Effect of exercise training on whole-body insulin sensitivity and responsiveness

1984 ◽  
Vol 56 (5) ◽  
pp. 1217-1222 ◽  
Author(s):  
D. E. James ◽  
E. W. Kraegen ◽  
D. J. Chisholm
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Glucose Utilization ◽  
Insulin Receptors ◽  
Whole Body ◽  
Glucose Disposal ◽  
Significant Shift ◽  
Insulin Levels ◽  
Plasma Insulin Levels

Exercise training causes a decline in basal and glucose-stimulated plasma insulin levels and improves glucose tolerance. Furthermore evidence has been presented for effects on both insulin receptors and postreceptor events. However, it is unclear how these changes affect the in vivo dose-response relationship between insulin levels and whole-body glucose utilization. The aim was to examine the effect of exercise training on this relationship and distinguish between changes in insulin sensitivity and responsiveness. Euglycemic clamps were performed in trained (ET, running 1 h/day for 7 wk), sedentary (CON), and sedentary food-restricted ( SFR ) rats. ET rats showed no increase in maximal net glucose utilization in response to insulin (ET 29.5 +/- 0.6 vs. CON 28.2 +/- 1.5 mg X kg-1 X min-1, NS), whereas insulin sensitivity was increased as indicated by the insulin concentration causing half-maximal stimulation (ED50) (49 +/- 20 for ET and 133 +/- 30 mU/l for CON). Thus 7 wk of moderate exercise training resulted in a significant shift of whole-body insulin sensitivity to place ED50 well within the physiological range of insulin concentrations. This would undoubtedly result in improved glucose disposal in the postprandial state and emphasizes the potential benefit of exercise in obesity and type II diabetes.

In vivo insulin sensitivity in the rat determined by euglycemic clamp

1983 ◽  
Vol 245 (1) ◽  
pp. E1-E7 ◽  
Author(s):  
E. W. Kraegen ◽  
D. E. James ◽  
S. P. Bennett ◽  
D. J. Chisholm
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Porcine Insulin ◽  
Metabolic Clearance ◽  
Conscious Rat ◽  
Insulin Levels ◽  
In Vivo Measurement ◽  
Plasma Insulin Levels

Our aim was to develop the glucose clamp (GC) technique in the conscious rat for assessment of in vivo insulin sensitivity. A 2-h euglycemic GC could be performed in chronically cannulated rats using 625 microliter blood. Overnight-fasted rats were infused with porcine insulin (1.67 mU . kg-1 . h-1). Insulin levels of 41 +/- 2 (SE) mU/liter were produced in rats aged 91 +/- 4 days with a 60- to 120-min glucose infusion rate (GIR60-120) of 10.6 +/- 0.6 mg . kg-1 . min-1 (n = 9) during euglycemia. GIR60-120 was significantly (P less than 0.025) reduced in rats aged greater than 130 days (mean, 169 +/- 16 days) to 7.7 +/- 1.2 mg . kg-1 . min-1 (n = 7). Metabolic clearance rate of porcine insulin (46 +/- 3 ml . kg-1 . min-1) and GIR60-120 compared with plateau plasma insulin levels are higher than values reported in humans. The latter may be due to suppression of a higher basal hepatic glucose production or increased potency of porcine compared with native insulin. We conclude that the GC can be accomplished in the rat. When combined with tracer administration and subsequent killing, it should provide a quantitative in vivo measurement of insulin sensitivity in individual tissues.

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

1985 ◽  
Vol 248 (5) ◽  
pp. E567-E574 ◽  
Author(s):  
D. E. James ◽  
A. B. Jenkins ◽  
E. W. Kraegen
Keyword(s):  
Insulin Sensitivity ◽  
Glycogen Content ◽  
Glycogen Synthesis ◽  
Relative Proportion ◽  
Glycogen Storage ◽  
Whole Body ◽  
Glucose Disposal ◽  
Maximal Effect ◽  
Euglycemic Hyperinsulinemic Clamp

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.

Increased in vivo glucose utilization in 30-day-old obese Zucker rat: role of white adipose tissue

1988 ◽  
Vol 254 (3) ◽  
pp. E342-E348 ◽  
Author(s):  
S. Krief ◽  
R. Bazin ◽  
F. Dupuy ◽  
M. Lavau
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Utilization ◽  
Whole Body ◽  
Glucose Disposal ◽  
Zucker Rats ◽  
Brown Adipose ◽  
Obese Rats ◽  
Proximal Intestine

In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by [3-3H]glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia (140 vs. 55 microU/ml). In obese compared with lean rats, tissue glucose uptake (assessed by the 2-deoxyglucose technique) was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart, in proximal intestine, and in total muscular mass of limbs. Our data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake.

Impact of variable insulinemia and glycemia on in vivo glycolysis and glucose storage in dogs

1994 ◽  
Vol 266 (1) ◽  
pp. E62-E71 ◽  
Author(s):  
M. J. Christopher ◽  
C. Rantzau ◽  
G. M. Ward ◽  
F. P. Alford
Keyword(s):  
Glucose Uptake ◽  
Tritiated Water ◽  
Insulin Level ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glycolytic Flux ◽  
Insulin Levels ◽  
Glucose Storage ◽  
The Impact

To determine the impact of variable plasma insulin concentrations and glycemia on the partitioning of whole body glucose metabolism between glycolysis and glucose storage, we estimated endogenous hepatic glucose production and rates of in vivo glycolytic flux (GF) and glucose storage (GS) in six normal dogs from the generation of plasma tritiated water (3H2O) and [3-3H]glucose specific activity during 150 min of somatostatin euglycemic (E) and hyperglycemic (H) clamps at hypoinsulinemic, basal, intermediate, and high insulin levels. During both E and H clamps, overall rates of GF and GS increased with the rising insulin levels, but the relative contributions to in vivo glucose disposal of GF decreased, whereas GS rose progressively with increasing insulin levels. The relative contribution of GS during H to overall glucose disposal was greater at the lower insulin level. In addition, in absolute terms, GF and GS were significantly higher (P < 0.05) during H than during E at all insulin levels. Moreover, the incremental rise in GF induced by H was equal for the low to intermediate insulin levels tested, independent of the prevailing free fatty acid (FFA) levels. However, when whole body glucose disposal rates were matched, GF and GS rates were independent of the coexisting glycemia, insulin, and/or FFA levels. We conclude that 1) insulin has a major impact on the intracellular fate of infused glucose, with a lesser but significant effect of hyperglycemia per se on these processes; 2) the magnitude of the hyperglycemia-induced increase in GF is independent of the prevailing insulin level from low to intermediate levels; and 3) in vivo GF and GS are dependent on the net rate of glucose uptake into cells but independent of absolute FFA levels or whether glucose uptake is stimulated by raised insulin or glucose levels.

Antisense oligonucleotides against the lipid phosphatase SHIP2 improve muscle insulin sensitivity in a dietary rat model of the metabolic syndrome

2007 ◽  
Vol 292 (6) ◽  
pp. E1871-E1878 ◽  
Author(s):  
Roland Buettner ◽  
Iris Ottinger ◽  
Christiane Gerhardt-Salbert ◽  
Christian E. Wrede ◽  
Jürgen Schölmerich ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Sensitivity ◽  
Protein Content ◽  
Insulin Action ◽  
Whole Body ◽  
Glucose Disposal ◽  
Standard Diet ◽  
The Metabolic Syndrome ◽  
Lipid Phosphatase

The lipid phosphatase SH2 domain-containing lipid phosphatase (SHIP2) has been implicated in the regulation of insulin sensitivity, but its role in the therapy of insulin-resistant states remains to be defined. Here, we examined the effects of an antisense oligonucleotide (AS) therapy directed against SHIP2 on whole body insulin sensitivity and insulin action in liver and muscle tissue in a dietary rodent model of the metabolic syndrome, the high-fat-fed (HF) rat. Whole body insulin sensitivity was examined in vivo by insulin tolerance tests before and after the intraperitoneal application of an AS directed against SHIP2 (HF-SHIP2-AS) or a control AS (HF-Con-AS) in HF rats. Insulin action in liver and muscle was assayed by measuring the activation of protein kinase B (Akt) and insulin receptor substrate (IRS)-1/2 after a portal venous insulin bolus. SHIP2 mRNA and protein content were quantified in these tissues by real-time PCR and immunoblotting, respectively. In HF-SHIP2-AS, whole body glucose disposal after an insulin bolus was markedly elevated compared with HF-Con-AS. In liver, insulin activated Akt similarly in both groups. In muscle, insulin did not clearly activate Akt in HF-Con-AS animals, whereas insulin-induced Akt phosphorylation was sustained in SHIP2-AS-treated rats. IRS-1/2 activation did not differ between the experimental groups. SHIP2 mRNA and protein content were markedly reduced only in muscle. In standard diet-fed controls, SHIP2-AS reduced SHIP2 protein levels in liver and muscle, but it had no significant effect on insulin sensitivity. We conclude that treatment with SHIP2-AS can rapidly improve muscle insulin sensitivity in dietary insulin resistance. The long-term feasability of such a strategy should be examined further.

Mechanisms of acute hyperinsulinemia after Kupffer cell phagocytosis

1980 ◽  
Vol 238 (3) ◽  
pp. E276-E283 ◽  
Author(s):  
R. P. Cornell
Keyword(s):  
Insulin Secretion ◽  
Kupffer Cells ◽  
Plasma Insulin ◽  
Insulin Receptors ◽  
Insulin Levels ◽  
Peripheral Plasma ◽  
Pancreatic Insulin ◽  
Plasma Insulin Levels ◽  
Hepatic Insulin Extraction

Blockade of hepatic Kupffer cells by prior phagocytosis of a variety of particulate materials caused acute hyperinsulinemia in glucose-stimulated fasted rats under pentobarbital anesthesia. At 4-h postblockade a 125-250% increase in peripheral plasma insulin levels occurred due to a combination of enhanced pancreatic insulin secretion and depressed hepatic insulin extraction. Enhanced pancreatic insulin secretion was confirmed by a 36-54% elevation of portal venous insulin levels. Depressed hepatic insulin extraction was indicated by a 37-47% reduction in insulin uptake by in situ perfused livers as well as alterations in portal-hepatic venous insulin differences and intravenous insulin tolerance tests in vivo. All parameters began to return toward control values at 24 and 48 h postblockade. Return was slow after inert carbon phagocytosis and rapid after degradable bacteria phagocytosis. Peripheral plasma insulin levels were very highly correlated with glucose clearance rates in all groups both control and experimental. Mechanisms are proposed to explain these findings based on the release of lysosomal enzymes and endogenous pyrogens by phagocytizing Kupffer cells as well as the presence of insulin receptors on hepatocytes and Kupffer cells.

Insulin-independent glucose uptake in growth hormone treated dairy cows

1998 ◽  
Vol 65 (3) ◽  
pp. 423-431 ◽  
Author(s):  
MICHAEL T. ROSE ◽  
FUMIAKI ITOH ◽  
MITSUTO MATSUMOTO ◽  
YUJI TAKAHASHI ◽  
YOSHIAKI OBARA
Keyword(s):  
Growth Hormone ◽  
Dairy Cows ◽  
Glucose Uptake ◽  
Plasma Insulin ◽  
Whole Body ◽  
Glucose Disposal ◽  
Glucose Turnover ◽  
Insulin Levels ◽  
Elevated Glucose ◽  
Plasma Insulin Levels

Our aim was to determine the effect of growth hormone on non-insulin-mediated glucose disposal in lactating dairy cows. Following 5 d of subcutaneous injections of either saline or growth hormone, insulin, somatostatin or insulin plus somatostatin were infused for 2 h each, in a series of experiments. Coincident with this, unlabelled glucose was infused at a variable rate to maintain a constant plasma glucose concentration. Glucose, doubly labelled with deuterium, was also infused for the calculations of glucose turnover. Plasma insulin levels were reduced to nearly zero by the infusion of somatostatin; under such conditions whole body glucose disposal should be non-insulin-mediated. Dairy cows treated with growth hormone, which had significantly increased milk yields on the day before the experimental infusions, did not have different levels of whole body non-insulin-mediated glucose disposal when expressed in absolute terms. Growth hormone did not affect non-mammary non-insulin-mediated glucose uptake estimated by calculation. Growth hormone significantly inhibited insulin-mediated glucose uptake when plasma insulin levels were elevated. Glucose uptake during insulin plus somatostatin infusion was not significantly different from that of the insulin only infusion.

Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

1986 ◽  
Vol 250 (5) ◽  
pp. E570-E575
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
S. A. Kaplan ◽  
E. Sternlicht
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Binding ◽  
Whole Body ◽  
Rat Skeletal Muscle ◽  
Binding Studies ◽  
Muscle Enzyme ◽  
Intravenous Glucose ◽  
High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

scholarly journals Prep1 Deficiency Induces Protection from Diabetes and Increased Insulin Sensitivity through a p160-Mediated Mechanism

2008 ◽  
Vol 28 (18) ◽  
pp. 5634-5645 ◽  
Author(s):  
Francesco Oriente ◽  
Luis Cesar Fernandez Diaz ◽  
Claudia Miele ◽  
Salvatore Iovino ◽  
Silvia Mori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Normal Glucose Tolerance ◽  
Glucose Disposal ◽  
Protein Levels ◽  
Normal Glucose ◽  
Enhanced Expression ◽  
The Stability

ABSTRACT We have examined glucose homeostasis in mice hypomorphic for the homeotic transcription factor gene Prep1. Prep1-hypomorphic (Prep1 i / i ) mice exhibit an absolute reduction in circulating insulin levels but normal glucose tolerance. In addition, these mice exhibit protection from streptozotocin-induced diabetes and enhanced insulin sensitivity with improved glucose uptake and insulin-dependent glucose disposal by skeletal muscle. This muscle phenotype does not depend on reduced expression of the known Prep1 transcription partner, Pbx1. Instead, in Prep1 i / i muscle, we find normal Pbx1 but reduced levels of the recently identified novel Prep1 interactor p160. Consistent with this reduction, we find a muscle-selective increase in mRNA and protein levels of PGC-1α, accompanied by enhanced expression of the GLUT4 transporter, responsible for insulin-stimulated glucose uptake in muscle. Indeed, using L6 skeletal muscle cells, we induced the opposite effects by overexpressing Prep1 or p160, but not Pbx1. In vivo skeletal muscle delivery of p160 cDNA in Prep1 i / i mice also reverses the molecular phenotype. Finally, we show that Prep1 controls the stability of the p160 protein. We conclude that Prep1 controls insulin sensitivity through the p160-GLUT4 pathway.

Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus

1992 ◽  
Vol 127 (4) ◽  
pp. 344-350 ◽  
Author(s):  
Allan A Vaag ◽  
Henning Beck-Nielsen
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Treatment Period ◽  
Blood Glucose Control ◽  
Glucose Disposal ◽  
Prolonged Treatment ◽  
Double Blind Study ◽  
Glucose And Lipid Metabolism ◽  
Fasting Plasma

The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg×3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterifled fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34±0.09 vs 0.66±0.09 mmol/l; p<0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367±59 vs 392±66 mg·m−2·min−1, NS; both p<0.05 vs placebo glucose disposal) (267±44 mg·m−2·min−1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis.

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