Biomedical subjects

D E James

Publications and source records attributed to D E James.

At least 109 records · Page 6Linked to original sources

PubMed1989

Chronic exercise compensates for insulin resistance induced by a high-fat diet in rats.

We examined whether chronic exercise prevents insulin resistance developing in the high-fat-fed (HFF) rat, a model that otherwise develops profound peripheral insulin resistance. Insulin action (euglycemic clamp plus 2-[3H]deoxy-D-glucose-[14C]glucose tracer technique) was examined after 3 wk in sedentary control and sedentary or wheel cage exercise-trained HFF rats. At the whole body level, a reduction in peripheral insulin potency in HFF rats was prevented by concomitant chronic exercise; the 30-40% reduction in insulin-stimulated whole body net glucose utilization in sedentary HFF rats was abolished. Responses in individual muscles, however, suggested that the chronic exercise effect may be a compensation for, rather than a correction of insulin resistance induced by a high-fat diet; in six of eight muscles examined it produced an upward additive shift rather than a left shift in insulin dose response. Chronic exercise increased both muscle glycolytic flux and glycogen storage rates in the HFF rats, suggesting that glucose transport may be involved. We conclude that increased physical activity is beneficial in counteracting high-fat diet-induced insulin resistance. Different processes appear to be involved in the development of diet-induced insulin resistance in muscle and its amelioration by regular exercise.

Animals↗

PubMed1988

Fractionation of endocytic vesicles and glucose-transporter-containing vesicles in rat adipocytes.

We subfractionated intracellular vesicles from rat adipocytes in order to examine the subcellular distribution of endocytic vesicles or endosomes with respect to insulin-regulatable glucose-transporter (GT)-containing vesicles [James, Lederman & Pilch (1987) J. Biol. Chem. 262, 11817-11824]. Vesicles mediating fluid-phase endocytosis sedimented as a single major peak of greater density than the single distinct peak of GT-containing vesicles. This difference was also apparent during cellular insulin exposure and after insulin removal. Endocytosis of insulin and IGF (insulin-like growth factor) II was also examined. In sucrose gradients, IGF II-containing vesicles were less dense than those containing internalized insulin. Receptor-mediated endocytic vesicles were distinct from fluid-phase endocytic vesicles, but overlapped with the GT-containing vesicles. Vesicles containing internalized ligand were further fractionated by agarose-gel electrophoresis after various times of internalization. At least three different vesicle subpopulations containing the iodinated ligands were resolved after 5 min of internalization. Endocytic vesicles containing rapidly internalized insulin (1.5 min at 37 degrees C) consistently co-migrated with GT-containing vesicles. These data indicate that fluid-phase and receptor-mediated endocytosis occur via different pathways in adipocytes. Furthermore, whereas the intracellular GT-containing vesicles are distinct from fluid-phase vesicles, a rapidly labelled pool of insulin-containing vesicles consistently co-fractionated with GT-containing vesicles when separation techniques based on size, density and charge were used. This suggests that the insulin receptor may directly interact with the intracellular GT-containing vesicles after insulin-induced endocytosis.

Adipose Tissue↗

PubMed1988

Insulin-like growth factor I binding and receptor kinase in red and white muscle.

IGF-I receptors were partially purified from red and white skeletal muscle by lectin-affinity chromatography and the resultant fraction was depleted of insulin receptors by insulin affinity chromatography. Equilibrium binding of 125I-IGF-I to receptor preparations from red and white muscle yielded identical Scatchard plots. The integrity of the IGF-I receptor preparation in the two fiber types was identical as determined by affinity cross-linking. The tyrosine kinase activity of the receptor from red muscle was 2-3-fold more active towards exogenous substrates in both the basal and ligand-activated states as compared to white muscle. These data show that there is IGF-I-dependent kinase activity intrinsic to IGF-I receptors from skeletal muscle, and suggest that identical cellular factors may regulate the kinase activity of insulin and IGF-I receptors in a parallel manner in vivo.

Animals↗

PubMed1988

Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein.

At least three different glucose transport systems exist in mammalian cells. These are: (1) the constitutively active, facilitative carrier characteristic of human erythrocytes, Hep G2 (ref. 2) cells and rat brain; (2) the Na-dependent active transporter of kidney and small intestine; and (3) the facilitative carrier of rat liver (B. Thorens and H. F. Lodish, personal communication). A fourth possible glucose transport system is the insulin-dependent carrier that may be specific to muscle and adipose tissue. This transporter resides primarily in an intracellular compartment in resting cells from where it translocates to the cell surface upon cellular insulin exposure. This raises the question of whether hormonal regulation of glucose transport is conferred by virtue of a tissue-specific signalling mechanism or a tissue-specific glucose transporter. Here we present data supporting the latter concept based upon a monoclonal antibody against the fat cell glucose transporter that identifies a unique, insulin-regulatable glucose transport protein in muscle and adipose tissue.

Adipose Tissue↗

PubMed1987

Purification of insulin-dependent exocytic vesicles containing the glucose transporter.

In muscle and fat, insulin causes the cellular redistribution of glucose transporters and insulin-like growth factor II receptors from an intracellular pool of membranes (low density microsomes) to the plasma membrane. This translocation is a major mechanism by which insulin stimulates cellular glucose uptake. Our aim was to purify and characterize the insulin-regulatable exocytic intracellular membranes that are enriched in glucose transporter. Low density microsome and plasma membrane fractions were isolated from basal and insulin-stimulated rat adipocytes by differential centrifugation. In cells exposed to insulin, glucose transporters were decreased in the low density microsomes and correspondingly increased in the plasma membranes as determined by immunoblotting and cytochalasin B binding. Low density microsomes were further fractionated by sucrose density gradient centrifugation. Membranes containing glucose transporters were separated from the major protein-containing peaks and from plasma membranes, Golgi, and endoplasmic reticulum. Further fractionation was achieved by agarose gel electrophoresis. Overall, the intracellular membranes enriched in transporter were purified 9-fold compared to low density microsomes. These purified membranes had the following characteristics: 1) uniformly sized vesicles, diameter 60-100 nm; 2) insulin-regulatable protein composition, one constituent being an Mr 43,000 protein that co-migrated with immunoblotted glucose transporters; 3) enrichment in insulin-like growth factor II receptors, but of a lesser degree than the enrichment in transporters. Thus, using a three-step procedure, insulin-sensitive translocatable vesicles from adipocytes have been highly purified. These are similar in size and density to endosomes, and the glucose transporter is a major constituent of this distinct vesicle population.

Adipose Tissue↗

PubMed1986

Intrinsic differences of insulin receptor kinase activity in red and white muscle.

The sensitivity and responsiveness of glucose uptake and glycogen synthesis to insulin are 3-4-fold greater in red than in white skeletal muscle (James, D. E., Jenkins, A. B., and Kraegen, E. W. (1985) Am. J. Physiol. 248, E567-E574). In the present study, the insulin receptor tyrosine kinase activity has been examined in red and white muscle of rats. Partially purified insulin receptors were obtained from muscle following solubilization in detergent, ultracentrifugation, and lectin affinity chromatography. Total insulin receptor number per gram of tissue was slightly higher in red (30%) than in white muscle. In contrast, basal and insulin-stimulated autophosphorylation, normalized for receptor number, were 2.3-fold higher in red muscle. A similar difference was observed in the ability of partially purified receptors to phosphorylate the exogenous substrate polyglutamate/tyrosine. The integrity of the insulin receptor preparation in the two fiber types was identical as determined by affinity cross-linking of [125I-TyrB26]insulin to the receptor. Mixing partially purified receptors from red and white muscle resulted in an additive response for exogenous substrate phosphorylation, suggesting that the difference in tyrosine kinase activity was not due to the presence of an inhibitor or activator. The results suggest that there are differences in the insulin receptors of red and white muscles that lead to discordance in their basal and insulin-stimulated intrinsic tyrosine kinase activity. The correlation between these differences and insulin action in red and white muscle supports the concept that the insulin receptor tyrosine kinase activity is involved in the initiation of insulin action.

Animals↗

PubMed1986

In vivo glucose metabolism in individual tissues of the rat. Interaction between epinephrine and insulin.

The interaction between epinephrine and insulin in modulating in vivo glucose metabolism within individual tissues of the body has not previously been examined. This was investigated using the euglycemic hyperinsulinemic (120 milliunits/liter) clamp combined with administration of [3H]2-deoxyglucose and D-[U-14C]glucose. Epinephrine produced whole body insulin resistance due to increased hepatic glucose output and reduced peripheral glucose disposal. Despite elevated insulin levels liver glycogen content was reduced by 50% during epinephrine infusion (5 nM). However, this effect was transient, occurring predominantly during the initial 60 min of study. These effects were prevented during beta-adrenergic blockade with propranolol and potentiated during alpha 1-adrenergic blockade with prazosin. The most significant effect of epinephrine in peripheral tissues was increased glycogenolysis in both oxidative and glycolytic skeletal muscle. A significant reduction in insulin-mediated [3H]2-deoxyglucose uptake (30%) was evident in 5 of 9 muscles tested during epinephrine infusion. This effect was most pronounced in the more insulin-sensitive oxidative muscles. The latter effect was probably indirectly mediated via increased glycogenolysis--increased accumulation of metabolites--inhibition of hexokinase. In addition, it is evident that insulin-mediated glycogen synthesis occurred during epinephrine infusion. All effects of epinephrine on muscle glucose metabolism were prevented by propranolol but not prazosin. Similar effects to that observed in muscle were not evident in adipose tissue. It is concluded that epinephrine may override many of the actions of insulin in vivo, and most of these effects are mediated via the beta-adrenergic receptor. In the intact rat there may be a complex interaction between alpha- and beta-adrenergic effects in regulating hepatic glucose output.

Animals↗

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

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

Exercise-induced hepatic glucose output is precisely sensitive to the rate of systemic glucose supply.

It has previously been established that a glucose infusion causing hyperglycemia and alterations in the levels of glucoregulatory hormones suppresses the exercise-induced increment in systemic glucose appearance (Ra). In an attempt to define the mechanisms responsible for this suppression of Ra, five normal subjects were exercised for 60 minutes on a bicycle ergometer at 60% Vo2 max on two occasions. On both occasions Ra was measured by a nonsteady state technique using a constant infusion of 3-3H-glucose. On the second occasion, an IV infusion of glucose was administered in a stepwise fashion to simulate in timing and magnitude the measured Ra response from the first study. Endogenous glucose production in the second study, estimated by subtracting the amount of glucose infused from the measured Ra response, did not increase above basal (endogenous glucose output response = 0.5 +/- 8.4 mmol/60 min v control study 60.2 +/- 6.6 mmol/60 min, P less than 0.01). The suppression of Ra was associated with a small but significant effect on venous plasma glucose (increment above basal less than 0.3 mmol/L, P less than 0.05) and a significant change in glucose metabolic clearance rate during the second 30 minutes of exercise. Serum insulin, C-peptide, cortisol, growth hormone, and plasma glucagon responses to exercise were not significantly affected by glucose infusion and the ratio of circulating insulin to glucagon was also not affected. These results indicate that hepatic glucose output during exercise is precisely sensitive to glucose supply. The feedback inhibition is presumably mediated by a small increase in plasma glucose but cannot readily be accounted for by changes in glucoregulatory hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1985

In vivo dose response curves of insulin action in heart: anomalous effects at high insulin doses.

The euglycaemic hyperinsulaemic clamp technique in conscious unrestrained rats was used to compile insulin dose response curves of glucose metabolism in the heart in vivo. An estimate of heart glucose uptake (Rg') was obtained using [3H]-2-deoxyglucose and glucose disposal was examined by measuring cardiac glycogen content. Elevation of insulin from 29 to 54 mU/l resulted in a significant increase in Rg' in heart from 41 +/- 6 to 77 +/- 4 mumol/100 g/min (P less than 0.01) with no effect on glycogen content. This is consistent with increased glucose oxidation. At 150 mU/l of insulin both Rg' and glycogen synthesis were increased. Glycogen content increased from 18.5 +/- 1.7 mumol/g under basal conditions to 27.9 +/- 1.6 mumol/g with insulin. However, at subsequent insulin doses producing plasma levels exceeding 600 mU/l there was an anomalous reversal of Rg' back to basal levels while glycogen content was significantly elevated (2.4-fold, P less than 0.01). This effect may be related to feedback inhibition of tissue glycogen on glucose transport or to accumulation of tissue metabolites such as glucose-6-phosphate. The dose response curve for insulin stimulated Rg' in heart does not resemble either the whole body glucose utilization curve or that in individual skeletal muscles.

Animals↗

PubMed1985

Dose-response curves for in vivo insulin sensitivity in individual tissues in rats.

A technique is described for examining in vivo insulin action on glucose utilization in individual tissues in the intact conscious rat. Indices of tissue glucose metabolic rate Rg' and of the percentage of total glucose uptake incorporated into specific storage products (Cf) are derived from tissue analysis after bolus administration of 2-[3H]deoxyglucose and [14C]glucose during the plateau phase of the euglycemic clamp. The effects of insulin elevation have been examined in several tissues. Rg' in diaphragm increased 10-fold over basal (maximal) with a half-maximal sensitivity (ED50) of 150 mU/l. This was similar to the ED50 for net whole body glucose utilization of 133 mU/l. In adipose tissue Rg' increased by twofold and Cf into lipids by sixfold; both were near maximal at 150 mU/l (ED50 of 60 mU/l). A small but significant insulin effect (Rg' increased 2-fold) was found in lung. Insulin did not significantly increase Cf into total liver lipids or glycogen. The methodology described here significantly increases the usefulness of the glucose clamp technique in the study of insulin action. Dose-response curves for insulin action during the euglycemic clamp vary considerably among different target tissues in the rat.

Adipose Tissue↗

PubMed1985

Heterogeneity of insulin action in individual muscles in vivo: euglycemic clamp studies in rats.

The euglycemic hyperinsulinemic clamp technique in conscious unrestrained rats was used to examine the effect of insulin on glucose metabolism in metabolically distinct skeletal muscle in vivo. Tissue glucose metabolic rate (R'g) was estimated using 2-[3H]-deoxyglucose, and glucose disposal was examined by measuring glycogen content and [14C]glucose incorporation into glycogen in four different muscles. Insulin sensitivity varied among different muscle types in that the insulin concentration required for half-maximal stimulation of R'g was 80, 150, 280, and 320 mU/1 for soleus (SOL), red gastrocnemius (RG), white gastrocnemius (WG), and extensor digitorum longus, respectively. There were similar relative differences in the maximal effect of insulin on R'g in these muscles. Maximal insulin stimulation almost doubled muscle glycogen content in RG and SOL, whereas there was no change in WG. The relationship between R'g and glycogen synthesis indicated that increased glucose uptake resulted predominantly in glycogen storage. There was an excellent relationship between maximal R'g and blood flow in different muscles. We conclude that there is marked heterogeneity in insulin sensitivity and responsiveness among muscles of different fiber composition. Insulin-induced increases in total peripheral glucose disposal occur predominantly in muscles containing a high proportion of oxidative fibers. Therefore the relative proportion of oxidative to glycolytic muscle fibers may be important factors in determining whole body insulin sensitivity.

Animals↗

PubMed1985

Muscle glucose metabolism in exercising rats: comparison with insulin stimulation.

We describe here a technique using bolus 2-[3H]deoxyglucose (2-[3H]DG) administration for estimating the glucose metabolic rate (R'g) in individual tissues of the rat during exercise. After 50 min of treadmill running at a moderate work load various tissues were analyzed for accumulation of phosphorylated 2-[3H]DG and/or glycogen mass. There was considerable heterogeneity in R'g in response to exercise among different muscles, despite similar basal values. R'g increased 32-fold above basal in soleus (to 90.4 +/- 5.7 mumol X 100 g-1 X min-1), 42-fold in red gastrocnemius (to 71.2 +/- 1.6), 5-fold in white gastrocnemius (to 7.0 +/- 0.8), and 2-fold in extensor digitorum longus (to 4.1 +/- 1.0) during exercise. There was a close relationship between muscle glycogen depletion and R'g within different muscles. In view of the magnitude of the increase in R'g during exercise, this method provides a very sensitive index of muscle fiber recruitment during exercise. The pattern of exercise-stimulated R'g in muscles of different fiber composition was similar to that seen with insulin stimulation. However, moderate exercise alone produced increments in R'g (soleus and red gastrocnemius) that were significantly higher (P less than 0.005) than that observed during maximal insulin stimulation even though whole body glucose utilization was slightly higher during maximal insulin stimulation. These data emphasize the heterogeneity of the response in different muscles during exercise and suggest that intracellular events beyond glucose transport may be rate limiting under the influence of one or both of these stimuli.

Animals↗

PubMed1985

Effects of exercise training on in vivo insulin action in individual tissues of the rat.

It has previously been suggested that exercise training leads to increased whole body insulin sensitivity. However, the specific tissues and metabolic pathways involved have not been examined in vivo. By combining the euglycemic clamp with administration of glucose tracers, [3H]2-deoxyglucose (2DG), [14C]glucose, and [3H]glucose, in vivo insulin action at the whole body level and within individual tissues has been assessed in exercise-trained (ET, running 1 h/d for 7 wk) and sedentary control rats at four insulin doses. Whole body insulin sensitivity was significantly increased in ET. In addition, the skeletal muscles, soleus, red and white gastrocnemius, extensor digitorum longus (EDL), and diaphragm all showed increased sensitivity of insulin-stimulated 2DG uptake with training. With the exception of EDL, no significant difference in insulin-mediated glycogen synthesis between control and ET could be found. Therefore, the increased insulin-induced 2DG uptake observed in muscle following training is apparently directed towards glucose oxidation. In ET animals, adipose tissue exhibited a significant increase in insulin-mediated 2DG uptake and [14C]glucose incorporation into free fatty acids but there was no difference from control in any parameters measured in lung or liver. EDL and white gastrocnemius, which are not primarily involved during exercise of this type, also demonstrated increased insulin sensitivity following training. In conclusion, exercise training results in a marked increase in whole body insulin sensitivity related mainly to increased glucose oxidation in skeletal muscle. This effect may be mediated by systemic as well as local factors and is likely to be of therapeutic value in pathological conditions exhibiting insulin resistance.

Adipose Tissue↗

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

Time dependence of insulin action in muscle and adipose tissue in the rat in vivo. An increasing response in adipose tissue with time.

The relative time dependency of enhancement of glucose metabolism by insulin in individual tissues has not been examined previously in vivo. Using the glucose clamp technique in the rat combined with radiolabeled 2-deoxyglucose (3H or 14C-2DG) administration, we have estimated a glucose metabolic index (Rg') in major insulin-sensitive tissues at two different times (between 40-55 min and 80-95 min) after onset of hyperinsulinemia (insulin levels of approximately 130 mU/L). At the completion of the clamp (125 min), eight different skeletal muscles and three different adipose tissue beds were rapidly removed for estimation of Rg', based on the accumulation of intracellular tracer 2DG-6-phosphate (2DGP). Insulin-stimulated Rg' was 60-70% higher at 80-95 min than at 40-55 min after elevation of insulin levels in all three adipose tissue beds (P less than 0.01). In contrast, insulin-stimulated whole body glucose utilization and Rg' in all skeletal muscles were not significantly different at these two times. The constancy of insulin action in skeletal muscles during the 2-h euglycemic clamp, as determined in these studies, does not support the concept that the glucose clamp represents an integral of many rapidly changing individual tissue responses. In conclusion, while the amount of insulin-stimulated glucose uptake in adipose tissue is low compared with muscle, the fraction increases with duration of insulin elevation. This effect may have significant implications in hyperinsulinemic states.

Adipose Tissue↗