Biomedical subjects

E Jennische

Publications and source records attributed to E Jennische.

At least 19 recordsLinked to original sources

PubMed2005

Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury.

Intestinal injury 4-48 hr after cytotoxic therapy (etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) and rubidium-86 chloride ((86)RbCl) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in (51)Cr-EDTA permeation and a decrease in (86)Rb absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.

Animals↗

PubMed2004

Increased antisecretory factor reduces vertigo in patients with Ménière's disease: a pilot study.

It has been hypothesized that the symptoms of vertigo in patients with Ménière's disease somehow are related to impaired production and/or transport of endolymph. Antisecretory factor (AF) is a protein known to affect transport processes in the intestine and it has been shown that intake of specially processed cereals (SPC) can increase endogenous AF synthesis. In a prospective open pilot study, 24 patients with severe Ménière's disease (functional level scale 5-6 according to the criteria of AAO-HNS) received SPC for 14-30 days. AF levels in plasma increased by 83% in 20 of the 24 patients studied. The attacks of rotatory vertigo were reduced, to final AAO-HNS functional level scale 1-3, in 12 patients and in three of these hearing was normalized. Twelve patients had no or minor effects of the treatment. The correlation between AF activity after treatment and the final AAO-HNS functional level scale was -0.65, P<0.001. Studies in rats using immunohistochemistry methods showed that AF was localized to the cochlea and the vestibule of the inner ear. The present results suggest that AF might be a new regulator of the endolymph.

Adult↗

PubMed2003

Antisecretory factor counteracts secretory diarrhoea of endocrine origin.

BACKGROUND: Dietary induction of antisecretory factor (AF) can reduce diarrhoea in patients with inflammatory bowel disease. Patients with neuroendocrine tumours may suffer from diarrhoea with a prominent secretory component. We studied if AF-therapy could affect this type of diarrhoea. METHODS: Six patients with the midgut carcinoid syndrome and two with metastasizing medullary thyroid carcinoma (MTC) participated. Effects of intake of AF, in the form of AF-rich egg powder (AF-egg), and induction of endogenous AF-activity by intake of specially processed cereals (SPCs) were studied. In an initial open part of the study all patients received AF-egg for 4 weeks, followed by a double-blind crossover period with SPC and control cereals (CCs) for 6 weeks each. Daily number of bowel movements at the end of each treatment period was registered. RESULTS: Treatment with AF-egg resulted in a decrease of bowel movements in seven patients (P<0.01). Registrations of bowel movements from both SPC and CC diet periods were obtained from five patients. The daily number of bowel movements was lower during the SPC-period compared to the period with CC (P<0.05). All patients had low levels of AF-activity in serum at baseline. During treatment with AF-egg, the mean level increased slightly. AF-activity was higher (P<0.05) after SPC compared to the CC diet. CONCLUSIONS: In a group of patients with endocrine diarrhoea, AF-activity could be induced, and AF-therapy reduced the number of bowel movements.

Antidiarrheals↗

PubMed2003

Effect of antisecretory factor in ulcerative colitis on histological and laborative outcome: a short period clinical trial.

BACKGROUND: The antisecretory factor (AF) is a 41 kD endogenously produced protein capable of mediating protection against diarrhoea diseases and intestinal inflammation. High concentrations of AF-like proteins are present in egg yolk, and AF can consequently be administrated in the form of egg yolk drinks. In this study, performed in patients suffering from acute onset of ulcerative colitis (UC), we evaluate the influence of orally administrated AF on the histological and clinical laboratory outcome. METHODS: A total of 20 patients fulfilled this prospective, double-blind and randomized protocol. The intake of AF was used as an additive treatment to conventional UC medication. Patient registrations were extended to two outward visits, performed 2-4 and 8-12 weeks after hospital discharge. RESULTS: During AF treatment, a reduction in the histological severity from mucosal biopsies received from the mid-rectum was found. In addition, a lowering in the inflammatory blood parameters ESR, CRP and orosomucoid was demonstrated. CONCLUSION: In the AF-treated group a late and significant lowering of various inflammatory parameters combined with a histological recovery was demonstrated. These findings suggest that administration of AF mediates a long-lasting anti-inflammatory effect in cases of acute UC.

Administration, Oral↗

PubMed2001

Prenatal cytokine exposure results in obesity and gender-specific programming.

Prenatal events appear to program hormonal homeostasis, contributing to the development of somatic disorders at an adult age. The aim of this study was to examine whether maternal exposure to cytokines or to dexamethasone (Dxm) would be followed by hormonal consequences in the offspring at adult age. Pregnant rats were injected on days 8, 10, and 12 of gestation with either human interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-alpha) or with Dxm. Control dams were injected with vehicle. All exposed offspring developed increased body weight (P < 0.05--0.001), apparently due to an increase of 30--40% in adipose tissue weight (P < 0.05--0.01). Corticosterone response to stress was increased in the IL-6 group (P < 0.05-0.01). Dxm-treated male rats exhibited blunted Dexamethasone suppression test results. In male rats, insulin sensitivity was decreased after IL-6 exposure (P < 0.01), whereas basal insulin was elevated in the TNF-alpha group (P < 0.01). In female rats, plasma testosterone levels were higher in all exposed groups compared with controls (P < 0.01--0.001), with the exception of Dxm-exposed offspring. Males in the TNF-alpha group showed decreased locomotor activity (P < 0.05), and females in the IL-6 group showed increased locomotor activity (P < 0.05). These results indicate that prenatal exposure to cytokines or Dxm leads to increased fat depots in both genders. In females, cytokine exposure was followed by a state of hyperandrogenicity. The results suggest that prenatal exposure to cytokines or Dxm can induce gender-specific programming of neuroendocrine regulation with consequences in adult life.

Adipose Tissue↗

PubMed2001

Maternal endotoxemia results in obesity and insulin resistance in adult male offspring.

Events in utero appear to be important factors contributing to the development of somatic disorders at adult age. The aim of this study was to examine whether maternal immune challenge would be followed at adult age by metabolic and endocrine abnormalities in the offspring. Pregnant rats were given injections of either endotoxin (Escherichia coli lipopolysaccharide; 0.79 mg/kg, ip) or vehicle on days 8, 10, and 12 of gestation. Adult male offspring to lipopolysaccharide-exposed dams were heavier than controls (P < 0.05) and showed increased adipose tissue weights (P < 0.05), elevated food intake (P < 0.05), and increased circulating leptin (P < 0.01). The effect of insulin on glucose uptake was reduced, as measured by an euglycemic hyperinsulinemic clamp technique (P < 0.05). Serum levels of 17beta-estradiol and progesterone were elevated (P < 0.01 and P < 0.05, respectively). Baseline levels of corticosterone were normal, but the corticosterone response to stress was attenuated (P < 0.05), and hippocampal glucocorticoid receptor protein was up-regulated (P < 0.05). Female offspring were uninfluenced, except for increased testosterone levels (P < 0.05), increased baseline corticosterone levels (P < 0.05), and enlargement of heart and adrenals (P < 0.05). The results indicate that maternal endotoxemia leads to obesity, insulin resistance, and high serum levels of leptin in the adult male offspring. This study reports a novel animal model of obesity with features of the metabolic syndrome.

Adipose Tissue↗

PubMed2000

Expression and localisation of IGF-binding protein mRNAs in regenerating rat skeletal muscle.

The expression of the insulin-like growth factor-binding proteins (IGFBP) -3, -4, -5 and -6 was investigated in neonatal, in normal adult and in regenerating rat skeletal muscle. Semi-quantification was done by densitometric scannings of Northern blots. The expression of all investigated IGFBPs, with the exception of IGFBP-5, was higher in neonatal than in adult muscle. During postischaemic regeneration the expression of all IGFBPs increased, but with different time schedules. IGFBP-3 increased transiently during the early phase of regeneration, while IGFBP-4, -5 and -6 increased during the later phase of regeneration. In situ hybridisation on regenerating muscle showed that the expression of the various IGFBPs was cell specific; thus, IGFBP 3 was mainly expressed in macrophages, IGFBP-4 in connective tissue, IGFBP-5 in regenerating muscle cells, and IGFBP-6 in muscle cells, connective tissue and endothelium. Ligand blotting, using 125I-IGF-I as the ligand, showed a number of bands ranging between 24 and 44 kDa. Samples from neonatal and regenerating muscle contained much higher levels of all IGFBPs than those from normal adult muscle. An ordered and cell-specific expression of IGFBPs, allowing a strict regulation of IGF actions, is probably necessary to ensure an optimal regeneration process.

Animals↗

PubMed2000

Food induced stimulation of the antisecretory factor can improve symptoms in human inflammatory bowel disease: a study of a concept.

BACKGROUND: Antisecretory factor (AF), a 41 kDa cloned and sequenced protein, suppresses intestinal inflammation and hypersecretion in animals. Endogenous AF production can be induced by dietary modifications in several animal species, and this feed has been shown to reduce the incidence of diarrhoeal disease in weaning piglets. The role of AF in intestinal disease in humans is not known. AIMS: To study the effects of hydrothermally processed cereals, optimised for AF induction in animals, added to the diet of patients with longstanding symptoms of inflammatory bowel disease (IBD). PATIENTS: Fifty three patients with IBD (ulcerative colitis and Crohn's disease) were entered into the study, and 50 completed follow up. The experimental group consisted of 16 females (mean age 50 (SEM 5) years) and 10 males (41 (4) years) and the placebo group of 12 women (41 (4) years old) and 12 men (51 (5) years). METHODS: Patients were randomised to receive either hydrothermally processed cereals (active treatment) or the same amount of ordinary cereals (placebo treatment) for four weeks in a double blind study design. Baseline diet and medications remained unchanged. Bowel symptoms, plasma levels of AF, and colonic biopsies were evaluated before and after treatment. RESULTS: The active treatment significantly improved subjective ratings of clinical symptoms and increased plasma AF levels compared with placebo. Plasma lipid levels were unaffected. CONCLUSION: Hydrothermally processed cereals can induce AF production in human IBD. This increase in endogenous AF activity is associated with clinical improvement. Further studies are warranted to clarify the exact role of AF in human intestinal disease.

Adult↗

PubMed1999

The antisecretory factor: synthesis and intracellular localisation in porcine tissues.

The antisecretory factor, AF, is a 41-kDa protein, cloned and sequenced from a human pituitary library. AF is a potent inhibitor of experimental intestinal hypersecretion in rats and pigs. An antiserum against the C-terminal of the truncated, recombinantly produced AF protein was raised in rabbits. The affinity-purified antiserum was used to study the expression of AF in mucosal membranes and in the pituitary gland of the pig; distinctly stained cells were found in lymphoid cells in the connective tissue of all parts of the gastrointestinal, respiratory and urinary tracts. Cytoplasmic AF was demonstrated in endocrine and epithelial cells in the pituitary gland. In situ hybridisation with a digoxigenin-labelled mRNA probe also demonstrated specific cytoplasmic staining in epithelial and lymphoid cells in all of these tissues. The cells stained by either method were similarly distributed topographically within the tissues. The results suggest that a specific defined cell population in these various tissues possesses the capability of both synthesising and storing the AF protein within the cellular cytoplasmic compartment.

Animals↗

PubMed1998

Recombinant or plasma-derived antisecretory factor inhibits cholera toxin-induced increase in Evans blue permeation of rat intestinal capillaries.

The effect of cholera toxin on small intestinal capillary function, utilizing the Evans blue dye method, was analyzed. The modulatory influence of plasma-derived or recombinant human antisecretory factor on this variable was also investigated. Male Sprague-Dawley rats were briefly anesthetized with ether, and a jejunal loop was constructed that was challenged for 90 min with phosphate-buffered saline or cholera toxin. Five minutes prior to death, the rats received an intravenous injection of Evans blue. The tissue content of dye in the loop was quantitated spectrophotometrically or demonstrated histochemically. Cholera toxin increased the recovery of Evans blue; extravasation of the dye was prominent in the top of the villi, while the crypts were spared. It is suggested that the toxin caused increased transcapillary permeation of albumin in a heterogenous fashion in the gut wall. This effect of the toxin was prevented by pretreatment with the antisecretory factor.

Animals↗

PubMed1997

Influence of topical rectal application of drugs on dextran sulfate-induced colitis in rats.

A rat model of colitis [dextran sulfate (DSS)] was used to study the permeation of Evans blue (EB) from the lumen into the wall of proximal and distal colonic loops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerative colitis (lidocaine, mesalazine, prednisolone, or sucralfate) was given daily during induction of colitis to protect the mucosa. The mucosal changes were evaluated with special regard to peptidergic innervation [substance P (SP) and neuropeptide Y (NPY)], invasion of antigen-presenting polydendritic cells, and mucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. In the proximal loops a significant inhibition was obtained after treatment with lidocaine, prednisolone, or sucralfate. In the distal loops only treatment with lidocaine had a preventive effect. Immunocytochemically there was a clear hyperplasia of both mucosal SP- and NPY-immunoreactive nerve fibers in regions with crypt abnormalities. In these regions also most of the goblet cells were devoid of mucus. Like the changes in permeation, these morphological changes were most prominent in the distal loops. With induction of colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visual score was markedly decreased in the proximal loops treated with lidocaine, prednisolone, or sucralfate. In the distal loops similar effects were obtained after treatment with lidocaine or prednisolone. Prevention of the influx of antigens in both loops after lidocaine treatment with reduced recruitment of polydendritic cells into the lamina propria is suggested. The nerve hyperplasia may thus be secondary to luminal challenge with antigens during induction of colitis. The discrepancy between increased permeation and absence of polydendritic cell response in the distal loops after prednisolone may reflect separate actions of steroids on the intestinal epithelium and the immune cells.

Administration, Rectal↗

PubMed1997

Growth hormone improves cardiac function in rats with experimental myocardial infarction.

Accumulating evidence suggests from experimental and clinical studies beneficial effects of growth hormone (GH) on contractility, although concomitant cardiac hypertrophy, generally considered to be a cardiovascular risk factor, has also been reported. In the present study, we combine a rat model with impaired cardiac performance after myocardial infarction (MI) with echocardiographic evaluation of GH effects on cardiac structure and function. We have used a rat model with ligation of the left coronary artery in normal, growing male rats resulting in subsequent impaired cardiac performance. After 6 weeks' recovery, blind transthoracic echocardiography was performed to determine infarction size, cardiac geometry and performance. Rats with no signs of myocardial infarction were excluded from the study. After randomization, the rats were treated with daily s.c. injections of saline (n = 8) or recombinant human growth hormone (rhGH) (n = 6) at a dose of approximately 1 mg kg-1 body weight for 1 week. A new blind echocardiography examination was performed after treatment demonstrating a 13% increase in ejection fraction (EF) and a 50% increase in cardiac index in GH-treated rats compared with control rats (P < 0.01). Moreover, GH caused a significant decrease in end-systolic volume. There were no significant changes in left ventricular (LV) or interventricular wall thickness, LV dimensions, heart rate or diastolic function. No effects were seen on LV weight, cardiac insulin-like growth factor (IGF) I, IGF-I receptor and GH receptor mRNA content. GH in a physiological dose improves systolic function in an experimental model of heart failure without signs of hypertrophy, suggesting a potential role as a therapeutic agent in the treatment of heart failure and merits further investigation.

Animals↗

PubMed1997

Antisecretory factor suppresses intestinal inflammation and hypersecretion.

BACKGROUND: Antisecretory factor (AF) is a recently identified regulatory protein which inhibits the intestinal fluid secretion induced by cholera toxin. AIMS: To test the effect of AF on: (a) inflammation and hypersecretion induced by toxin A from Clostridium difficile; and (b) morphological changes and hypersecretion induced by okadaic acid (the blue mussel toxin) in rat intestinal mucosa. METHODS: Morphological changes and fluid accumulation were observed in intestinal loops challenged with 1 microgram of toxin A or 3 micrograms of okadaic acid administered before or after injection of 0.1 microgram of recombinant AF (rAF). RESULTS: The cytotoxic and inflammatory reaction caused by toxin A was abolished after treatment with rAF given either intraveneously or intraluminally prior to the toxin or one hour after the toxin. The intestinal fluid response induced by toxin A and okadaic acid was reduced 55-80% by rAF. However, the characteristic increase in goblet cells at the tips of villi in the okadaic acid treated mucosa was not inhibited by rAF. CONCLUSION: Results suggest that AF might be involved in protection against inflammation and in counteracting dehydration caused by enterotoxins. Both effects are probably mediated via the enteric nervous system.

Animals↗

PubMed1996

Rapid formation of capillary endothelial cells in rat skeletal muscle after exposure to insulin.

Research has suggested a role for insulin delivery through capillaries in muscle in the regulation of insulin sensitivity. Therefore, the formation and turn-over of capillary endothelial cells in muscle were studied in relation to exposure to moderately elevated insulin concentrations with or without concomitant increase of corticosterone concentrations. Female rats were exposed to a moderate, physiological hyperinsulinaemia (approximately 450 pmol/l) for 24 h 48 h, 3 days, 7 days and 7 weeks. Propranolol was used to inhibit elevated adrenergic activity. In one insulin-exposed group, corticosterone secretion was controlled by adrenalectomy with substitution of corticosterone to maintain normal concentrations, while another group was left with adrenal corticosterone secretion intact. Rats were exposed to insulin with controlled, non-elevated corticosterone concentrations after adrenalectomy and corticosterone substitution; compared to controls, the number of mitoses in capillary endothelial cells in the soleus and extensor digitorum longus muscle were approximately doubled after 24 h, reaching a maximum, about fivefold higher than controls, after 3 days. After 7 weeks of insulin exposure there were no longer any significant differences between control and insulin-exposed rats. The number of capillaries per unit muscle surface area was moderately (10-15%) but significantly increased at 7 days (only the extensor digitorum longus muscle) and 7 weeks (the extensor digitorum longus and the soleus muscles). In rats exposed to insulin, with intact adrenals, endogenous corticosterone production resulted in concentrations about threefold higher than in rats adrenalectomized with subsequent corticosterone substitution. In these rats the increase in mitoses in capillary endothelium was totally abolished. The results of this study suggest that exposure to insulin in this rat model is followed by a dramatic short-term increase in the formation of new capillary endothelial cells in muscle. It is also suggested that this growth factor-like effect of insulin is abolished by corticosterone. It is suggested that insulin and corticosterone exert opposite effects on the capillary network in muscles, which might be important for the insulin supply to this tissue, and hence for regulation of insulin sensitivity.

Adrenalectomy↗

PubMed1996

The effects of hyperinsulinaemia on myocardial mass, blood pressure regulation and central haemodynamics in rats.

Left ventricular hypertrophy is a condition with high mortality. An association with insulin resistance and hyperinsulinaemia has recently been suggested. The aim of this study was to examine the effects of isolated hyperinsulinaemia on cardiac weight and haemodynamic regulation. Rats were exposed to hyperinsulinaemia for 7 weeks after adrenalectomy with corticosterone substitution and continuous infusion of propranolol to control counter-regulatory mechanism (n = 15) (AIP group). Hypoglycaemia was prevented by glucose in the drinking water. Hyperinsulinaemic (AIP) rats were heavier and had increased relative masses of the myocardium (left ventricle 17% and right ventricle 20%), kidneys and adipose tissues in comparison with normoinsulinaemic adrenalectomized, corticosterone- and propranolol-treated controls (AP) (n = 10). Blood pressure in the insulin-exposed animals, measured weekly by the tail-cuff method in conscious rats, was not different from (AP) controls over 5 weeks, but increased in the sixth week. At the end of the seventh experimental week, blood pressure measured intra-arterially was also found to be elevated. Heart rate was not changed but total peripheral resistance was about twice that of controls (P < 0.001). Cardiac output and stroke volume was 30-40% lower in the AIP rats (P < 0.05). It is concluded that exposure to elevated insulin levels with control of counter-regulating mechanisms from beta-adrenergic mechanisms and adrenals is not immediately followed by blood pressure elevation. It is, therefore, suggested that early onset of blood pressure elevation after insulin exposure might be caused by insulin counter-regulatory events, causing both insulin resistance and blood pressure elevation. The long-term adaptations may involve a direct influence by insulin as a 'trophic factor' on myocardial and on peripheral resistance levels, followed by increased blood pressure, decreased cardiac and stroke volume.

Animals↗

PubMed1996

The role of the Lps gene in experimental ulcerative colitis in mice.

The effects of the Lps gene on the development of experimental ulcerative colitis were studied in two genetically different mouse strains: C57B1 and C3H. Acute colitis was induced by adding 3% dextran sulfate sodium (DSS) to the drinking water for a 7-day (C57B1 and C3H) or a 10-day (C57B1) experimental period. Although the DSS treatment initiated the same type of morphological changes in the colon in all groups of mice, an earlier onset and persistent intestinal bleeding occurred in the Lpsn mice (sensitive to lipopolysaccharide, LPS) in comparison with the Lpsd mice (hyporesponsive to LPS). Rectal bleeding appeared on day 7 in 90% of the Lpsn compared to 13% of the Lpsd mice (p < 0.0001). In C57B1 mice, followed for three additional days, 50% of the Lpsn mice died and the surviving animals showed as well as rectal bleeding a large number of Gram-negative bacteria in the liver and spleen. In contrast, the Lpsd mice of the C57B1 strain appeared unaffected by the treatment, although a transient rectal bleeding occurred in 90% on day 8. Also, significantly fewer Gram-negative bacteria were found in the liver and spleen. Even though significantly increased serum endotoxin levels were seen in all DSS-treated groups compared to controls on day 7, the serum levels of TNF alpha were significantly increased only in the Lpsn mice. In DSS-induced colitis the Lpsn genotype conferred on the mice an increased LPS susceptibility, resulting in an augmentation of the inflammatory response to Gram-negative bacteria and their endotoxins. The results suggest that LPS-induced host effector mechanisms significantly enhanced the intestinal bleeding, systemic inflammatory response, and mortality in mice with DSS-induced colitis. In addition, the host defense against the invading and systemically spread bacteria most probably involved additional genes.

Animals↗

PubMed1995

Molecular cloning and expression of a pituitary gland protein modulating intestinal fluid secretion.

Antisecretory factor (AF) is a protein known to inhibit intestinal fluid secretion induced by cholera toxin. cDNA clones, expressing immunoreactivity to AF were isolated from a human pituitary gland library and sequenced. The sequence contained 1309 base pairs plus a poly(A) tail; Northern blot analysis of pituitary RNA confirmed this size. One large open reading frame was found to code for 382 amino acids. The protein was expressed in pGEX-lambda 1T/Escherichia coli and purified. The recombinant AF was extremely potent, 9 ng (2.10(-13) mol), giving a significant antisecretory activity against cholera toxin-induced fluid secretion in rat. Antiserum against recombinant AF was used in immunohistochemical and Western blot analysis. Sections from human pituitary glands manifested specific intracellular staining in cells exclusively located in the anterior part. Both recombinant AF and AF extracted from pituitary gland appeared in SDS-polyacrylamide to have a molecular mass of 60 kDa, although the renal value was 41 kDa. The protein sequence manifested homology (29% identity) with one protein, a putative Saccharomyces cerevisiae 30-kDa protein of unknown function.

Amino Acid Sequence↗

PubMed1995

The effects of long-term hyperinsulinaemia on insulin sensitivity in rats.

The effects of long-term exposure (7 wk) to hyperinsulinaemia on insulin sensitivity were studied in female rats. The rats were made hyperinsulinaemic by implantation of osmotic minipumps that were changed once a week. Elevated adrenergic activity and secretion of glucocorticoids were controlled by another minipump with propranolol and adrenalectomy with corticosterone substitution, respectively. This resulted in hyperinsulinaemia and moderate hypoglycaemia, the latter probably counteracted by overeating and increased glucagon secretion, as indicated by increased body weight and lower liver glycogen contents, respectively. Euglycaemic, hyperinsulinaemic clamp measurements showed a significantly higher glucose disposal rate (P < 0.05) in the hyperinsulinaemic rats 18.8 +/- 1.1 mg kg-1 min-1 compared with the control groups 14.6 +/- 0.4 and 15.4 +/- 0.9 mg kg-1 min-1. Insulin stimulation of 2-deoxyglucose as well as glycogen synthesis was measured in the extensor digitorum longus muscle, the red and white part of the gastrocnemius, the soleus muscle, the liver and in parametrial, retroperitoneal, and inguinal adipose tissue. No differences were found between the groups in the insulin response of the 2-deoxyglucose uptake. Glycogen synthesis was significantly elevated in all muscles in the insulin treated compared with the control rats but no differences were found in the liver. Capillary density was significantly elevated per unit muscle surface area in the soleus and extensor digitorum longus muscles of the insulin-exposed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗