-40 is of physiologic relevance in the regulation of the endocrine pancreas, must await evidence that it is present and releasable from the pancreas.

Animals↗
PubMed1986

Enhancement of glomerular filtration rate and renal plasma flow by oral glucose load in well controlled insulin-dependent diabetics.

Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in 27 patients with uncomplicated insulin-dependent diabetes (IDDM) before and after an oral glucose load of 1.1 g glucose/kg body wt. In the 18 patients showing near-normoglycaemia (blood glucose less than or equal to 8 mmol/l) before the glucose challenge the increase in blood glucose from 4.2 +/- 1.7 to 15.2 +/- 2.3 mmol/l was accompanied by an enhancement of GFR from 128 +/- 15 to 132 +/- 14 ml/min X 1.73 m2 (2p = 0.030) and of RPF from 534 +/- 116 to 562 +/- 105 ml/min X 1.73 m2 (2p = 0.023). By contrast oral glucose load to the nine patients with hyperglycaemia (greater than 8 mmol/l) during baseline conditions raising blood glucose from 11.9 +/- 2.0 to 19.6 +/- 1.5 mmol/l was accompanied by a reduction in GFR from 149 +/- 15 to 139 +/- 9 ml/min X 1.73 m2 (2p less than 0.001) while RPF was unchanged. No changes in blood pressure or urinary albumin excretion rates took place in either group. The reduction in plasma protein and in plasma growth hormone concentration were similar in the two groups. No change was seen in plasma arginine vasopressin concentration. There was no difference in the qualitative GFR response in patients with high initial GFR values (greater than or equal to 130 ml/min X 1.73 m2) as compared to patients with initial values below 130 ml/min X 1.73 m2. It is concluded that the induction of moderate hyperglycaemia in IDDM patients is followed by an enhancement of GFR and RPF-provided near-normoglycaemia before the glucose challenge.

Administration, Oral↗
PubMed1986

Lipoprotein changes during continuous subcutaneous insulin infusion in insulin-dependent diabetic patients.

We have studied the long-term effects (9 months) in plasma lipoprotein concentrations during continuous subcutaneous insulin infusion (CSII) (n = 11, six females, five males) and compared these changes to conventional insulin therapy (CIT) (n = 12, six females, six males). The two groups were allocated to CSII or CIT randomly, and were comparable as regards lipoprotein values at the start of the study. There were initially normal total plasma cholesterol values in both groups (CSII group: mean plasma cholesterol 3.77 +/- 0.57 mmol/l, CIT group: mean plasma cholesterol 4.37 +/- 0.55 mmol/l, means +/- SD). Further, there were normal total plasma triglyceride values at the start of the study (CSII group: mean plasma triglyceride 0.86 +/- 0.23 mmol/l, CIT group: mean plasma triglyceride 0.84 +/- 0.26 mmol/l, means +/- SD). There were no alterations seen in total plasma cholesterol and total plasma triglyceride in either groups during a 9 months observation period. In the same period no changes in LDL and HDL levels were registered. The very low density lipoprotein (VLDL) was separated into VLDL-1 and VLDL-2 by its binding to heparin-sepharose columns. It was found that CSII treatment for 9 months resulted in a decline in VLDL-2-triglyceride values (0.18 +/- 0.07 mmol/l before versus 0.10 +/- 0.07 mmol/l after, p less than 0.05, means +/- SD) which was not seen in the CIT group. Decline in VLDL-2-triglyceride might delay the development of late diabetic manifestations.

Adult↗
PubMed1986

Exercise capacity and cardiac function in type 1 diabetic patients treated with continuous subcutaneous insulin infusion. A controlled study.

In order to investigate the effect of improved glycaemic control on exercise capacity and cardiac function, bicycle exercise and echocardiography at rest and after exercise was performed in 24 short-term type 1 diabetic patients, randomized to conventional insulin therapy (CIT) or to continuous subcutaneous insulin infusion (CSII). After 6 months significant improvement in glycaemic control was seen in the CSII group showing a decrease in mean blood glucose and haemoglobin A1c (HbA1c), while no change was observed in the CIT group. Exercise capacity increased by 24% (p less than 0.01) in the CSII group and decreased by 16% (NS) in the CIT group. In the CSII group fractional shortening of the left ventricle during rest decreased by 14% (p less than 0.02), while an increase of 2% (NS) was seen in the CIT group. Further, changes of left ventricular fractional shortening during rest were inversely correlated to changes in exercise capacity. After exercise, fractional shortening of the left ventricle and rate-pressure product was unchanged in the two groups. In conclusion this study shows a beneficial effect of improved glycaemic control induced by CSII on exercise capacity possibly by reducing resting state demands to the cardiovascular system.

Adult↗
PubMed1986

Effects of furosemide and indapamide upon pancreatic insulin and somatostatin secretion in vitro.

Antihypertensive treatment with furosemide and indapamide may eventually cause impairment of glucose metabolism. To study if this was due to a direct effect on the endocrine pancreas, we examined the effects of furosemide and indapamide on the release of insulin and somatostatin from the isolated perfused pancreas of normal dogs. Furosemide at concentrations ranging between 1-30 micrograms/ml inhibited insulin in a dose-dependent manner (2p less than 0.01) whereas the somatostatin secretion was left unchanged. Also the infusion of indapamide at doses ranging between 0.05-1 micrograms/ml subdued B-cell secretion at the two highest concentrations of 0.5 (by 15 +/- 2%, p less than 0.01) and 1 microgram/ml (by 22 +/- 5%, p less than 0.02) while pancreatic D-cell secretion did not alter. The results suggest, that furosemide and indapamide possess the ability to directly inhibit insulin secretion. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during therapy remains, however, uncertain.

Animals↗
PubMed1985

Increased myocardial contractility in short-term type 1 diabetic patients: an echocardiographic study.

Cardiac function was investigated by echocardiography in 24 short-term Type 1 diabetic patients with a mean diabetes duration of 7 years (range 4-14 years) during conditions of ordinary metabolic control. Compared to 24 age and sex matched normal control subjects, measurements of myocardial contractility as left ventricular fractional shortening and mean circumferential shortening velocity were increased by 12% and 20% respectively. Another 8 Type 1 diabetic patients were examined during conditions of poor (hyperglycaemia and ketosis) and good metabolic control. Following improved glycaemic control, left ventricular fractional shortening and mean circumferential shortening velocity decreased by 16% and 24% respectively. Our findings show that short-term Type 1 diabetes is associated with increased myocardial contractility. Furthermore, this condition is related to the state of metabolic control.

Adult↗
PubMed1985

Effects of a thiazide diuretic (hydroflumethiazide) and a loop diuretic (bumetanide) on the endocrine pancreas: studies in vitro.

Treatment with thiazide diuretics causes an impairment of the glucose metabolism. To study whether this is due to a direct effect on the endocrine pancreas, the effects of the thiazide hydroflumethiazide on the release of glucagon, insulin, and somatostatin from the isolated perfused pancreas of normal and alloxan diabetic dogs were examined. Hydroflumethiazide at concentrations ranging from 1 to 50 micrograms/mL stimulated the normal secretion of glucagon (P less than 0.001), insulin (P less than 0.001), and somatostatin (P less than 0.001) in a dose-dependent manner. The normal hormone responses evoked by 50 micrograms/mL of the thiazide were, however, modified by the prevailing glucose level: higher insulin (P less than 0.05) and somatostatin (P less than 0.05) and lower glucagon (P less than 0.05) were obtained at the high glucose concentration of 11 mmol/L rather than at the low glucose concentration of 1.3 mmol/L. In alloxan diabetes, insulin secretion was almost extinct and did not respond to hydroflumethiazide, whereas glucagon was dose-dependently stimulated (P less than 0.001). In addition, we looked at the effect of the loop diuretic, bumetanide. The infusion of bumetanide at doses ranging from 0.5 to 3 micrograms/mL did not alter the release of glucagon, insulin, and somatostatin in the presence of 5.5 mmol/L glucose. The results suggest that hydroflumethiazide possesses the ability to directly stimulate A cell secretion in the normal and alloxan diabetic pancreas. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during thiazide therapy remains, however, uncertain.

Animals↗
PubMed1985

Hypoglycaemic coma in severe primary hypothyroidism.

A 76-year-old woman was admitted to the hospital in comatose condition. Her blood glucose was 1.7 mM. Immediately after intravenous glucose treatment she attained normal consciousness. The diagnosis of severe primary hypothyroidism was subsequently made and no sign of other diseases was detected. After thyroid replacement therapy fasting blood glucose levels rose to normal and no further hypoglycaemic episodes occurred. It is emphasized, that hypoglycaemia may be the direct cause of severely impaired consciousness in hypothyroidism requiring immediate and specific therapy.

Aged↗
PubMed1985

Forskolin, an activator of adenylate cyclase, stimulates pancreatic insulin, glucagon, and somatostatin release in the dog: studies in vitro.

Forskolin, a direct activator of adenylate cyclase, stimulates cAMP production in islet cells. The effects of forskolin on the release of somatostatin, glucagon, and insulin were studied using the isolated, perfused dog pancreas. It was found that concentrations ranging from 0.075 microM-1 microM stimulated the secretion of somatostatin, glucagon, and insulin in a dose-related manner. The effects of 0.15 microM and of 0.6 microM forskolin were modulated by the prevailing glucose level with higher D and B and lower A cell responses at high (11 mM) than at low (2.8 mM) or zero glucose. In the absence of extracellular Ca++, forskolin (1 microM) possessed no stimulatory effect on pancreatic hormone secretion. Perfusion of 1 microM atropine, 1 microM propranolol, and 1 microM phentolamine had no effect on forskolin-mediated (0.3 microM) hormone output from pancreas. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (25 microM) elicited qualitatively similar hormone response to forskolin. In conclusion, the experiments demonstrate that forskolin is a potent, reversible, stimulus of pancreatic hormone secretion. Its effects are apparently not mediated via the sympathetic or parasympathetic nerve endings in pancreas. Forskolin may prove to be a valuable pharmacological tool in probing the role of the adenylate cyclase-cAMP system in pancreatic hormone secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Somatostatin secretion from the isolated perfused dog ileum.

The present study was designed to examine ileal D cell function. The influence of perfusate calcium, potassium, arginine, and glucose on release of somatostatin (SS) was measured using an isolated, perfused dog ileum preparation. Ileal SS release was significantly enhanced by an increase in extracellular calcium from 0-1.3 mM (from 11 +/- 3 pg/ml to 37 +/- 11 pg/ml; 2 P less than 0.05). In the presence of a normal calcium level (1.3 mM) an increase in potassium from 4.4-13.8 mM caused enhanced SS output (from 46 +/- 8 pg/ml to 74 +/- 10 pg/ml; 2 P less than 0.05). The addition of arginine (10 mM) elicited a prominent rise in SS secretion (from 105 +/- 8 pg/ml to 184 +/- 30 pg/ml; 2 P less than 0.05) while enhancement in glucose from 5-20 mM was without effect (57 +/- 13 pg/ml vs. 57 +/- 14 pg/ml). Thus it appears that ileal D cells release SS in response to changes in certain appropriate stimuli, but in contrast to those D cells situated in other parts of the gastrointestinal tract, e.g. the pancreas, they are apparently nonresponsive to glucose.

Animals↗