Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiogensin-converting enzyme inhibition

Clerk, Lucy H.; Vincent, Michelle A.; Barrett, Eugene J.; Lankford, M.F.; Lindner, Jonathan R.

doi:10.1152/ajpendo.00498.2007

Cited by 75 publications

(71 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dysregulation of AngII activity is a possible link between HS intake and development of vascular dysfunction and insulin resistance [6,9,42,43]. Insulin stimulates microvascular recruitment by a process that is at least partly NO-dependent [16,19].…”

Section: Discussionmentioning

confidence: 99%

A vascular mechanism for high-sodium-induced insulin resistance in rats

et al. 2014

View full text Add to dashboard Cite

Aims/hypothesis High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor linking HS intake to insulin resistance. Methods Sprague Dawley rats were fed a control (0.31% wt/wt NaCl) or HS (8.00% wt/wt NaCl) diet for 4 weeks and subjected to euglycaemic-hyperinsulinaemic clamp (10 mU min) or constant-flow pump-perfused hindlimb studies following an overnight fast. A separate group of HS rats was given quinapril during the dietary intervention and subjected to euglycaemichyperinsulinaemic clamp as above. Results HS intake had no effect on body weight or fat mass or on fasting glucose, insulin, endothelin-1 or NEFA concentrations. However, HS impaired whole body and skeletal muscle glucose uptake, in addition to a loss of insulin-stimulated microvascular recruitment. These effects were present despite enhanced insulin signalling (Akt) in both liver and skeletal muscle. Constant-flow pump-perfused hindlimb experiments revealed normal insulin-stimulated myocyte glucose uptake in HS-fed rats. Quinapril treatment restored insulin-mediated microvascular recruitment and muscle glucose uptake in vivo.Conclusions/interpretation HS-induced insulin resistance is driven by impaired microvascular responsiveness to insulin, and is not due to metabolic or signalling defects within myocytes or liver. These results imply that reducing sodium intake may be important not only for management of hypertension but also for insulin resistance, and highlight the vasculature as a potential therapeutic target in the prevention of insulin resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

A vascular mechanism for high-sodium-induced insulin resistance in rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In response to both exercise and insulin, GLUT4 translocation to the muscle membrane is accelerated (21,74), while the ability to phosphorylate glucose may be unaffected or inhibited by G6P. In addition to the effects on glucose transport, exercise and insulin increase muscle capillary blood flow (12,20,44,87). Together these cellular events predict a shift in the barrier from transport to phosphorylation.…”

Section: Distributed Control Of Blood Glucose Removalmentioning

confidence: 99%

“…Insulin resistance can be associated with deficits in muscle blood flow (11,12,19,89), membrane glucose transport (40,57,104), and intracellular capacity to phosphorylate glucose (7,8,71,102). A corollary to distributed control of MGU is that one or all of these deficits may contribute to insulin resistance.…”

Section: Distributed Control Of Blood Glucose Removalmentioning

confidence: 99%

Four grams of glucose

Wasserman¹

2009

American Journal of Physiology-Endocrinology and Metabolism

338

264

View full text Add to dashboard Cite

Four grams of glucose circulates in the blood of a person weighing 70 kg. This glucose is critical for normal function in many cell types. In accordance with the importance of these 4 g of glucose, a sophisticated control system is in place to maintain blood glucose constant. Our focus has been on the mechanisms by which the flux of glucose from liver to blood and from blood to skeletal muscle is regulated. The body has a remarkable capacity to satisfy the nutritional need for glucose, while still maintaining blood glucose homeostasis. The essential role of glucagon and insulin and the importance of distributed control of glucose fluxes are highlighted in this review. With regard to the latter, studies are presented that show how regulation of muscle glucose uptake is regulated by glucose delivery to muscle, glucose transport into muscle, and glucose phosphorylation within muscle.

show abstract

“…Insulin resistance can be associated with deficits in muscle blood flow (Clerk et al, 2007;Duplain et al, 2001;Inyard et al, 2009;Laakso et al, 1992), membrane glucose transport (Han et al, 1995;Liu et al, 1996;Zierath et al, 1997) and intracellular capacity to phosphorylate glucose (Bonadonna et al, 1996;Braithwaite et al, 1995;Pendergrass et al, 1998;Williams et al, 2001). We delineated the steps that cause the functional impairment in muscle glucose uptake by applying the countertransport method to rats fed a high-fat diet.…”

Section: Control Of Insulin-stimulated Muscle Glucose Influxmentioning

confidence: 99%

The physiological regulation of glucose flux into musclein vivo

Wasserman

Ayala

et al. 2011

Journal of Experimental Biology

137

106

View full text Add to dashboard Cite

Summary Skeletal muscle glucose uptake increases dramatically in response to physical exercise. Moreover, skeletal muscle comprises the vast majority of insulin-sensitive tissue and is a site of dysregulation in the insulin-resistant state. The biochemical and histological composition of the muscle is well defined in a variety of species. However, the functional consequences of muscle biochemical and histological adaptations to physiological and pathophysiological conditions are not well understood. The physiological regulation of muscle glucose uptake is complex. Sites involved in the regulation of muscle glucose uptake are defined by a three-step process consisting of: (1) delivery of glucose to muscle, (2) transport of glucose into the muscle by GLUT4 and (3) phosphorylation of glucose within the muscle by a hexokinase (HK). Muscle blood flow, capillary recruitment and extracellular matrix characteristics determine glucose movement from the blood to the interstitium. Plasma membrane GLUT4 content determines glucose transport into the cell. Muscle HK activity, cellular HK compartmentalization and the concentration of the HK inhibitor glucose 6-phosphate determine the capacity to phosphorylate glucose. Phosphorylation of glucose is irreversible in muscle; therefore, with this reaction, glucose is trapped and the uptake process is complete. Emphasis has been placed on the role of the glucose transport step for glucose influx into muscle with the past assertion that membrane transport is rate limiting. More recent research definitively shows that the distributed control paradigm more accurately defines the regulation of muscle glucose uptake as each of the three steps that define this process are important sites of flux control.

show abstract

Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiogensin-converting enzyme inhibition

Cited by 75 publications

References 37 publications

A vascular mechanism for high-sodium-induced insulin resistance in rats

A vascular mechanism for high-sodium-induced insulin resistance in rats

Four grams of glucose

The physiological regulation of glucose flux into musclein vivo

Contact Info

Product

Resources

About