Glucose Transporters And Insulin Action Pdf

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Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus

Although diabetes has been identified as a major risk factor for atrial fibrillation, little is known about glucose metabolism in the healthy and diabetic atria. Glucose transport into the cell, the rate-limiting step of glucose utilization, is regulated by the Glucose Transporters GLUTs. We hypothesized that GLUT-4 and -8 translocation to the atrial cell surface will be regulated by insulin and impaired during insulin-dependent diabetes. GLUT protein content was measured by Western blotting in healthy cardiac myocytes and type 1 streptozotocin-induced, T1Dx diabetic rodents. Active cell surface GLUT content was measured using a biotinylated photolabeled assay in the perfused heart. Akt and AS phosphorylation was not impaired in the diabetic atria, suggesting the presence of an intact insulin signaling pathway.

Effects of insulin on glucose transport and glucose transporters in rat heart.

Obesity associated with systemic inflammation induces insulin resistance IR , with consequent chronic hyperglycemia. These pathways promote greater translocation of GLUT4 and consequent glucose uptake by the skeletal muscle. In this sense, the association between autophagy and exercise has also demonstrated a relevant role in the uptake of muscle glucose. Insulin, in turn, uses a phosphoinositide 3-kinase PI3K -dependent mechanism, while exercise signal may be triggered by the release of calcium from the sarcoplasmic reticulum. The objective of this review is to describe the main molecular mechanisms of IR and the relationship between PE and glucose uptake. Insulin resistance IR at target tissues is directly related to chronic subclinical inflammation. When inadequately controlled, IR cause a permanent hyperglycemic status, characterizing the pathophysiology of type 2 diabetes mellitus DM2.

The ability of insulin to stimulate glucose uptake into muscle and adipose tissue is central to the maintenance of whole-body glucose homeostasis. Deregulation of insulin action manifests itself as insulin resistance, a key component of type II diabetes mellitus T2DM. Both forms of diabetes confer an increased risk of major lifelong complications. In the case of insulin resistance, this includes a fivefold increased risk of coronary vascular disease. The need for an effective treatment for both forms of diabetes as well as for the development of early detection methodologies has, therefore, become increasingly important. Yet for this to be possible, we must first understand the mechanism through which insulin regulates glucose uptake and identify the key molecular players involved.

Regulatory Mechanism of Skeletal Muscle Glucose Transport by Phenolic Acids

Perspective Free access Address correspondence to: Jeffrey E. Phone: ; Fax: ; E-mail: jeffrey-pessin uiowa.

The effect of insulin on glucose transport and glucose transporters was studied in perfused rat heart. Glucose transport was measured by the efflux of labelled 3-O-methylglucose from hearts preloaded with this hexose. Insulin stimulated 3-O-methylglucose transport by: a doubling the maximal velocity Vmax ; b decreasing the Kd from 6. Glucose transporters in enriched plasma and microsomal membranes from heart were quantified by the [3H]cytochalasin-B-binding assay.

Signaling pathways in insulin action: molecular targets of insulin resistance

Glucose transporters and insulin action: Some insights into diabetes management

Metrics details. Gaps remain in our understanding of the precise molecular mechanisms by which insulin regulates glucose uptake in fat and muscle cells. Recent evidence suggests that insulin action involves multiple pathways, each compartmentalized in discrete domains. Upon activation, the receptor catalyzes the tyrosine phosphorylation of a number of substrates. One family of these, the insulin receptor substrate IRS proteins, initiates activation of the phosphatidylinositol 3-kinase pathway, resulting in stimulation of protein kinases such as Akt and atypical protein kinase C.

Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysfunction of this process known as insulin resistance causes hyperglycemia, a hallmark of diabetes and obesity. Thus the understanding of the mechanisms underlying this process at the molecular level may give, an insight into the prevention and treatment of these health problems.


Insulin stimulates glucose uptake in muscle and adipose cells primarily by recruiting GLUT4 from an intracellular storage pool to the plasma membrane. Dysf.


GLUT4, the major isoform in insulin-responsive tissue, translocates from an intracellular pool to the cell surface and as such determines insulin-stimulated glucose uptake. However, despite intensive research over 50 years, the insulin-dependent and -independent pathways that mediate GLUT4 translocation are not fully elucidated in any species. Insulin resistance IR is one of the hallmarks of equine metabolic syndrome and is the most common metabolic predisposition for laminitis in horses. IR is characterized by the impaired ability of insulin to stimulate glucose disposal into insulin-sensitive tissues.

Randhawa, Amira Klip; Insulin action on glucose transporters through molecular switches, tracks and tethers. Biochem J 15 July ; 2 : — Glucose entry into muscle cells is precisely regulated by insulin, through recruitment of GLUT4 glucose transporter-4 to the membrane of muscle and fat cells. Work done over more than two decades has contributed to mapping the insulin signalling and GLUT4 vesicle trafficking events underpinning this response. In spite of this intensive scientific research, there are outstanding questions that continue to challenge us today.

Type 2 diabetes mellitus T2DM is one of the most severe public health problems in the world. In recent years, evidences show a commonness of utilization of alternative medicines such as phytomedicine for the treatment of T2DM. Phenolic acids are the most common compounds in non-flavonoid group of phenolic compounds and have been suggested to have a potential to lower the risk of T2DM. Skeletal muscle is the major organ that contributes to the pathophysiology of T2DM.

1 Response
  1. Agate C.

    Whether any of these interactions is actually responsible for the insulin-induced GLUT regulation is yet to be determined. Introduction. Glucose transport in animal.

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