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Biomedical subjects

L H Storlien

Publications and source records attributed to L H Storlien.

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

Fish oil prevents insulin resistance induced by high-fat feeding in rats.

Non-insulin-dependent diabetes mellitus is an increasingly prevalent disease in Western and developing societies. A major metabolic abnormality of non-insulin-dependent diabetes is impaired insulin action (insulin resistance). Diets high in fat from vegetable and nonaquatic animal sources (rich in linoleic acid, an omega-6 fatty acid, and saturated fats) lead to insulin resistance. In rats fed high-fat diets, replacement of only 6 percent of the linoleic omega-6 fatty acids from safflower oil with long-chain polyunsaturated omega-3 fatty acids from fish oil prevented the development of insulin resistance. The effect was most pronounced in the liver and skeletal muscle, which have important roles in glucose supply and demand. The results may be important for therapy or prevention of non-insulin-dependent diabetes mellitus.

Adipose Tissue↗
PubMed1987

Cephalic phase metabolic responses in normal weight adults.

The presence and physiologic importance of cephalic phase insulin release in humans remains controversial. The aim of these studies was to determine whether cephalic phase insulin release could be demonstrated in normal weight subjects and whether it would be associated with changes in blood glucose, free fatty acid, and pancreatic polypeptide levels. The studies were followed by a hyperglycemic clamp to determine whether cephalic responses would alter overall glucose disposal or glucose-stimulated insulin secretion. In all, 17 subjects were studied on two occasions with and without (control study) presentation of food stimuli. Tease-feeding alone (n = 6), or the administration of a sweet taste alone (aspartame, n = 5) failed to stimulate cephalic responses. However, the presentation of the combined stimuli (tease meals plus sweet taste, n = 7) resulted in a significant fall (P less than .005) in blood glucose levels and a variable rise in serum insulin (% insulin rise 38 +/- 15%, P less than .05) and C-peptide levels (7 +/- 6%, NS) within five minutes of the food presentation when compared with control studies, with no change seen in free fatty acid or pancreatic polypeptide levels. The blood glucose fall correlated strongly (r = .90, P less than .01) with a score of the subjective response to the food and taste.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Assessment of obesity in early childhood.

Measures of physical development were gathered at birth and at ages 3, 5 and 7 years on a sample of over 800 children as part of a multidisciplinary development study. Direct measures of obesity (skinfolds, visual estimate and calculated fat body mass) were correlated with a range of indices based on height and weight (Eid, Ponderal, Quetelet's or Body Mass Index [BMI] and a modified BMI) to determine a valid and reliable index of obesity. Quetelet's or BMI (weight divided by height squared) was found to be the best index of obesity, correlating between 0.88 and 0.96 with percentage fat body mass at ages 5 and 7 years. The BMI also correlated consistently higher indices with all direct measures of body fat than did the other indices. The results indicate that in children, as in adults, BMI can be used to assess obesity simply. It has several advantages, being easy to collect, non-invasive, objective, and requires no special equipment or highly trained personnel. Finally, the BMI, involving as it does only height and weight, can be used to assess obesity retrospectively in the numerous populations which have records of height and weight.

Anthropometry↗
PubMed1986

In vivo insulin resistance in individual peripheral tissues of the high fat fed rat: assessment by euglycaemic clamp plus deoxyglucose administration.

We have examined peripheral insulin action in conscious rats chronically fed high fat (60% calories as fat) or high carbohydrate (lab chow) diets using the euglycaemic clamp plus 3H-2-deoxyglucose technique. A response parameter of individual tissue glucose metabolic rate (the glucose metabolic index, based on tissue deoxyglucose phosphorylation) was used to assess diet effects in eight skeletal muscle types, heart, lung and white and brown adipose tissue. Comparing high fat with high carbohydrate fed rats, basal glucose metabolism was only mildly reduced in skeletal muscle (only diaphragm was significant, p less than 0.05), but was more substantially reduced in other tissues (e.g. white adipose tissue 61% and heart 33%). No evidence of basal hyperinsulinaemia was found. In contrast, widespread insulin resistance was found during the hyperinsulinaemic clamp (150 mU/l) in high fat fed animals; mean whole body net glucose utilization was 34% lower (p less than 0.01), and the glucose metabolic index was lower in skeletal muscle (14 to 56%, p less than 0.05 in 6 out of 8 muscles), white adipose (27%, p less than 0.05) and brown adipose tissue (76%, p less than 0.01). The glucose metabolic index was also lower at maximal insulin levels in muscle and fat, suggesting the major effect of a high fat diet was a loss of insulin responsiveness. White adipose tissue differed from muscle in that incremental responses (maximal insulin minus basal) were not reduced by high fat feeding. The heart showed an effect opposite to other tissues, with an increase in insulin-stimulated glucose metabolism in high fat versus chow fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1986

Ovarian hormone effects on activity, glucoregulation and thyroid hormones in the rat.

Ovarian hormonal influences on the range of physiological and behavioral variables which combine to affect overall energy balance are poorly delineated. In the present study 4 groups of virgin, female rats (intact, ovariectomized, ovariectomized with estrogen replacement and ovariectomized with estrogen plus progesterone) were allowed access to running wheels and activity; food intake and weight gain were measured initially under food restricted, then under ad lib conditions. Serum insulin, glucose, thyroxine (T4) and triiodothyronine (T3) were determined on trunk blood samples obtained at the end of the experiment. Ovariectomy resulted in an increased rate of weight gain through reduced activity and T3 but food intake was unchanged. Insulin levels were greatly reduced. Estrogen replacement restored activity to the intact group's level and normalized weight gain. Insulin and T3 were also raised to control levels but T4 was reduced as was serum glucose. Estrogen plus progesterone replacement reduced weight gain markedly and increased T3 with normal T4. Despite the lower body weight this group was hyperglycemic and hyperinsulinemic suggesting insulin resistance. The results have important implications for the glucoregulatory and energy balance perturbations of ovarian hormone fluctuations and focus particularly on progesterone.

Animals↗
PubMed1986

Effects of scheduled food and water deprivation on food intake, water intake and body weight of cage-adapted and cage-naive rats.

The first experiment examined the effects of four food-deprivation schedules and four water-deprivation schedules on body weight, food intake and water intake of adult rats over ten days of deprivation and two days of recovery. During food deprivation, water intake was gradually reduced. During water deprivation, daily food intake was initially depressed but eventually returned to ad libitum levels. Consumption of restricted commodities increased over the deprivation phase. Experiment 2 showed that mutual deprivation of food and water are more apparent in rats not previously adapted to the test environment and the final experiment indicated that this was due to the inexperience of cage-naive rats in feeding under novel conditions. The results are evaluated in relation to the environmental factors that may play as great a role as physiological processes in regulating the feeding/drinking behaviour of laboratory rats.

Animals↗
PubMed1986

Heterogeneity of insulin action in muscle: influence of blood flow.

The influence of blood flow (BF) and basal neuromotor tone on in vivo insulin-stimulated glucose uptake (Rg') in muscle was examined using the euglycemic clamp plus deoxyglucose/glucose tracer (insulin action) and labeled microsphere (BF) techniques. Anesthesia was used to produce perturbations in BF and/or activity compared with conscious rats. An index of muscle glycolytic flux (Gf) was estimated from Rg' in excess of glycogen synthesis. Gf and glycogen synthesis were significantly increased in soleus and red gastrocnemius (RG) during insulin infusion (150 mU/l) in conscious rats. Rg' was related to muscle BF in conscious rats (r = 0.92). In anesthetized rats, Rg' and BF were reduced in soleus, RG, red quadriceps, and plantaris (e.g., soleus 69%, P less than 0.001, and 80%, P less than 0.001, respectively). However, it is unlikely that Rg' and BF are causally related because fractional extraction of glucose by muscle was low (approximately 9%); fractional extraction increased during anesthesia (17%, P less than 0.01); BF but not Rg' was reduced by anesthesia in extensor digitorum longus, white gastrocnemius, and white quadriceps; and reduced Rg' during anesthesia in soleus and RG was mainly due to reduced GF. In conclusion, BF is not a major contributor to the heterogeneity in insulin-stimulated glucose uptake among individual muscles under basal conditions. These data suggest that neuromotor tone may indirectly influence the magnitude of muscle glucose uptake during insulin elevation via a substrate switching effect. This may give rise to a significant increase in glycolytic flux of glucose in those muscles that exhibit elevated activity even at rest (e.g., soleus).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1986

Fat feeding causes widespread in vivo insulin resistance, decreased energy expenditure, and obesity in rats.

High levels of dietary fat may contribute to both insulin resistance and obesity in humans but evidence is limited. The euglycemic clamp technique combined with tracer administration was used to study insulin action in vivo in liver and individual peripheral tissues after fat feeding. Basal and nutrient-stimulated metabolic rate was assessed by open-circuit respirometry. Adult male rats were pair-fed isocaloric diets high in either carbohydrate (69% of calories; HiCHO) or fat (59% of calories; HiFAT) for 24 +/- 1 days. Feeding of the HiFAT diet resulted in a greater than 50% reduction in net whole-body glucose utilization at midphysiological insulin levels (90-100 mU/l) due to both reduced glucose disposal and, to a lesser extent, failure to suppress liver glucose output. Major suppressive effects of the HiFAT diet on glucose uptake were found in oxidative skeletal muscles (29-61%) and in brown adipose tissue (BAT; 78-90%), the latter accounting for over 20% of the whole-body effect. There was no difference in basal metabolic rate but thermogenesis in response to glucose ingestion was higher in the HiCHO group. In contrast to their reduced BAT weight, the HiFAT group accumulated more white adipose tissue, consistent with reduced energy expenditure. HiFAT feeding also resulted in major decreases in basal and insulin-stimulated conversion of glucose to lipid in liver (26-60%) and brown adipose tissue (88-90%) with relatively less effect in white adipose (0-43%). We conclude that high-fat feeding results in insulin resistance due mainly to effects in oxidative skeletal muscle and BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Guanethidine blocks the 2-deoxy-D-glucose-induced hypothalamic noradrenergic drive to hyperglycemia.

To determine whether 2-deoxy-D-glucose (2-DG)-induced hyperglycemia is neurally mediated we administered guanethidine, an adrenergic neuron blocker, to 2-DG-treated rats. While 2-DG increased both medial basal hypothalamic noradrenergic neuronal activity (MBH NNA) and serum glucose, the rise in serum glucose was blocked by guanethidine while MBH NNA was even further increased. We conclude that 2-DG-induced hypothalamic noradrenergic drive to hyperglycemia is mediated by direct sympathetic nervous system activation of liver glucose output.

Animals↗
PubMed1985

The role of the ventromedial hypothalamic area in periprandial glucoregulation.

There is a great deal of evidence that the ventromedial hypothalamic area (VMH) plays a significant role in glucoregulation. The present review synthesizes new and existing data in a coherent model of a hypothalamic glucoregulatory control system whose function is to stabilize blood glucose levels in the face of discontinuous exogenous supply attendant upon meal-feeding. Evidence is arrayed which suggest the VMH is critical in initiating the anticipatory insulin secretion in advance of the meal-related rise in blood-borne nutrients; that insulin rise acts as a messenger to the brain to reduce both CNS glucose utilization and endogenous glucose production in anticipation of the prandial glucose rise; that the VMH suppresses the reactive phase of insulin secretion which occurs in response to rising blood borne nutrients and finally that the VMH acts to restore endogenous production postprandially to ensure a smooth transition from use of exogenous, meal-derived energy back to endogenous stores. The net effect of this VMH modulation would be minimal periprandial glycemic perturbation. Implications of the model for diabetes and weight regulation are discussed.

Animals↗
PubMed1985

Development of hypoglycemia and hyperglycemia as a function of number of trials in insulin conditioning.

A neutral environment paired with insulin injections can develop the capacity to elicit glycemic changes. However, both conditioned hypoglycemia and conditioned hyperglycemia have been reported under apparently similar circumstances. The present study examined conditioned glycemic changes as a function of the number of conditioning trials and the novelty of the conditioning environment. Adult, male Wistar rats were injected with either insulin or physiological saline every second day, in either a novel or a familiar environment. On the test day, all rats were injected with saline and blood was collected 20 minutes later for determination of glucose levels. In rats given insulin in the novel environment, conditioned hypoglycemia was observed after two trials but was replaced by conditioned hyperglycemia after five trials. No conditioning at all occurred in the familiar environment. The two conditioned responses observed were interpreted as reflecting two unconditioned responses brought about by insulin--a hypoglycemic response to the central detection of insulin, and a hyperglycemic response to the detection of (insulin-induced) hypoglycemia. Taken in conjunction with previous experiments in which both conditioned response patterns have occurred, the present results suggest that the homeostatic response of hyperglycemia can become strong enough to overcome the initial conditioned response of hypoglycemia, but that its establishment depends on the use of a novel conditioned stimulus and a larger number of conditioning trials.

Animals↗
PubMed1985

Effects of chronic lithium, amitriptyline and mianserin on glucoregulation, corticosterone and energy balance in the rat.

Major negative side-effects reported for mood-stabilizing and antidepressant drugs in humans are excess weight gain and carbohydrate craving. The aim of the present study was to establish whether the rat could usefully be employed in investigation of these phenomena. Three experiments investigated the effects of chronic lithium (40 mg/kg LiCl), amitriptyline (2.5 mg/kg), mianserin (2.5 mg/kg) and saline administration (15-20 days, one subcutaneous injection/day) on body weight, food intake and fluid intake. Water and food cubes were provided in all experiments. Additionally available, as separate fluid sources, in Experiment 2 were 24% sucrose and 0.6% saccharin and in Experiment 3, 0.6% saccharin. Blood was collected for plasma glucose and insulin determinations 20-24 hours after the final injections. Lithium administration resulted in a marked increase in weight gain but only if both sucrose and saccharin were available (Experiment 2). Saccharin intake was increased with lithium treatment as was total caloric intake with sucrose available. Amitriptyline induced a sweetness craving; however, weight gain was somewhat depressed with just cubes available (Experiment 1) and only normalised by the additional availability of sucrose and saccharin (Experiment 2). With amitriptyline, total caloric intake was never different from controls. Weight gain was slightly suppressed and caloric intake slightly elevated by mianserin but importantly the two effects combined for a decrease in metabolic efficiency which was particularly exaggerated under the condition of carbohydrate availability (Experiment 2). Lithium and amitriptyline both produced hyperinsulinemia with normoglycemia whether or not the rate of weight gain was changed and whether or not intake was increased. Corticosterone levels were elevated by all drug treatments in Experiment 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitriptyline↗
PubMed1985

The ventromedial hypothalamic area and the vagus are neural substrates for anticipatory insulin release.

It has been clearly demonstrated in a number of animal species including man, that insulin secretion can occur in response to sensory stimuli associated with meal taking and in advance of any ingestional rise in blood nutrients. The neural basis of this anticipatory insulin rise is poorly delineated and was therefore investigated in two experiments. In the first, rats with electrolytic lesions of the ventromedial hypothalamic area (VMH), or sham lesions were assessed and in the second experiment rats with bilateral subdiaphragmatic vagotomies or sham vagotomies were studied. In both experiments rats with jugular cannulae were conditioned to expect a meal 5 min following the beginning of a complex (light, tone and odor) stimulus. On the test trial the stimulus was given but no meal was forthcoming. Blood was sampled via the jugular catheter before and during the stimulus presentation. In both experiments the control rats showed a significant insulin rise during the stimulus presentation. However, neither the VMH-lesioned nor the vagotomized rats showed any significant change in insulin levels. The results clearly demonstrate an insulin rise to a complex sensory stimulus which has been paired with food and further show the dependence of that response on the integrity of the hypothalamic-vagal-visceral neural pathway. It is suggested that the VMH receives meal-associated sensory input and employs that information to prepare the animal metabolically for incoming nutrients. One aspect of this anticipatory mechanism is a vagally mediated insulin secretion.

Animals↗
PubMed1985

Hyperinsulinemia suppresses glucose utilization in specific brain regions: in vivo studies using the euglycemic clamp in the rat.

It has been suggested that insulin acts centrally by altering brain glucose uptake. Previous studies of the effect of insulin on brain glucose metabolism have been difficult to interpret due to lack of steady state conditions for glucose and/or insulin. To determine whether insulin per se alters brain glucose metabolism, we measured glucose utilization rates, using the deoxyglucose method, in the medial basal hypothalamus, locus coeruleus, and motor cortex of conscious, unrestrained rats undergoing 2-h euglycemic clamps (blood glucose, 4.1 +/- 0.1 mmol/liter) at increasing insulin infusion rates. Plateau insulin levels were 29 +/- 5 mU/liter (controls) and 48 +/- 4, 146 +/- 8, 670 +/- 40, and 7560 +/- 410 mU/liter (clamped). Glucose utilization rates in the medial basal hypothalamus fell significantly from 60 +/- 4 mumol/100 g X min (controls) to 46 +/- 3, 39 +/- 2, 35 +/- 2, and 39 +/- 3 mumol/100 g X min in respective insulin-infused animals (P less than 0.01 vs. controls). Similar falls of up to 39% and 48% were seen in the locus coeruleus and motor cortex, respectively. A significant inverse correlation was found between the glucose utilization rate in each brain region and the log plasma insulin level. The reduction in glucose utilization rate was associated with marked increases in serum corticosterone levels (995 +/- 157 vs. 91 +/- 31 nmol/liter in controls, P less than 0.001). Serum potassium was significantly lower in clamped animals (5.2 +/- 0.3 to 5.9 +/- 0.3 mmol/liter) than in controls (7.0 +/- 0.4 mmol/liter, P less than 0.01). However, the inverse correlation between regional brain glucose utilization and log plasma insulin was independent of changes in serum potassium, while there was no independent correlation with serum potassium. The data reveal reduced glucose utilization in specific brain regions in the presence of insulin levels both equal to and above those found in the postabsorptive state and support a direct effect of insulin in suppressing regional brain glucose utilization.

Animals↗
PubMed1985

Rapid bidirectional effects of insulin on hypothalamic noradrenergic and serotoninergic neuronal activity in the rat: role in glucose homeostasis.

Glucose release from the liver is mediated by hypothalamic norepinephrine (NE) neuronal activity, but glucose itself (or a metabolite of it) exerts negative feedback effects on central NE activity. The aim of the present study was to investigate a possible role for insulin in these central glucose homeostatic mechanisms. Computerized gas chromatography-mass spectrometry was used to assess the neuronal activities of hypothalamic NE and serotonin [5-hydroxytryptamine (5-HT)] in rats after acute insulin (2 U/kg) administration. Medial basal hypothalamic NE neuronal activity was assessed by the ratio of 3,4-dihydroxyphenylethyleneglycol to NE. The ratio was suppressed (P less than 0.005) 10 min after insulin administration but rose again to be significantly higher (P less than 0.05) than in saline controls by 30 min and at 45 min post insulin was highly significantly elevated. Hypothalamic 5-HT neuronal activity was assessed by the ratio of 5-hydroxyindoleacetic acid to 5-HT and showed effects opposite to those on NE and was elevated (P less than 0.0005) 10 min post insulin. Significant changes in serum corticosterone and GH levels also occurred after insulin administration, and the changes in these two hormones were positively associated with the changes in hypothalamic neuronal activities of NE and 5-HT, respectively. Serum glucagon levels were found to be significantly elevated in association with the secondary rise in hypothalamic NE activity but did not fall in the 10 min postinsulin phase thus indicating stimulation of pancreatic glucagon release by central NE neuronal pathways. The hypothalamic NE and 5-HT neural responses to a bolus dose of insulin were unaffected by feeding or fasting. These results and evidence that brain glucose utilization is reduced in the immediate postinsulin period suggest that the rapid effects of insulin on hypothalamic NE and 5-HT neuronal activities is a direct one not mediated by stimulation of brain glucose uptake.

Animals↗
PubMed1984

Plasma and erythrocyte choline concentrations in rats following chronic treatment with lithium or choline.

Rats were given daily injections of choline, lithium or lithium plus choline for either 11 or 18 days and red cell choline, glycine and glutathione levels were measured using proton nuclear magnetic resonance spectroscopy. In addition, plasma choline, plasma lithium and red cell lithium levels were measured 4 hr after the last dosage. Choline (1 mmol/kg) alone increased plasma but not red cell choline concentrations. Lithium (0.94 mmol/kg) elevated red cell choline levels but did not affect plasma choline concentrations. In contrast, red cell choline levels were not elevated in rats treated with a higher dose of lithium (1.88 mmol/kg). When choline was given in addition to the lower dose of lithium, a similar accumulation of red cell choline was observed suggesting that the lithium-induced choline accumulation was not enhanced by a greater availability of free choline. No differences were detected in red cell glycine or glutathione levels between any of the treatment groups. Therefore, lithium produced a specific (dose-dependent) accumulation of choline in rat erythrocytes. However, the 100% increase observed in rats was not as marked as the increased red cell choline levels reported in patients maintained on lithium (8 to 10-fold). This discrepancy supports the concept that species differences exist in red cell choline transport or metabolism.

Animals↗
PubMed1983

Effect of guanethidine sympathectomy on intake and body weight of intact and LHA-lesioned rats.

The present study investigated the role of direct sympathetic nervous system innervation of the viscera in the reduced body weight levels maintained by animals bearing lesions of the lateral hypothalamic area (LHA). Adult, male rats with, and without, electrolytic lesions of the (LHA) were treated with guanethidine sulphate (25 mg/kg IP daily for 6 weeks) to produce destruction of the peripheral sympathetic nervous system. LHA-lesioned rats displayed the expected reduced body weight compared to intact rats. Sympathectomy in lesioned rats resulted in an identical pattern of effects to that seen in intact rats. Transitory reductions in intake were effected and weight was significantly depressed by one week of guanethidine treatment. However, weight had recovered to control levels in both intact and lesioned drug-treated groups by the end of the experiment. The reduced body weight level maintained by LHA-lesioned rats was not altered by guanethidine sympathectomy. The major conclusions are (1) the reduced body weights maintained following LHA lesions are not dependent upon an intact sympathetic nervous innervation of visceral organs, and (2) peripheral sympathectomy in intact adult rats has no chronic effects on either body weight or food and water intake.

Animals↗