The Key Role of Insulin Resistance in the Cardiometabolic Syndrome

Gill, Harvinder Singh; Mugo, Maryann; Whaley‐Connell, Adam; Stump, Craig S.; Sowers, James R.

doi:10.1097/00000441-200512000-00006

Cited by 68 publications

(49 citation statements)

References 38 publications

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“…Insulin-stimulated glucose transport involves the binding of circulating insulin to the plasma membrane receptor, resulting in phosphorylation of insulin receptor substrate-1 (IRS-1) [1, 2]. The activated IRS-1 molecule interacts with the p85 regulatory subunit of phosphatidylinositol 3-kinase, phosphorylating/activating serine/threonine protein kinase B and other downstream signaling molecules which ultimately results in the translocation of the insulin-sensitive glucose transporter GLUT-4 from intracellular stores to the plasma membrane [37, 38].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperinsulinemia and the compensatory insulin resistance, as seen in patients with cardiometabolic syndrome and type 2 diabetes mellitus, contribute to increases in oxidative stress and inflammation in vasculature, heart, and skeletal muscle [1, 2]. Mounting evidence supports a role for hyperinsulinemia in glomerular filtration barrier injury and subsequent albuminuria observed in type 2 diabetes mellitus [3, 4].…”

Section: Introductionmentioning

confidence: 99%

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Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Whaley‐Connell¹,

DeMarco²,

Lastra³

et al. 2007

Am J Nephrol

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Background/Aim: There is an emerging relationship between insulin resistance/hyperinsulinemia, oxidative stress, and glomerular injury manifesting as albuminuria. HMG-CoA reductase inhibitors (statins) have been shown to reduce oxidative stress in the vasculature as well as albuminuria in animal models and in human studies. The glomerular filtration barrier is emerging as a critical determinant of albumin filtration. We investigated the effects of insulin resistance and rosuvastatin or placebo on the glomerular filtration barrier. Method: Young Zucker obese and Zucker lean rats (6–7 weeks old) were treated with the HMG-CoA reductase inhibitor rosuvastatin (10 mg/kg/day) or placebo for 21 days. Results: In the Zucker obese rats, homeostasis model assessment-insulin resistance index, oxidative markers (NADPH oxidase activity, reactive oxygen species, and urine isoprostane formation), podocyte foot process effacement, and albuminuria were increased as compared with Zucker lean controls, independent of increases in systolic blood pressure. Albuminuria correlated with podocyte foot process effacement (r² = 0.61) and insulin level (r² = 0.69). Rosuvastatin treatment improved albuminuria, filtration barrier indices, and oxidative stress via copper/zinc superoxide dismutase. Conclusions: These data indicate that hyperinsulinemia together with insulin resistance is associated with podocyte injury and albuminuria independent of the systolic blood pressure. Further, rosuvastatin modulates filtration barrier injury and albuminuria and improves oxidative stress measures via copper/zinc superoxide dismutase.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Whaley‐Connell¹,

DeMarco²,

Lastra³

et al. 2007

Am J Nephrol

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“…Based on these results, we speculate that defects in insulin transport across the endothelial layer of skeletal muscle will contribute to insulin resistance. Diabetes 57:828-835, 2008 I nsulin resistance is an important risk factor for type 2 diabetes, as well as other chronic ailments, including cardiovascular disease, hypertension (1)(2)(3), and certain cancers (4). Understanding the cause(s) of insulin resistance is an important goal to improve public health.…”

Section: Research Design and Methods-intramuscular Injections Of Salimentioning

confidence: 99%

Direct Administration of Insulin Into Skeletal Muscle Reveals That the Transport of Insulin Across the Capillary Endothelium Limits the Time Course of Insulin to Activate Glucose Disposal

et al. 2008

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OBJECTIVE-Intravenous insulin infusion rapidly increases plasma insulin, yet glucose disposal occurs at a much slower rate. This delay in insulin's action may be related to the protracted time for insulin to traverse the capillary endothelium. An increased delay may be associated with the development of insulin resistance. The purpose of the present study was to investigate whether bypassing the transendothelial insulin transport step and injecting insulin directly into the interstitial space would moderate the delay in glucose uptake observed with intravenous administration of the hormone. RESEARCH DESIGN AND METHODS-Intramuscular injec-tions of saline (n ϭ 3) or insulin (n ϭ 10) were administered directly into the vastus medialis of anesthetized dogs. Injections of 0.3, 0.5, 0.7, 1.0, and 3.0 units insulin were administered hourly during a basal insulin euglycemic glucose clamp (0.2mU ⅐ minRESULTS-Unlike the saline group, each incremental insulin injection caused interstitial (lymph) insulin to rise within 10 min, indicating rapid diffusion of the hormone within the interstitial matrix. Delay in insulin action was virtually eliminated, indicated by immediate dose-dependent increments in hindlimb glucose uptake. Additionally, bypassing insulin transport by direct injection into muscle revealed a fourfold greater sensitivity to insulin of in vivo muscle tissue than previously reported from intravenous insulin administration.CONCLUSIONS-Our results indicate that the transport of insulin to skeletal muscle is a rate-limiting step for insulin to activate glucose disposal. Based on these results, we speculate that defects in insulin transport across the endothelial layer of skeletal muscle will contribute to insulin resistance. Diabetes 57:828-835, 2008

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“…Adipose tissue is a hormonally active organ synthesising and secreting a number of very active biomolecules, including adipokines [30][31][32][33]. Adipokines are involved in regulating numerous physiologic and pathologic processes through signalling to different organs including the brain, liver and skeletal muscle.…”

Section: Discussionmentioning

confidence: 99%

Przypadek pokrzywki autoimmunologicznej współistniejącej z autoimmunologicznym zespołem wielogruczołowym typu III związanym z chorobą Hashimoto, cukrzycą typu 1 i bielactwem

Kasznicki¹,

Drzewoski²

2014

Endokrynologia Polska

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We present a case of autoimmune polyglandular syndrome type III (APS III) associated with Hashimoto's disease, type 1 diabetes mellitus, vitiligo and autoimmune urticaria. This rare genetic disorder occurs with unknown frequency in the Polish population. It is characterised by endocrine tissue destruction resulting in the malfunction of multiple organs. Several cases of APS III associated with organ-specific autoimmune diseases such as coeliac disease, hypogonadism and myasthenia gravis, as well as organ-nonspecific or systemic autoimmune diseases such as sarcoidosis, Sjögren syndrome, and rheumatoid arthritis have been described. To the best of our knowledge, we here describe the first case of APS III associated with autoimmune thyroiditis, type 1 diabetes mellitus, vitiligo and autoimmune urticaria in an adult patient.

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The Key Role of Insulin Resistance in the Cardiometabolic Syndrome

Cited by 68 publications

References 38 publications

Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Insulin Resistance, Oxidative Stress, and Podocyte Injury: Role of Rosuvastatin Modulation of Filtration Barrier Injury

Direct Administration of Insulin Into Skeletal Muscle Reveals That the Transport of Insulin Across the Capillary Endothelium Limits the Time Course of Insulin to Activate Glucose Disposal

Przypadek pokrzywki autoimmunologicznej współistniejącej z autoimmunologicznym zespołem wielogruczołowym typu III związanym z chorobą Hashimoto, cukrzycą typu 1 i bielactwem

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