scholarly journals Insulin resistance of hind-limb tissues in vivo in lactating sheep

1990 ◽  
Vol 270 (3) ◽  
pp. 783-786 ◽  
Author(s):  
R G Vernon ◽  
A Faulkner ◽  
W W Hay ◽  
D T Calvert ◽  
D J Flint
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mammary Gland ◽  
Hind Limb ◽  
Insulin Infusion ◽  
Plasma Concentrations ◽  
Plasma Insulin Concentration ◽  
Esterified Fatty Acids ◽  
Beta Hydroxybutyrate

1. The effects of varying the plasma insulin concentration by infusion while maintaining euglycaemia by infusion of glucose on nutrient arterio-venous differences across the hind-limb and mammary gland in lactating and non-lactating sheep were investigated. 2. Insulin infusion increased the glucose arterio-venous difference across the hind-limb; this effect of insulin was decreased by lactation, suggesting that lactation induces insulin resistance in skeletal muscle. 3. Lactation increased but insulin infusion decreased the plasma concentrations of acetate, beta-hydroxybutyrate and non-esterified fatty acids. 4. Insulin infusion decreased the arterio-venous differences of acetate and hydroxybutyrate across the hind-limb; this effect of insulin is probably indirect, resulting from the decrease in plasma concentrations of these metabolites. 5. Infusion of insulin had no effect on the glucose arterio-venous difference across the mammary gland, but did decrease the oxygen arterio-venous difference. 6. The results suggest that lactation results in insulin resistance in skeletal muscle, at least with respect to glucose utilization; this should facilitate the preferential utilization of glucose by the mammary gland.

Postprandial Substrate Deposition in Human Forearm and Adipose Tissues in Vivo

1990 ◽  
Vol 79 (4) ◽  
pp. 339-348 ◽  
Author(s):  
S. W. Coppack ◽  
R. M. Fisher ◽  
G. F. Gibbons ◽  
S. M. Humphreys ◽  
M. J. McDonough ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Carbon Balance ◽  
Plasma Concentrations ◽  
Normal Subjects ◽  
Esterified Fatty Acids ◽  
Positive Balance ◽  
A Minor

1. Substrate movements in forearm muscle and subcutaneous adipose tissue were studied, by measurement of arteriovenous differences and blood flow, in seven normal subjects after an overnight fast and then for 6 h after ingestion of a mixed meal. Overall substrate balances were examined in terms of the flux of gram-atoms of carbon. 2. As found previously, the forearm was approximately in carbon balance (import equal to export) after the overnight fast, whereas adipose tissue was a net exporter of carbon, mainly in the form of non-esterified fatty acids. 3. After the meal, arterialized plasma concentrations of glucose and lactate rose sharply (peak at 60 min), whereas those of non-esterified fatty acids and glycerol fell (nadir at 60–120 min). Plasma triacylglycerol concentrations rose slowly to peak at 240 min; much of this rise was accounted for by a rise in the chylomicron fraction. 4. Both tissues took up glucose at an increased rate after the meal. Release of non-esterified fatty acids and glycerol from adipose tissue was suppressed. Clearance of triacylglycerol by both tissues increased after the meal, but was more marked in adipose tissue, where the fractional extraction of chylomicron-triacylglycerol reached 44% at 240 min. 5. The forearm rapidly became a considerable net importer of carbon, and remained so until 6 h after the meal when it was again in approximate carbon balance. Glucose uptake dominated the forearm carbon balance. Adipose tissue was a net importer of carbon from 30 min until 5 h after the meal and then reverted to net export. Clearance of triacylglycerol carbon made the largest contribution to this positive balance, but towards the end of the study this was increasingly counterbalanced by simultaneous non-esterified fatty acid release. 6. Skeletal muscle plays a major role, and adipose tissue a minor one, in the disposal of ingested carbohydrate; adipose tissue plays a major role and skeletal muscle a minor one in clearance of dietary-derived triacylglycerol. The role of adipose tissue lipoprotein lipase is not, however, simply the uptake of triacylglycerol for storage within the tissue; rather, it appears to play a central role in the distribution of dietary-derived lipid energy.

scholarly journals Insulin Infusion is Linked to Increased NPPC Expression in Muscle and Plasma C-type Natriuretic Peptide in Male Dogs

2021 ◽  
Author(s):  
Justin M Gregory ◽  
Guillaume Kraft ◽  
Ben Farmer ◽  
Marta S Smith ◽  
David C LaNeve ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Rna Sequencing ◽  
Natriuretic Peptide ◽  
Insulin Infusion ◽  
Plasma Concentrations ◽  
Sequencing Data ◽  
Plasma Insulin Concentration ◽  
Skeletal Muscle Biopsy ◽  
Vascular Bed ◽  
Arterial Plasma

Abstract The purpose of this study was to assess insulin-stimulated gene expression in canine skeletal muscle with a particular focus on NPPC, the gene that encodes C-type natriuretic peptide, a key hormonal regulator of cardiometabolic function. Four conscious canines underwent hyperinsulinemic, euglycemic clamp studies. Skeletal muscle biopsy and arterial plasma samples were collected under basal and insulin-stimulated conditions. Bulk RNA sequencing of muscle tissue was performed to identify differentially expressed genes between these two steady-state conditions. Our results showed that NPPC was the most highly expressed gene in skeletal muscle in response to insulin infusion, rising fourfold between basal and insulin-stimulated conditions. In support of our RNA-sequencing data, we found that raising the plasma insulin concentration 15-fold above basal elicited a 2-fold (p = 0.0001) increase in arterial plasma concentrations of N-terminal prohormone C-type natriuretic peptide. Our data suggest insulin may play a role in stimulating secretion of C-type natriuretic peptide by skeletal muscle. In this context, C-type natriuretic peptide may act in a paracrine manner to facilitate muscle-vascular bed crosstalk and potentiate insulin-mediated vasodilation. This could serve to enhance insulin and glucose delivery, particularly in the postprandial absorptive state.

Sepsis-induced changes in in vivo insulin action in diabetic rats

1989 ◽  
Vol 257 (3) ◽  
pp. E301-E308 ◽  
Author(s):  
C. H. Lang ◽  
C. Dobrescu
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Plasma Concentrations ◽  
Diabetic Rats ◽  
Hepatic Insulin Resistance ◽  
Blood Levels ◽  
Euglycemic Hyperinsulinemic Clamp ◽  
Glucose Output

The present study examined whether sepsis exacerbates the diabetes-induced peripheral and hepatic insulin resistance. Vascular catheters were placed in diabetic (70 mg/kg streptozotocin, 4-wk duration) and nondiabetic rats, and sepsis was produced by subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined with the use of [3-3H]glucose initiated 18 h after the first injection of bacteria. Thereafter, in vivo insulin action was assessed with the use of the euglycemic hyperinsulinemic clamp technique. Sepsis in nondiabetic rats produced a 57% reduction in the maximal responsiveness for the insulin-induced increase in total glucose utilization compared with nondiabetic nonseptic animals. Diabetes alone decreased both insulin sensitivity and responsiveness. When the septic insult was superimposed on the diabetic condition, the maximum responsiveness was unchanged compared with non-septic diabetic rats, but the 50% maximally efficient dose was reduced from 817 to 190 microU/ml, suggesting an improvement in insulin sensitivity. Sepsis did not alter the insulin-induced suppression of hepatic glucose output in either nondiabetic or diabetic animals. Sepsis increased the plasma concentrations of epinephrine, norepinephrine, glucagon, and corticosterone in both nondiabetic and diabetic rats; however, the elevation in catecholamines and glucagon was 65 to 250% greater in the diabetic animals. These results indicate that hypermetabolic sepsis produces peripheral insulin resistance in nondiabetic rats but does not worsen the preexisting insulin resistance in diabetic animals, despite the higher prevailing blood levels of glucagon and catecholamines.

scholarly journals Tryptophan and the control of plasma glucose concentrations in the rat

1977 ◽  
Vol 168 (3) ◽  
pp. 495-506 ◽  
Author(s):  
S A Smith ◽  
C I Pogson
Keyword(s):  
Adrenal Glands ◽  
Experimental Diabetes ◽  
Plasma Concentrations ◽  
Hypoglycaemic Effect ◽  
Esterified Fatty Acids ◽  
Tryptophan Metabolites ◽  
The Central Nervous System ◽  
Concentration Changes ◽  
Beta Hydroxybutyrate ◽  
Hydrazinopropionic Acid

1. Injection of L-tryptophan (750 mg/kg body wt.) led to pronounced hypoglycaemia in fed and 48 h-starved rats. 2. The hypoglycaemic effect is blocked by pretreament with p-chlorophenylalanine, compound MK-486 [Carbidopa: L-alpha-(3,4-dihydroxybenzyl)-alpha-hydrazinopropionic acid monohydrate] or methysergide, and potentiated by pargyline. 3. 5-Hydroxy-L-tryptophan is more potent and induces a more rapid hypoglycaemia than does tryptophan. Other tryptophan metabolites were not associated with hypoglycaemia. 4. Adrenalectomy increases, and acute experimental diabetes strongly decreases, the sensitivity of rats to tryptophan induction of hypoglycaemia. Diabetic animals were also insensitive to 5-hydroxytryptophan. 5. Metabolite concentration changes in the livers from tryptophan-treated 48h-starved and diabetic animals were consistent with a rapid inhibition of gluconeogenesis. This did not correlate with the hypoglycaemic response. 6. Tryptophan treatment was associated with a significant increase in the plasma [beta-hydroxybutyrate]/[acetoacetate] ratio; there were no changes in the plasma concentrations of urea, triacyglycerol, non-esterified fatty acids and glycerol. 7. These observations suggest that the hypoglycaemic action of tryptophan is mediated through formation of intracellular 5-hydroxytryptamine, and is unrelated to the inhibition of gluconeogenesis. It is unlikely that this increased synthesis of 5-hydroxytryptamine involves directly either the adrenal glands or the central nervous system.

Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats

1990 ◽  
Vol 79 (2) ◽  
pp. 139-147 ◽  
Author(s):  
M. Salleh M. Ardawi ◽  
Yasir S. Jamal
Keyword(s):  
Skeletal Muscle ◽  
Exchange Rates ◽  
Skeletal Muscles ◽  
Plasma Concentrations ◽  
Maximal Activity ◽  
Glutamine Metabolism ◽  
Dexamethasone Treatment ◽  
Concentration Difference

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment. 2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%). 3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb. 4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls. 5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased. 6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats. 7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.

scholarly journals The Role of TGFβ Ligands and Signalling on Insulin Resistance in Skeletal Muscle in Women With PCOS

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A443-A444
Author(s):  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Rhiannon K Patten ◽  
Andrew J McAinch ◽  
Raymond J Rodgers ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Insulin Signalling ◽  
Signalling Pathway ◽  
Whole Body ◽  
Insulin Signalling Pathway ◽  
Cultured Myotubes ◽  
Tgfβ Superfamily

Abstract Polycystic ovary syndrome (PCOS) is the most common female endocrinopathy affecting metabolic and reproductive health of 8–13% of reproductive-age women. Insulin resistance (IR) appears to underpin the pathophysiology of PCOS and is present in approximately 38–95% of women with PCOS. This underlying IR has been identified as unique from, but synergistic with, obesity-induced IR (1). Skeletal muscle accounts for up to 85% of whole-body insulin-stimulated glucose uptake; however, in PCOS this is reduced by about 27% when assessed by a euglycaemic-hyperinsulinaemic clamp (2). Interestingly, this reduced insulin-stimulated glucose uptake observed in skeletal muscle tissue is not retained in cultured myotubes (3), suggesting that in vivo environmental factors may play a role in this PCOS-specific IR. Yet, the molecular mechanisms regulating IR remain unclear (4). A potential environmental mechanism contributing to the development of peripheral IR may be the extracellular matrix remodelling and aberrant transforming growth factor beta (TGFβ) signalling. Previous work demonstrated that TGFβ superfamily ligands are involved in the increased collagen deposition and fibrotic tissue in the ovaries, and suggested that these ligands may be involved in the metabolic morbidity associated with PCOS (5). In this study, we investigated the effects of TGFβ1 (1, 5 ng/ml), and the Anti-Müllerian hormone (AMH; 5, 10, 30 ng/ml), a TGFβ superfamily ligand elevated in women with PCOS, as causal factors of IR in cultured myotubes from women with PCOS (n=5) and healthy controls (n=5). TGFβ1 did not have a significant effect on insulin signalling but induced expression of some ECM related genes and proteins, and increased glucose uptake via Smad2/3 signalling in myotubes from both groups. Conversely, AMH did not appear to activate the TGFβ/Smad signalling pathway and had no significant impact on insulin signalling or glucose uptake in any of the groups. In conclusion, these findings suggest that TGFβ1, but not AMH, may play a role in skeletal muscle ECM remodelling/fibrosis and glucose metabolism in PCOS but does not have a direct effect on insulin signalling pathway. Further research is required to elucidate its contribution to the development of in vivo skeletal muscle IR and broader impact in this syndrome. References: (1) Stepto et al., Hum Reprod 2013 Mar;28(3):777–784. (2) Cassar et al., Hum Reprod 2016 Nov;31(11):2619–2631. (3) Corbould et al., Am J Physiol-Endoc 2005 May;88(5):E1047-54. (4) Stepto et al., J Clin Endocrinol Metab, 2019 Nov 1;104(11):5372–5381. (5) Raja-Khan et al., Reprod Sci 2014 Jan;21(1):20–31.

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